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Background: Adenovirus are the important pathogen of pediatric severe pneumonia. The aim of this study is to analyze the infection, subtype and distribution of adenovirus in autopsied pulmonary tissue of fatal pneumonia in infants and children, and the relationships between adenovirus infection and respiratory illness in South China. Methods: Nested PCR was performed on DNA extracted from autopsied lung tissue from patients who died of severe pneumonia, and the positive nested PCR products were cloned and sequenced. The adenovirus in autopsied pulmonary tissue was also analyzed by immunohistochemistry assay in a blind way. Results: In the 175 autopsied pulmonary tissues, the positive percentage of adenovirus was 9.14% (16/175) and 2.29% (4/175) detected with nested PCR and immunohistochemistry, respectively. There are three cases of adenovirus serotype 3, twelve cases of adenovirus serotype 4 and one case of serotype 41 determined by sequencing of the cloned positive nested PCR products. Conclusion: Adenovirus is an important cause of severe pneumonia, and these data suggest that adenovirus serotype 4 might be an important pathogen responsible for the fatal pneumonia in Guangzhou, South China. [ABSTRACT FROM AUTHOR]

Acne is a chronic inflammatory disease of pilosebaceous unit, which can be aggravated by hyperkeratosis of the pilosebaceous unit, excessive secretion of sebum and the proliferation of Propionibacterium acnes (P. acnes). Traditional drug treatment methods commonly exhibit drawbacks, including bacterial resistance and poor transdermal permeability, resulting in suboptimal efficacy and recurrent infections. Herein, we designed a dual drug-loaded microneedles patch to deliver ALA and silver nanoparticles for acne treatment. The comprehensive treatment of acne is achieved by utilizing the safe and efficient advantages of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), coupled with the superior antibacterial properties of silver nanoparticles. To enhance drug permeability, dissolving microneedles (DMNs) are employed for targeted and efficient drug delivery. In vitro and in vivo experiments demonstrated that DMNs loaded with both AgNPs and ALA-PDT (ALA/AgNPs@DMNs) have significant antibacterial activity, along with superior drug loading capacity and penetration. The application of ALA/AgNPs@DMNs in treating acne-affected rats alleviates excessive epidermal keratinization, effectively inhibits bacterial growth, and significantly improves acne symptoms. This suggests that the "dissolving microneedle" formulation holds promise for the treatment and management of acne., 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 © 2024 Elsevier B.V. All rights reserved.)

In the electrocatalytic CO 2 reduction reaction (CO 2 RR), the strategic design of a catalytic well capable of regulating the overall confinement effects of catalytic sites holds significant promise for enhancing multiple-electron transfer and C─C coupling efficiency, particularly for the generation of C 2+ products. Here, a series of Cu-salphen-based covalent organic frameworks (COFs) featuring hydroxyl-induced catalytic well are synthesized, which demonstrate successful application in electrocatalytic CO 2 RR to yield multiple-electron transferred products. The meticulously engineered catalytic well, facilitated by multi-hydroxyl groups, manifests robust confinement effects, facilitating selective adsorption, enrichment, and activation of CO 2 , intermediate stabilization, and reduction of energy barriers for electrocatalytic CO 2 RR. Specifically, product selectivity can be finely tuned from CH 4 to C 2 H 4 by modulating the levels of catalytic well, with CuPc-DFP-4OH-Cu exhibiting the most pronounced catalytic well effect, yielding a high 56.86% faradaic efficiency (FE) for C 2 H 4 at -0.7 V, while CuPc-DFP-Cu, with the weakest catalytic well effect, achieves a 75.24% FE for CH 4 at -1.0 V. Notably, the attained FE for C 2 H 4 (56.86%) surpasses that of all reported COFs to date. Complemented by theoretical calculations and in situ tests, this study delves deeply into the pivotal roles of hydroxyl-induced catalytic well with confinement effects., (© 2024 Wiley‐VCH GmbH.)

Purpose: We aimed to evaluate the clinical efficacy of a combined treatment regimen involving terpinen-4-ol (T4O) and eyelid deep cleaning for managing Demodex blepharitis., Methods: In this randomized, open-label trial, 40 patients diagnosed with Demodex blepharitis at the Cornea Specialty Clinic of Hankou Aier Eye Hospital were enrolled. Participants were randomly assigned to either a T4O or a combination treatment group. The T4O group used T4O cleaning wipes exclusively for two months. The combination group used T4O cleaning wipes and underwent deep eyelid cleaning at three scheduled visits (initial, first-, and second-month time points). A final follow-up was conducted one month after completion of treatment (three months after the beginning of treatment). At each visit, we assessed the number of Demodex mites, the ocular surface disease index (OSDI), eyelid margin sign scores, and corneal fluorescein staining scores., Results: After two months of treatment, both the T4O and combination groups exhibited significant reductions in Demodex mite counts of 5.65 ± 6.03 and 7.75 ± 6.91, respectively. The T4O group, however, showed an increase in mite counts one month after ceasing treatment. Conversely, the combination group maintained and enhanced the reduction in mite counts post-treatment, with a significant difference at the third-month follow-up (8.70 ± 6.81 vs. 4.15 ± 6.91, P = 0.043). Although both groups demonstrated overall declines in OSDI scores post-treatment, only the combination group showed significant improvements at the second- and third-month follow-ups. No adverse events were reported in either group., Conclusions: Treatment with T4O wipes for two months significantly reduces Demodex mite counts, although there is a notable risk of mite rebound when treatment is ceased. Combining T4O wipes and eyelid deep cleaning offers a more effective reduction in Demodex mite counts and improvement in ocular symptoms compared to T4O treatment alone., Translational Relevance: The study finds that T4O combined with eyelid deep cleaning is more effective in treating Demodex blepharitis, highlighting the need for appropriate treatment duration and adjunctive therapies.

Pulmonary enteric adenocarcinoma (PEAC), an uncommon variant of lung cancer, presents significant diagnostic challenges due to its overlapping characteristics with colorectal adenocarcinomas. We present a case of a 55-year-old non-smoking female patient diagnosed with PEAC. The patient's initial symptoms included fever, cough, and sputum production, with air space consolidation on CT, leading to an initial diagnosis of pneumonia. Sputum culture after admission showed no growth of bacteria and fungi. Anti-inflammatory therapy was not ideal. Subsequent bronchoscopy with endobronchial ultrasound and biopsy confirmed the diagnosis of PEAC. Gastroscopy and colonoscopy yielded negative results, and a PET/CT scan revealed an FDG-avid lesion in the right middle lobe, with no other significant hypermetabolic gastrointestinal lesions, thereby excluding an extrapulmonary primary gastrointestinal malignancy. The patient was ultimately staged as PEAC (T4N1M0, stage IIIb). She declined anti-tumor therapy and experienced clinical deterioration during follow-up. This case report expands the radiological spectrum of PEAC, adds to the limited literature, and emphasizes the role of 18 F-FDG PET/CT in diagnosing such diseases. It also underscores the importance of a multidisciplinary approach in the management of PEAC., 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 © 2024 Luo, Luo, Luo, Jin and Zeng.)

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies., 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 © 2024. Published by Elsevier Ltd.)

Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms, mediated by ferulate 5-hydroxylase (F5H, CYP84A1), has been considered a recent evolutionary event. F5H uniquely requires the cytochrome b5 protein CB5D as an obligatory redox partner for catalysis. However, it remains unclear how CB5D functionality originated and whether it coevolved with F5H. We reveal here the ancient evolution of CB5D-type function supporting F5H-catalyzed S-lignin biosynthesis. CB5D emerged in charophyte algae, the closest relatives of land plants, and is conserved and proliferated in embryophytes, especially in angiosperms, suggesting functional diversification of the CB5 family before terrestrialization. A sequence motif containing acidic amino residues in Helix 5 of the CB5 heme-binding domain contributes to the retention of CB5D function in land plants but not in algae. Notably, CB5s in the S-lignin-producing lycophyte Selaginella lack these residues, resulting in no CB5D-type function. An independently evolved S-lignin biosynthetic F5H (CYP788A1) in Selaginella relies on NADPH-dependent cytochrome P450 reductase as sole redox partner, distinct from angiosperms. These results suggest that angiosperm F5Hs coopted the ancient CB5D, forming a modern cytochrome P450 monooxygenase system for aromatic ring meta-hydroxylation, enabling the reemergence of S-lignin biosynthesis in angiosperms., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: To evaluate the diagnostic performance of 2-[ 18 F]-fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron-emission tomography (PET)/computed tomography (CT) in TA diagnosis and Takayasu arteritis (TA) activity assessment., Materials and Methods: This retrospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria and undergoing 18 F-FDG PET/CT imaging from October 2010 to July 2022. TA activity was assessed through 18 F-FDG PET/CT (maximum standard uptake value [SUVmax], vascular SUVmax/mean standard uptake value [SUVmean] of liver (SUV ratio), and PET vascular activity score [PETVAS]) using physician global assessment (PGA) as the reference standard, and the results of these assessments were compared against the clinical activity scores (National Institutes of Health [NIH] and Indian Aortitis Disease Activity [ITAS-A] scores), acute-phase reactants (APR), and white blood cell and platelet counts., Results: Twenty 18 F-FDG PET/CT examinations from 19 patients were included in the study, nine were performed in the active phase and 11 in the inactive phase. The involved vessels showed segmental and tubular FDG uptake in the active group. The average SUVmax, SUV ratio, and PETVAS was 6.3 ± 2.7 (range 3.4-12), 4.2 ± 1.7 (range 2.1-7.5), and 22.7 ± 11.2 (range 6-39), respectively, in the active group and 1.7 ± 0.9 (0.9-3.1), 1.1 ± 0.6 (range 0.6-2.4), and 3.5 ± 5.5 (range 0-18), respectively, in the inactive group. The sensitivity, specificity of SUVmax, SUV ratio, and PETVAS for TA activity assessment were 100%, 100%; 100%, 90.9%; and 88.9, 90.9%, respectively. After ROC curve analysis, a new SUVmax cut-off was obtained. Based on the new cut-off value, SUVmax 3.3 and SUV ratio 1.9 had a more perfect assessment performance., Conclusion: 18 F-FDG PET/CT is an alternative imaging technique for TA., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs)., Methods: In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model's performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA)., Results: From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48-65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52-69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53-69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000)., Conclusion: The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility., Critical Relevance Statement: In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment., Key Points: The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility., (© 2024. The Author(s).)

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort., Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness., Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models., Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population., 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 © 2024 Zeng, Qin, Shi, Mu, Huang, Yang, Liu, An and Li.)

Herein, we report the C-H cyanation of indoles via a palladium-catalyzed directed C-CN activation reaction using aryl nitrile as a cyano source. The employment of the phenoxy-oriented group is the key to the cleavage of the C-CN bond. This protocol features a broad substrate scope, good efficiency, and high regioselectivity. Furthermore, the practical application of this protocol was showcased in the late-stage functionalization and synthesis of indole derivatives, which were derived from drugs and natural products, through the process of cyanation.

Introduction: Angiomatoid fibrous histiocytoma (AFH) is a borderline tumor usually affecting the the children or young adults. 18F-Fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) investigations of pulmonary AFH are rare, and there are currently no reports of intense FDG uptake in AFH., Case Report: We report an AFH that occurred in the lung of a 57-year-old woman. She presented with paroxysmal cough and occasional bloodshot sputum. 18FFDG PET/CT revealed a right parahilar nodule with intense FDG-avidity, middle lobe atelectasis, and several bilateral axillary lymph nodes with mild hypermetabolic activity. This patient underwent a right middle lobe lobectomy via video-assisted thoracoscopy. Histopathologically, the diagnosis was pulmonary AFH. She had an uneventful postoperative course, and the bilateral axillary lymph nodes regressed during postoperative follow-up., Conclusions: The clinical presentation and image findings of patients with primary pulmonary AFH may be potential diagnosis pitfalls. The diagnosis of lymph nodes or distant metastases should be approached with caution. To avoid misdiagnosis, biopsy with histological examination and immunohistochemichal staining should be performed as early as possible.

Background: Magnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18 F-fluorodeoxyglucose PET/CT ( 18 F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center., Methods: Patients with SLM who had undergone 18 F-FDG PET/CT and MRI were enrolled. 18 F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18 F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18 F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM., Results: A total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18 F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively., Conclusions: 18 F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-286/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The effects of antibiotic contamination on vegetable safety and the ecological risks of soil after returning livestock and poultry manure to the land require sufficient future attention. Tetracycline antibiotics (TCs) are often detected at high concentrations in livestock manure and vegetable production soils. Recently, pot experiments and field investigation methods have often been used to understand the effects of TCs contamination on the vegetable safety and ecological risks of soil, whereas field experiments are employed less frequently. This study investigated the distribution characteristics of TCs in the soil-vegetable system following manure application using a combination of pot and field experiments. The human health risks of the edible parts of Chinese flowing cabbage were assessed using the health risk quotient method based on the acceptable daily intake (ADI-HQ), and the ecological risks of TCs-contaminated soils were evaluated using the risk quotient method associated with the species sensitivity distribution model (SSD-RQ). The results showed that oxytetracycline (OTC) was the major type of TCs in Chinese flowering cabbage based on both the pot and field experiments. The maximum contents (dry weight) of OTC in the aboveground parts of the Chinese flowering cabbage for the pot and field experiments were 29.25 μg·kg -1 and 45.03 μg·kg -1 , respectively, whereas those of their underground parts were 87.32 μg·kg -1 and 135.44 μg·kg -1 , respectively. Meanwhile, higher contents of TCs were detected in Chinese flowering cabbage collected from the field experiment than those from the pot experiment. OTC was also the major type of TCs in soil from both the pot and field experiments, with their contents up to 604.30 μg·kg -1 and 1013.68 μg·kg -1 , respectively. Higher residual contents of three TCs were detected in soils collected from the field experiment than those from the pot experiment. Under the experimental conditions, with the except that OTC in Chinese flowering cabbage from the field experiment would pose medium health risks (HQ>0.1) to children, the contents of three TCs in other treated Chinese flowering cabbage would pose low health risks (HQ ≤ 0.1) to adults and children. In the pot experiments, three TCs present in Chinese flowering cabbage would pose low health risks (HQ ≤ 0.1) to adults and children. Additionally, the TCs in soils with manure application from the pot and field experiments may have posed both moderate or high levels of ecological risks (HQ>0.1 or HQ>1). Therefore, the effects of antibiotic contamination on vegetable safety and their potential ecological risks on soil following manure fertilization need to be given special attention.

Purpose: To explore and validate the utility of machine learning (ML) methods using a limited sample size to predict changes in visual acuity and keratometry 2 years following corneal crosslinking (CXL) for progressive keratoconus., Methods: The study included all consecutive patients with progressive keratoconus who underwent CXL from July 2014 to December 2020, with a 2 year follow-up period before July 2022 to develop the model. Variables collected included patient demographics, visual acuity, spherical equivalence, and Pentacam parameters. Available case data were divided into training and testing data sets. Three ML models were evaluated based on their performance in predicting case corrected distance visual acuity (CDVA) and maximum keratometry (K max ) changes compared to actual values, as indicated by average root mean squared error (RMSE) and R-squared ( R 2 ) values. Patients followed from July 2022 to December 2022 were included in the validation set., Results: A total of 277 eyes from 195 patients were included in training and testing sets and 43 eyes from 35 patients were included in the validation set. The baseline CDVA (26.7%) and the ratio of steep keratometry to flat keratometry (K 2 /K 1 ; 13.8%) were closely associated with case CDVA changes. The baseline ratio of K max to mean keratometry (K max /K mean ; 20.9%) was closely associated with case K max changes. Using these metrics, the best-performing ML model was XGBoost, which produced predicted values closest to the actual values for both CDVA and K max changes in testing set ( R 2  = 0.9993 and 0.9888) and validation set ( R 2  = 0.8956 and 0.8382)., Conclusion: Application of a ML approach using XGBoost, and incorporation of identifiable parameters, considerably improved variation prediction accuracy of both CDVA and K max 2 years after CXL for treatment of progressive keratoconus., 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 © 2023 Liu, Shen, Wang, Qi and Zeng.)

A highly efficient aerobic denitrifying microbe was isolated from sewage sludge by using a denitrifier enrichment strategy based on decreasing carbon content. The microbe was identified as Pseudomonas mendocina HITSZ-D1 (hereafter, D1). Investigation of the conditions under which D1 grew and denitrified revealed that it performed good growth and nitrate removal performance under a wide range of conditions. In particular, D1 rapidly removed all types of inorganic nitrogen without accumulation of the intermediate products nitrite and nitrous oxide. Overall, D1 showed a total nitrogen removal efficiency >96% at a C/N ratio of 8. The biotransformation modes and fates of three typical types of inorganic nitrogen were also assessed. Moreover, D1 had significantly higher denitrification efficiency and enzyme activities than other aerobic denitrifying microbes (Paracoccus denitrificans, Pseudomonas aeruginosa, and Pseudomonas putida). These results suggest that D1 has great potential for treating wastewater containing high concentrations of nitrogen., 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 © 2023. Published by Elsevier Ltd.)

Objective: Acute lung injury (ALI) is an acute clinical syndrome characterized by uncontrolled inflammation response, which causes high mortality and poor prognosis. The present study determined the protective effect and underlying mechanism of Periplaneta americana extract (PAE) against lipopolysaccharide (LPS)-induced ALI., Methods: The viability of MH-S cells was measured by MTT. ALI was induced in BALB/c mice by intranasal administration of LPS (5 mg/kg), and the pathological changes, oxidative stress, myeloperoxidase activity, lactate dehydrogenase activity, inflammatory cytokine expression, edema formation, and signal pathway activation in lung tissues and bronchoalveolar lavage fluid (BALF) were examined by H&E staining, MDA, SOD and CAT assays, MPO assay, ELISA, wet/dry analysis, immunofluorescence staining and Western blotting, respectively., Results: The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α, IL-6 and IL-1β by suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells. Furthermore, PAE suppressed the neutrophil infiltration, permeability increase, pathological changes, cellular damage and death, pro-inflammatory cytokines expression, and oxidative stress upregulation, which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice., Conclusion: PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties, which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways., (© 2023. Huazhong University of Science and Technology.)

Aminoacyl-tRNA synthetases (aaRSs) are essential components for mRNA translation. Two sets of aaRSs are required for cytoplasmic and mitochondrial translation in vertebrates. Interestingly, TARSL2 is a recently evolved duplicated gene of TARS1 (encoding cytoplasmic threonyl-tRNA synthetase) and represents the only duplicated aaRS gene in vertebrates. Although TARSL2 retains the canonical aminoacylation and editing activities in vitro, whether it is a true tRNA synthetase for mRNA translation in vivo is unclear. In this study, we showed that Tars1 is an essential gene since homozygous Tars1 KO mice were lethal. In contrast, when Tarsl2 was deleted in mice and zebrafish, neither the abundance nor the charging levels of tRNA Thr s were changed, indicating that cells relied on Tars1 but not on Tarsl2 for mRNA translation. Furthermore, Tarsl2 deletion did not influence the integrity of the multiple tRNA synthetase complex, suggesting that Tarsl2 is a peripheral member of the multiple tRNA synthetase complex. Finally, we observed that Tarsl2-deleted mice exhibited severe developmental retardation, elevated metabolic capacity, and abnormal bone and muscle development after 3 weeks. Collectively, these data suggest that, despite its intrinsic activity, loss of Tarsl2 has little influence on protein synthesis but does affect mouse development., Competing Interests: Conflict of interests 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-897/coif). The authors have no conflicts of interest to declare.

Rationale: Sepsis is a severe inflammatory response to infection that leads to long-lasting cognitive impairment and depression after resolution. The lipopolysaccharide (LPS)-induced endotoxaemia model is a well-established model of gram-negative bacterial infection and recapitulates the clinical characteristics of sepsis. However, whether LPS-induced endotoxaemia during adolescence can modulate depressive and anxiety-like behaviours in adulthood remains unclear., Objectives: To determine whether LPS-induced endotoxaemia in adolescence can modulate the stress vulnerability to depressive and anxiety-like behaviours in adulthood and explore the underlying molecular mechanisms., Methods: Quantitative real-time PCR was used to measure inflammatory cytokine expression in the brain. A stress vulnerability model was established by exposure to subthreshold social defeat stress (SSDS), and depressive- and anxiety-like behaviours were evaluated by the social interaction test (SIT), sucrose preference test (SPT), tail suspension test (TST), force swimming test (FST), elevated plus-maze (EPM) test, and open field test (OFT). Western blotting was used to measure Nrf2 and BDNF expression levels in the brain., Results: Our results showed that inflammation occurred in the brain 24 h after the induction of LPS-induced endotoxaemia at P21 but resolved in adulthood. Furthermore, LPS-induced endotoxaemia during adolescence promoted the inflammatory response and the stress vulnerability after SSDS during adulthood. Notably, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and BDNF in the mPFC were decreased after SSDS exposure in mice treated with LPS during adolescence. Activation of the Nrf2-BDNF signalling pathway by sulforaphane (SFN), an Nrf2 activator, ameliorated the effect of LPS-induced endotoxaemia during adolescence on stress vulnerability after SSDS during adulthood., Conclusions: Our study identified adolescence as a critical period during which LPS-induced endotoxaemia can promote stress vulnerability during adulthood and showed that this effect is mediated by impairment of Nrf2-BDNF signalling in the mPFC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Corneal collagen crosslinking (CXL) is an effective treatment for progressive keratoconus. Multiple CXL modalities are clinically available. The present study compared the 1 year outcomes of five types of CXL procedures for progressive keratoconus in a Chinese population using generalized estimating equations (GEE)., Methods: This retrospective study included 239 eyes in 171 patients with keratoconus who underwent CXL and were followed up for 1 year. Five CXL procedures were assessed, including Accelerated Transepithelial CXL, Iontophoresis CXL for 10 min, CXL plus phototherapeutic keratectomy (CXL-plus-PTK), High-Fluence Accelerated CXL, and Accelerated CXL. Patients treated with the Accelerated CXL procedure represented the reference group. Primary outcomes were visual acuity change, spherical equivalence, endothelial cell density, mean keratometry (K mean ), maximum keratometry (K max ), minimum corneal thickness (MCT), and the ABCD Grading System, consisting of A (staging index for ARC; ARC = anterior radius of curvature), B (staging index for PRC, PRC = posterior radius of curvature), and C (staging index for MCT) values 1 year postoperatively compared to baseline. Secondary outcomes were corrected GEE comparisons from each procedure versus the Accelerated CXL group., Results: The Accelerated Transepithelial CXL group had lower performance than the Accelerated CXL group according to K mean and K max . The CXL-plus-PTK group performed significantly better than the reference group as reflected by K max (β = -0.935, P = 0.03). However, the CXL-plus-PTK group did not perform as well for B and C, and the Iontophoresis CXL group performed better for C., Conclusions: The CXL-plus-PTK procedure was more effective than the Accelerated CXL procedure based on K max , and the Iontophoresis CXL procedure performed better on the C value based on the ABCD Grading System., (© 2023. The Author(s).)

Background: Synchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for SMPMNS needs further elucidation., Purpose: This study aimed to evaluate the application of 18 F-FDG PET/CT in patients with SMPMNS., Materials and Methods: The clinical and imaging data of 37 patients with SMPMNS who had undergone 18 F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared., Results: This retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases ( χ 2  = 12.627, p  = 0.000). The maximum standardized uptake value (SUV max ), the SUV max ratio (larger SUV max /smaller SUV max ), and the difference index of SUV max (DISUV max ) [(larger SUV max  - smaller SUV max )/larger SUV max ] of the primary lesions ranged from 0.9 to 41.7 (average = 12.3 ± 7.9), from 0.3 to 26.7 (average = 4.4 ± 6.9), and from 0.0% to 96.3% (average = 50.3% ± 29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency ( κ  = 0.096, p  = 0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency ( κ  = 0.277, p  = 0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity ( p  = 0.02) and CI showing higher specificity ( p  = 0.02)., Conclusions: 18 F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS., 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 Luo, Qi, Jin, Liao, Liu and Zeng.)

Background: Tertiary lymphoid structure (TLS) plays an important role in antitumour immunity, largely reflecting the prognosis. However, its clinical implication in cutaneous squamous cell carcinoma (cSCC) remains unknown., Objectives: To explore the features of TLS in cSCC and its association with clinicopathological characteristics., Methods: Two independent RNA-seq data of cSCC were used to investigate the tumour immune microenvironment, as well as TLS-related chemokines and cytokines. The density and location of TLSs were assessed in a total of 82 cSCC patients, and the clinicopathologic association was examined., Results: Bioinformatics analysis showed that a large amount of immune cell infiltration and significant up-regulation of TLS-related chemokines were observed in cSCC. Histologically, TLSs appeared as highly organized structures in 72 (87.8%) cases with different levels of density and maturation, among which 14 cases were in low-density group and 58 cases were in high-density group. Clinically, the presence of TLS was prominently associated with better degree of histopathological grades and higher level of sun exposure. Furthermore, the presence of intratumoral TLS was associated with lower lymphovascular invasion., Conclusions: TLS is highly organized in cSCC, and the presence of TLS is a positive prognostic factor for cSCC, which will provide a theoretical basis for the future diagnostic and therapeutic value in cSCC., (© 2022 European Academy of Dermatology and Venereology.)

Abies ferreana Bordères & Gaussen 1947 is endemic to China, where it is distributed at 3300-4000 meters in the mountains of Southwest Sichuan and Northwest Yunnan. In this study, the complete chloroplast genome of A. ferreana was reconstructed by de novo assembly using whole-genome sequencing data. The complete chloroplast genome of A. ferreana was 120,049 bp in length with a GC content of 37.9%. A total of 113 genes were identified, including 4 rRNA genes, 35 tRNA genes, and 74 protein-coding genes. Among these, 14 genes contain introns. In the phylogenetic tree with 12 other species of Abies , A. ferreana and Abies fanjingshanensis W. L. Huang et al. 1984 were grouped into the same branch, with a bootstrap value of 100%. The complete chloroplast genome of A. ferreana provides potential genetic resources for further Abies evolutionary and genomic studies., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Here, through single-molecule real-time sequencing, we present a high-quality genome sequence of the Japanese larch (Larix kaempferi), a conifer species with great value for wood production and ecological afforestation. The assembled genome is 10.97 Gb in size, harboring 45,828 protein-coding genes. Of the genome, 66.8% consists of repeat sequences, of which long terminal repeat retrotransposons are dominant and make up 69.86%. We find that tandem duplications have been responsible for the expansion of genes involved in transcriptional regulation and stress responses, unveiling their crucial roles in adaptive evolution. Population transcriptome analysis reveals that lignin content in L. kaempferi is mainly determined by the process of monolignol polymerization. The expression values of six genes (LkCOMT7, LkCOMT8, LkLAC23, LkLAC102, LkPRX148, and LkPRX166) have significantly positive correlations with lignin content. These results indicated that the increased expression of these six genes might be responsible for the high lignin content of the larches' wood. Overall, this study provides new genome resources for investigating the evolution and biological function of conifer trees, and also offers new insights into wood properties of larches., (© 2022 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Objective: The influence of the coronary artery anatomy on the prognosis of patients receiving an arterial switch operation (ASO) is currently controversial, and the risk factors for this operation may change in more complicated patients. This study aimed to investigate the influence of coronary artery anomalies on the in-hospital and post-discharge outcomes of ASO in patients with transposition of the great arteries (TGA) and Taussig-Bing anomaly (TBA)., Methods: We retrospectively reviewed 206 patients who underwent ASO from January 2007 to December 2019. The median age at operation was 33 [interquartile range (IQR): 20-71] days. Median follow-up time was 7.2 years (IQR: 4.0-10.3 years)., Results: Coronary anomalies were present in 86 patients (41.7%), with 9 (4.4%) of them having a single coronary artery. Additional coronary features included intramural courses in 5 (2.4%) patients, ostial stenosis in 1 (0.5%) patient, and accessory coronary artery orifices in 5 (2.4%) patients. There were 32 (15.5%) in-hospital deaths and 8 (4.6%) post-discharge deaths, yielding an overall survival of 81.3%, 80.7% and 79.9% at 1, 5 and 10 years, respectively. Mortality due to ASO has been drastically decreased since 2013. Patients with a single coronary artery had higher rate of in-hospital mortality, but this finding was not statistically significant. The earlier surgical era (OR: 2.756) and a longer cardiopulmonary bypass time (OR: 2.336) were significantly associated with in-hospital mortality, while coronary patterns were not. An intramural coronary artery (HR: 10.034) and a patient age of older than 1 year at the time of ASO (HR: 9.706) were independent predictors of post-discharge mortality., Conclusion: ASO remains the procedure of choice for TGA with coronary anomalies with acceptable in-hospital and post-discharge outcomes in terms of overall survival and freedom of reoperation. However, intramural coronary artery is an independent risk factor for post-discharge mortality. Timely surgery within the 1st year of life helps improve overall midterm survival of ASO., (© 2022. Huazhong University of Science and Technology.)

Aim: To detect an earlier improvement in mild to moderate keratoconus following corneal cross-linking (CXL) with total corneal refractive power (TCRP) using ray tracing method., Methods: A total of 40 eyes of 30 consecutive patients who underwent CXL for progressive keratoconus were retrospectively enrolled. The following keratometric parameters provided by Pentacam HR, including maximum keratometry (Kmax), steepest keratometry (Ksteep), 3 mm zonal TCRP centered over corneal apex (TCRP apex,zone 3 mm), zonal mean keratometry and TCRP centered over corneal cone (Km cone,zone and TCRP cone,zone 1, 2, 3 mm) were evaluated preoperatively and 1, 3, 6, and 12mo postoperatively. Groups 1 and 2 were defined based on Kmax at postoperative 1mo as improved (the initial improvement group) or worsen (the initial deterioration group) compared to the preoperative level., Results: In the overall group, only keratometric parameters based on ray tracing method displayed significant improvement early at 3mo postoperatively, in which TCRP cone,zone 1 mm and 2 mm exhibited the largest flattening (0.57 D and 0.53 D, respectively). In Group 1, only Kmax, Km cone,zone 2 mm and TCRP cone,zone 2 mm showed significant improvement initially at 1mo postoperatively, in which Kmax exhibited the largest improvement (1.05 D), followed by TCRP cone,zone 2 mm (0.82 D). In Group 2, only keratometric parameters based on ray tracing method and Km cone,zone 3 mm showed slight but not significant improvement early at 3mo, in which TCRP cone,zone 3 mm displayed the most improvement (0.19 D), followed by TCRP cone,zone 2 mm (0.15 D)., Conclusion: The findings indicate that a 2 mm zonal TCRP centered over Kmax could earlier detect keratometric improvement by CXL compared to other commonly used parameters in mild to moderate keratoconic eyes., (International Journal of Ophthalmology Press.)

Enzymes are essential components of all biological systems. The key characteristics of proteins functioning as enzymes are their substrate specificities and catalytic efficiencies. In plants, most genes encoding enzymes are members of large gene families. Within such families, the contributions of active site motifs to the functional divergence of duplicate genes have not been well elucidated. In this study, we identified 41 glutaredoxin (GRX) genes in the Populus trichocarpa genome. GRXs are ubiquitous enzymes in plants that play important roles in developmental and stress tolerance processes. In poplar, GRX genes were divided into four classes based on clear differences in gene structure and expression pattern, subcellular localization, enzymatic activity, and substrate specificity of the encoded proteins. Using site-directed mutagenesis, this study revealed that the divergence of the active site motif among different classes of GRX proteins resulted in substrate switches and thus provided new insights into the molecular evolution of these important plant enzymes., (© 2022 Society for Experimental Biology and John Wiley & Sons Ltd.)

The ability to modulate photosynthesis is essential for plants to adapt to fluctuating growing conditions. Populus species show high tolerance to various and highly variable environments. To understand their response strategies against fluctuating environments, this study investigated the morphological and physiological differences of white poplar ( Populus alba ) leaves when grown in a phytotron, glasshouse, and field. Our results show that the palisade cells were elongated in the field, which would enhance intercellular CO 2 exchange. Photosynthetic capacity was the highest in the field leaves, as shown by higher electron transport rates (1.8 to 6.5 times) and carbon assimilation rates (2.7 to 4.2 times). The decrease of PSI acceptor-side limitation and increase of PSI donor-side limitation suggests changes in PSI redox status may contribute to photoprotection. This plasticity of white poplar allows adjusting its structure and photosynthesis under fluctuating conditions, which may partly enable its outstanding tolerance against environmental changes., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2022 Lin et al.)

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Secondary cell wall (SCW) formation is regulated by a multilevel transcriptional regulatory network, in which MYB transcription factors (TFs) play key roles. In woody plants, hundreds of MYB TFs have been identified, most of which have unknown functions in wood SCW biosynthesis. Here, we characterized the function of a Populus MYB gene, PtoMYB10. PtoMYB10 was found to encode an R2R3-MYB TF and exhibit dominant expression in xylem tissues. PtoMYB10 was determined to be located in the nucleus with the ability to activate transcription. Overexpression of PtoMYB10 in Populus resulted in a drastic increase in SCW thickening in xylem fiber cells as well as ectopic deposition of lignin in cortex cells. The expression of genes associated with lignin biosynthesis was induced in PtoMYB10 overexpressing plants, whereas repressed gene expression was found with the anthocyanin biosynthesis pathway. Lignin and anthocyanin are both produced from metabolites of the phenylpropanoid pathway. Accordingly, the anthocyanin content of Populus overexpressing PtoMYB10 decreased by more than 68%. These results indicate that PtoMYB10 can positively regulate xylary fiber SCW thickening, accompanied by the reprogramming of phenylpropanoid metabolism, which redirects metabolic flux from anthocyanin biosynthesis to monolignol biosynthesis., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Backgrounds: Populus and Salix belong to Salicaceae and are used as models to investigate woody plant physiology. The variation of karyotype and nuclear DNA content can partly reflect the evolutionary history of the whole genome, and can provide critical information for understanding, predicting, and potentially ameliorating the woody plant traits. Therefore, it is essential to study the chromosome number (CN) and genome size in detail to provide information for revealing the evolutionary process of Salicaceae., Results: In this study, we report the somatic CNs of seventeen species from eight genera in Salicaceae. Of these, CNs for twelve species and for five genera are reported for the first time. Among the three subfamilies of Salicaceae, the available data indicate CN in Samydoideae is n = 21, 22, 42. The only two genera, Dianyuea and Scyphostegia, in Scyphostegioideae respectively have n = 9 and 18. In Salicoideae, Populus, Salix and five genera closely related to them (Bennettiodendron, Idesia, Carrierea, Poliothyrsis, Itoa) are based on relatively high CNs from n = 19, 20, 21, 22 to n = 95 in Salix. However, the other genera of Salicoideae are mainly based on relatively low CNs of n = 9, 10, 11. The genome sizes of 35 taxa belonging to 14 genera of Salicaceae were estimated. Of these, the genome sizes of 12 genera and all taxa except Populus euphratica are first reported. Except for Dianyuea, Idesia and Bennettiodendron, all examined species have relatively small genome sizes of less than 1 pg, although polyploidization exists., Conclusions: The variation of CN and genome size across Salicaceae indicates frequent ploidy changes and a widespread sharing of the salicoid whole genome duplication (WGD) by the relatives of Populus and Salix. The shrinkage of genome size after WGD indicates massive loss of genomic components. The phylogenetic asymmetry in clade of Populus, Salix, and their close relatives suggests that there is a lag-time for the subsequent radiations after the salicoid WGD event. Our results provide useful data for studying the evolutionary events of Salicaceae., (© 2021. The Author(s).)

The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnection makes it difficult to specify different functions of AAR and UPR. Here, we generated a zebrafish model in which loss of threonyl-tRNA synthetase (Tars) induces angiogenesis dependent on Tars aminoacylation activity. Comparative transcriptome analysis of the tars-mutant and wild-type embryos with/without Gcn2- or Perk-inhibition reveals that only Gcn2-mediated AAR is activated in the tars-mutants, whereas Perk functions predominantly in normal development. Mechanistic analysis shows that, while a considerable amount of eIF2α is normally phosphorylated by Perk, the loss of Tars causes an accumulation of uncharged tRNA Thr , which in turn activates Gcn2, leading to phosphorylation of an extra amount of eIF2α. The partial switchover of kinases for eIF2α largely overwhelms the functions of Perk in normal development. Interestingly, although inhibition of Gcn2 and Perk in this stress condition both can reduce the eIF2α phosphorylation levels, their functional consequences in the regulation of target genes and in the rescue of the angiogenic phenotypes are dramatically different. Indeed, genetic and pharmacological manipulations of these pathways validate that the Gcn2-mediated AAR, but not the Perk-mediated UPR, is required for tars-deficiency induced angiogenesis. Thus, the interconnected AAR and UPR pathways differentially regulate angiogenesis through selective functions and mutual competitions, reflecting the specificity and efficiency of multiple stress response pathways that evolve integrally to enable an organism to sense/respond precisely to various types of stresses., (© 2021. The Author(s).)

Theoretical or numerical progressive collapse analysis is necessary for important civil structures in case of unforeseen accidents. However, currently, most analytical research is carried out under the assumption of material elasticity for problem simplification, leading to the deviation of analysis results from actual situations. On this account, a progressive collapse analysis procedure for truss structures is proposed, based on the assumption of elastoplastic materials. A plastic importance coefficient was defined to express the importance of truss members in the entire system. The plastic deformations of members were involved in the construction of local and global stiffness matrices. The conceptual removal of a member was adopted, and the impact of the member loss on the truss system was quantified by bearing capacity coefficients, which were subsequently used to calculate the plastic importance coefficients. The member failure occurred when its bearing capacity arrived at the ultimate value, instead of the elastic limit. The extra bearing capacity was embodied by additional virtual loads. The progressive collapse analysis was performed by iterations until the truss became a geometrically unstable system. After that, the critical progressive collapse path inside the truss system was found according to the failure sequence of the members. Lastly, the proposed method was verified against both analytical and experimental truss structures. The critical progressive collapse path of the experimental truss was found by the failure sequence of damaged members. The experimental observation agreed well with the corresponding analytical scenario, proving the method feasibility.

To understand host-pathogen interactions and develop effective prevention and control strategies for human adenovirus (HAdV), it is essential to explore the characteristics of HAdV shedding. Hospitalized children <14 years who had severe HAdV pneumonia were tested for HAdV DNA by quantitative real-time PCR in nasopharyngeal aspirate (NPA). A total of 132 children were enrolled, including 102 patients with HAdV type 7 (HAdV-7) infection and 12 patients with HAdV type 3 (HAdV-3) infection. A total of 1372 qualified NPA samples were collected. There was a significant negative correlation between the viral load of HAdV and the course of the disease (Spearman r = -0.547, p = .000). HAdV-7 load decreased at a rate of 0.089 log10 copies/mL per day (95% CI: -0.096 to -0.081; R 2 = 0.332), and the duration of viral shedding was predicted to be 96.9 days (y = 8.624-0.089x). However, HAdV-3 load decreased more quickly (95% CI: - 0.229 to - 0.143; R 2 = 0.403), and the duration of viral shedding was 51.4 days (y = 9.558-0.186x). The median viral load of the HAdV-7 group at weeks 2 and 3, and more than 3 weeks postinfection was higher than that of the HAdV-3 group. No significant differences in the duration of viral shedding were found in different gender, age (>2 vs. ≤2 years), and with or without underlying diseases groups. Viral shedding in children with severe HAdV pneumonia persisted, among which HAdV-7 lasted longer than 3 months and the viral load decreased slowly than HAdV-3., (© 2021 Wiley Periodicals LLC.)

Objective: Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 ( PVT1 ) plays a critical role in the progression of non-small cell lung cancer (NSCLC), there are still many unsolved mysteries remains to be deeply elucidated. This study aimed to find a new underlying mechanism of PVT1 in regulating the tumorigenesis and development of NSCLC., Materials and Methods: In this experimental study, Quantitative reverse transcription polymerase chain reaction (qRTPCR) was used to profile the expression of PVT1 in NSCLC tissues and cells. The effects of PVT1 on cell growth, migration and invasion were detected by colony formation assay, Matrigel-free transwell and Matrigel transwell assays, respectively. Changes of the key protein expression in Hippo and NOTCH signaling pathways, as well as epithelialmesenchymal transition (EMT) markers, were analyzed using western blot. Interaction of PVT1 with enhancer of zeste homolog 2 (EZH2) was verified by RNA pull-down, and their binding to the downstream targets was detected by Chromatin Immunoprecipitation (ChIP) assays., Results: These results showed that PVT1 was up-regulated in NSCLC tissue and cell lines, promoting NSCLC cell proliferation, migration and invasion. Knockdown of PVT1 inhibited the expression of Yes-associated protein 1 (YAP1) and NOTCH1 signaling activation. Further, we have confirmed that PVT1 regulated expression of YAP1 through EZH2-mediated miR-497 promoter methylation resulting in the inhibition of miR-497 transcription and its target YAP1 upregulation, and finally NOTCH signaling pathway was activated, which promoted EMT and invasion and metastasis., Conclusion: These results suggested that lncRNA PVT1 promotes NSCLC metastasis through EZH2-mediated activation of Hippo/NOTCH1 signaling pathways. This study provides a new opportunity to advance our understanding in the potential mechanism of NSCLC development., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Bile acids in host intestine activate larvae of tapeworms and facilitate its invasion. However, the mechanism underlying this process is poorly understood. In order to better understand responses of tapeworms to host biles, we used RNA-Seq profiling method to study the transcriptomes of Cysticercus Pisiformis (larvae of Taenia Pisiformis) after host bile acid treatment. A total of 338.32 million high-quality clean reads were obtained by Illumina Hiseq platform. Totally, 62,009 unigenes were assembled, 38,382 of which were successfully annotated to known databases. A total of 9324 unigenes were identified as differentially expressed genes (DEGs), of which 5380 and 3944 genes were up- and down-regulated in the group treated with bile acids, respectively. Gene Ontology analysis revealed that biosynthesis and energy metabolism potential were significantly strengthened after host bile treatment in C. pisiformis. Similarly, KEGG pathway analysis revealed an enrichment of pathways related to lipid metabolism and carbohydrate metabolism. Among them, 'AMPK signaling pathway' which is critical in balancing cellular energy, was significantly enriched after bile acids activation. In addition, pathways of 'Fatty acid biosynthesis', 'Fatty acid elongation', 'Starch and sucrose metabolism', and 'glycolysis gluconeogenesis' were also significantly changed after bile acid treatment. qRT-PCR analysis confirmed the differential abundances of some key genes in these pathways. Our data suggest that host bile acids remarkably promote the pathways of energy metabolism of this parasite and regulate the genes involved in balancing lipid metabolism and carbohydrate metabolism. These findings provide new insights on the lifecycle of Taenia parasites., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The current study was focused on preparing curcumin (CUR) supersaturated self-nano-emulsion (PI-CUR-SNEDDS) using hydrophilic polymer and to study the influence of polymer precipitation inhibitor on the physicochemical and biopharmaceutical properties of the PI-CUR-SNEDDS., Methods: PI-CUR-SNEDDS were prepared using hydrophilic polymer in order to maintain the supersaturation of CUR in nano-emulsion solution, artificial gastrointestinal fluid (AGF), and the precipitates formed, and characterised by in vitro dispersion tests, in vitro intestinal absorption and in vivo pharmacokinetic and compared with CUR-SNEDDS., Key Findings: PI-CUR-SNEDDS prepared with 2% hydroxypropyl methylcellulose 55-60 (HPMC55-60) as precipitation inhibitor (PI) significantly improved the viscosity, physical stability and CUR's equilibrium solubility of nanoemulsion. HPMC55-60 and CUR interact in AGF through intermolecular interactions, form hydrogen bonds, and produce amorphous precipitates. Compared with CUR-SNEDDS, the proportion of CUR in the hydrophilic phase increased by about 3-fold, and apparent permeability coefficient (Papp) in duodenum, jejunum, ileum, and colon increased by 2.30, 3.65, 1.54 and 2.08-fold, respectively, and the area under the plasma concentration-time curve0-12h of PI-CUR-SNEDDS also increased by 3.50-fold., Conclusions: Our results suggested that HPMC55-60 maintained the CUR supersaturation state by forming hydrogen bonds with CUR, increasing the solution's viscosity and drug solubilisation, thus improving the absorption and bioavailability of CUR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We isolated a novel lectin (AHL) from Artocarpus hypargyreusHance and showed its immunomodulatory activities. In this study, the amino acid sequence of AHL was determined by cDNA sequencing. AHL cDNA (875bp) contains a 456-bp open reading frame (ORF), which encodes a protein with 151 amino acids. AHL is a new member of jacalin-related lectin family (JRLs), which share high sequence similarities to KM+ and Morniga M, and contain the conserved carbohydrate binding domains. The antitumor activity of AHL was also explored using Jurkat T cell lines. AHL exhibits a strong binding affinity to cell membrane, which can be effectively inhibited by methyl-α-D-galactose. AHL inhibits cell proliferation in a time- and dose-dependent manner through apoptosis, evidenced by morphological changes, phosphatidylserine externalization, poly ADP-ribose polymerase (PARP) cleavage, Bad and Bax up-regulation, and caspase-3 activation. We further showed that the activation of ERK and p38 signaling pathways is involved for the pro-apoptotic effect of AHL., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Chronic refractory wounds are generally caused by local tissue defects and necrosis, and they are characterized by delayed wound healing as well as high recurrence, which seriously affects life quality. However, effective therapeutics to treat wounds are currently unavailable. Therapy primarily aims to accelerate generation of granulation tissue and decrease recurrence. The pathogenesis of chronic refractory wounds is closely related to multiple complex signaling pathways and a series of cytokines. Among these signaling pathways, TGF-β/Smad7 axis plays a critical role. Specifically, Smad7 is an antagonist of TGF-β that inhibits activation of TGF-β. Moreover, Smad7 promotes wound healing by regulating cytokines and controlling growth, differentiation and apoptosis of cells, which may be exploited to cure the disease. This review aims to reveal the exact functions and mechanisms of Smad7 in regulation of wound healing.

A novel nanocomposite poly(ethylene-co-vinyl acetate) (EVA) film with controlled in vitro release of iprodione (ID) was prepared. Chitosan (CS) was used as the reinforcement which enhances the water and oxygen permeability of films. ID loaded poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) (IPP) micelles were used as the drug carrier which endows the films with antifungal and controlled release ability. IPP micelles with spherical shape and uniform size were obtained, and the maximum encapsulation efficacy (EE) was 91.17 ± 5.03% by well controlling the feeding amount of ID. Incorporation CS could improve the oxygen and moisture permeability of films, and the maximum oxygen permeability (OP) and water vapor transmission rate (WVTR) were 477.84 ± 13.03 cc/(m 2 ·d·0.1 MPa) and 8.60 ± 0.25 g m -2 d -1 , respectively. After loading IPP micelles, the films showed an improved antifungal ability and temperature-sensitive drug release behavior, and were found to enhance the quality of grapes by pre-harvest spraying., 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 © 2020 Elsevier Ltd. All rights reserved.)

Aminoacyl-tRNA synthetases (aaRSs) are ubiquitously expressed, essential enzymes, synthesizing aminoacyl-tRNAs for protein synthesis. Functional defects of aaRSs frequently cause various human disorders. Human KARS encodes both cytosolic and mitochondrial lysyl-tRNA synthetases (LysRSs). Previously, two mutations (c.1129G>A and c.517T>C) were identified that led to hearing impairment; however, the underlying biochemical mechanism is unclear. In the present study, we found that the two mutations have no impact on the incorporation of LysRS into the multiple-synthetase complex in the cytosol, but affect the cytosolic LysRS level, its tertiary structure, and cytosolic tRNA aminoacylation in vitro. As for mitochondrial translation, the two mutations have little effect on the steady-state level, mitochondrial targeting, and tRNA binding affinity of mitochondrial LysRS. However, they exhibit striking differences in charging mitochondrial tRNA Lys , with the c.517T>C mutant being completely deficient in vitro and in vivo. We constructed two yeast genetic models, which are powerful tools to test the in vivo aminoacylation activity of KARS mutations at both the cytosolic and mitochondrial levels. Overall, our data provided biochemical insights into the potentially molecular pathological mechanism of KARS c.1129G>A and c.517T>C mutations and provided yeast genetic bases to investigate other KARS mutations in the future.

Aim: To observe the characteristics of iridociliary cysts in myopic patients and evaluate the influences on the position and safety of implantable collamer lens (ICL) after surgery., Methods: Totally 270 eyes of 135 patients who underwent ICL surgery for the corrections of myopia were included in this study. Preoperative and postoperative morphology of iridociliary cysts were observed in ultrasonic biomicroscopy (UBM) image., Results: A total of 138 iridociliary cysts were found in 88 eyes of 50 patients among 270 eyes of 135 patients before surgery (37%). Twenty-five patients had cysts in one eye (50%) and 25 had cysts in both eyes (50%). The prevalence of iridociliary cysts was negatively correlated with age, but no gender difference ( P >0.05). The incidence of iridociliary cysts was much less in eyes with myopia greater than -9.00 D ( P <0.05). The diameter of the largest cyst was 1.96 mm and the smallest cyst was 0.24 mm, with a majority within the range of 0.5 to 1.0 mm. Most of the cysts were located in the inferior temporal quadrant. One year after ICL implantation, 51 iridociliary cysts (37%) remained unchanged, 47 cysts (34%) decreased in size, and 40 cysts (29%) disappeared. Most of cysts that changed after surgery were smaller than 1.0 mm ( P <0.05) and located in the nasal and temporal sides around the haptics of implantable lens. All the ICL were in their original position., Conclusion: Iridociliary cysts are commonly seen in myopic eyes. The cysts have no impact on the safety of ICL surgery. Some cysts may decrease in size or disappear after ICL implantation., (International Journal of Ophthalmology Press.)

Pollen wall consists of several complex layers which form elaborate species-specific patterns. In Arabidopsis, the transcription factor ABORTED MICROSPORE (AMS) is a master regulator of exine formation, and another transcription factor, TRANSPOSABLE ELEMENT SILENCING VIA AT-HOOK (TEK), specifies formation of the nexine layer. However, knowledge regarding the temporal regulatory roles of TEK in pollen wall development is limited. Here, TEK-GFP driven by the AMS promoter was prematurely expressed in the tapetal nuclei, leading to complete male sterility in the pAMS:TEK-GFP (pat) transgenic lines with the wild-type background. Cytological observations in the pat anthers showed impaired callose synthesis and aberrant exine patterning. CALLOSE SYNTHASE5 (CalS5) is required for callose synthesis, and expression of CalS5 in pat plants was significantly reduced. We demonstrated that TEK negatively regulates CalS5 expression after the tetrad stage in wild-type anthers and further discovered that premature TEK-GFP in pat directly represses CalS5 expression through histone modification. Our findings show that TEK flexibly mediates its different functions via different temporal regulation, revealing that the temporal regulation of TEK is essential for exine patterning. Moreover, the result that the repression of CalS5 by TEK after the tetrad stage coincides with the timing of callose wall dissolution suggests that tapetum utilizes temporal regulation of genes to stop callose wall synthesis, which, together with the activation of callase activity, achieves microspore release and pollen wall patterning., Competing Interests: The authors have declared that no competing interests exist.

N 6-Threonylcarbamoyladenosine (t6A) is a universal tRNA modification essential for translational accuracy and fidelity. In human mitochondria, YrdC synthesises an l-threonylcarbamoyl adenylate (TC-AMP) intermediate, and OSGEPL1 transfers the TC-moiety to five tRNAs, including human mitochondrial tRNAThr (hmtRNAThr). Mutation of hmtRNAs, YrdC and OSGEPL1, affecting efficient t6A modification, has been implicated in various human diseases. However, little is known about the tRNA recognition mechanism in t6A formation in human mitochondria. Herein, we showed that OSGEPL1 is a monomer and is unique in utilising C34 as an anti-determinant by studying the contributions of individual bases in the anticodon loop of hmtRNAThr to t6A modification. OSGEPL1 activity was greatly enhanced by introducing G38A in hmtRNAIle or the A28:U42 base pair in a chimeric tRNA containing the anticodon stem of hmtRNASer(AGY), suggesting that sequences of specific hmtRNAs are fine-tuned for different modification levels. Moreover, using purified OSGEPL1, we identified multiple acetylation sites, and OSGEPL1 activity was readily affected by acetylation via multiple mechanisms in vitro and in vivo. Collectively, we systematically elucidated the nucleotide requirement in the anticodon loop of hmtRNAs, and revealed mechanisms involving tRNA sequence optimisation and post-translational protein modification that determine t6A modification levels., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)