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Huge annual consumption of thermoplastics results in the generation of large amounts of waste after their service life. Currently, the most popular recycling method based on mechanically melt-reprocessing deteriorates the material performance and is economically unattractive, which makes it unviable to be implemented in large scale. Herein, we present a chemical upcycling strategy that can transform dimethylglyoxime-urethane based thermoplastic waste into thermoset product with superior mechanical properties and higher economic values than the initial one. It is found that the dimethylglyoxime-urethane moiety has dynamic nature, endowing the material with open-loop upcycling ability. By removing the dimethylglyoxime segment via a simple sublimation process, the material structure is transformed from linear molecular into crosslinked network. More interestingly, the transformation is reversible, and the regenerated crosslinked network can be transformed back to linear molecule by returning the removed dimethylglyoxime segment to the material, which means the upcycled product can be recycled again after its service life. Our linear/crosslinked transformation strategy provide a new option for recycling thermoplastic waste., (© 2024 Wiley-VCH GmbH.)

The efficient and reversible separation of radioactive Xe/Kr during spent fuel reprocessing is important and challenging for the rapid development of nuclear energy. In this study, we firstly report a strategy of applying an electric field on the solid adsorbent borophene to realize efficient and switchable Xe/Kr separation via a density functional theory (DFT) investigation. Based on the calculational results, the adsorption energies for Xe and Kr on borophene without an electric field are -0.25 eV and -0.18 eV, respectively, indicating that Xe and Kr can only form weak adsorption on borophene. However, by applying an electric field (0.006 a.u.) to the systems, the adsorption energies for Xe and Kr on borophene are -0.98 eV and -0.47 eV, respectively, which shows that the interaction between Xe and borophene has increased dramatically compared with that of Kr, so Xe can be separated from radioactive Xe/Kr mixtures. What's more, when the electric field is removed, desorption of Xe from the surface of borophene is exothermic without an energy barrier. The adsorbent is recyclable. In summary, this theoretical study provides novel information for experimental researches, the highly efficient Xe/Kr separation can be controlled by turning on/off the applied electric field., (© 2024 Wiley-VCH GmbH.)

Infigratinib, an FGFR1-3 selective oral tyrosine kinase inhibitor, has shown clinical activity in cancers with FGFR alterations. The pharmacokinetics (PK) of infigratinib and its major metabolites have been characterized in global populations. This study examined the PK profile of infigratinib and its metabolites in Chinese patients. In this phase II, open-label, single-arm study in China, patients with advanced gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ) harboring FGFR2 gene amplification received 125 mg infigratinib orally once daily in a "3 weeks on, 1 week off" schedule for 28-day cycles. Plasma PK parameters were calculated with a non-compartmental model. Data were available from 21 patients (19 GC and two GEJ). After a single dose, peak infigratinib plasma concentration was reached at a median time of 3.1 h, with geometric mean C max of 85.9 ng/mL and AUC 0-t of 637 h*ng/mL. After 21-day dosing, geometric mean infigratinib C max,ss of 204 ng/mL was reached at a median of 4.0 h; geometric mean AUC 0-24,ss was 3060 h*ng/mL. The geometric mean R ac , Cmax (%CV) and R ac , AUC0-24 (%CV) of infigratinib was 2.5 (113.8) and 5.1 (138.2), respectively. A steady state of infigratinib was reached after continuous dosing for 15 days. The metabolites accounting for >10% of infigratinib were BHS697 and CQM157. The PK profiles of infigratinib and its metabolites in Chinese patients with GC or GEJ were largely consistent with known PK profiles of infigratinib from global populations., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL., Competing Interests: Conflicts of Interest Disclosure The authors have nothing to disclose., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

In Northwest China, the highway infrastructure often faces challenges due to the widespread presence of subgrade soil. This soil undergoes significant changes in performance under cyclic loading and freeze-thaw cycles. To effectively design and construct highways in these regions, it is crucial to understand the impact of various factors on the deformation characteristics and mechanical properties of subgrade soil. This study aims to investigate the influence of freeze-thaw cycles, water content, confining pressure, and loading rate on the deformation behavior and mechanical properties of subgrade soil under cyclic loading conditions. Experimental tests were conducted to analyze the deformation characteristics and mechanical properties of the subgrade soil. The test results revealed the following: 1) Dynamic loading leads to a noticeable decrease in the strength of subgrade soil, resulting in a softening effect on the stress-strain curve. The cumulative strain of the soil is positively correlated with the number of freeze-thaw cycles and water content, while negatively correlated with confining pressure. The final cumulative strain remains below 1%. 2) The failure stress of subgrade soil decreases exponentially with an increase in freeze-thaw cycles, dropping from 224.52 kPa to 196.76 kPa. 3) An increase in water content linearly decreases the failure stress of subgrade soil, ranging from 377.1 kPa to 151.5 kPa. 4) Confining pressure exhibits a linearly increasing relationship with the failure stress of subgrade soil, ranging from 151.6 kPa to 274.5 kPa. 5) The failure stress of subgrade soil demonstrates a linear increase with the loading rate, ranging from 200.46 kPa to 210.62 kPa. These findings provide valuable insights for the design and construction of highways in seasonal frozen areas. They also offer guidance for preventing and mitigating subgrade freeze-thaw issues in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li 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.)

Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C → T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria., (© 2024. The Author(s).)

Accurate and intelligent identification of rare and endangered individuals of flagship wildlife species, such as Amur tiger ( Panthera tigris altaica ), is crucial for understanding population structure and distribution, thereby facilitating targeted conservation measures. However, many mathematical modeling methods, including deep learning models, often yield unsatisfactory results. This paper proposes an individual recognition method for Amur tigers based on an improved InceptionResNetV2 model. Initially, the YOLOv5 model is employed to automatically detect and segment facial, left stripe, and right stripe areas from images of 107 individual Amur tigers, achieving a high average classification accuracy of 97.3%. By introducing a dropout layer and a dual-attention mechanism, we enhance the InceptionResNetV2 model to better capture the stripe features of individual tigers at various granularities and reduce overfitting during training. Experimental results demonstrate that our model outperforms other classic models, offering optimal recognition accuracy and ideal loss changes. The average recognition accuracy for different body part features is 95.36%, with left stripes achieving a peak accuracy of 99.37%. These results highlight the model's excellent recognition capabilities. Our research provides a valuable and practical approach to the individual identification of rare and endangered animals, offering significant potential for improving conservation efforts.

Background: The robustness and credibility of RT-qPCR results are critically dependent on the selection of suitable reference genes. However, the mineralization of the extracellular matrix can alter the intracellular tension and energy metabolism within cells, potentially impacting the expression of traditional reference genes, namely Actb and Gapdh., Objective: To methodically identify appropriate reference genes for research focused on mouse cementoblast mineralization., Materials and Methods: Time-series transcriptomic data of mouse cementoblast mineralization were used. To ensure expression stability and medium to high expression levels, three specific criteria were applied to select potential reference genes. The expression stability of these genes was ranked based on the DI index (1/coefficient of variation) to identify the top six potential reference genes. RT-qPCR validation was performed on these top six candidates, comparing their performance against six previously used reference genes (Rpl22, Ppib, Gusb, Rplp0, Actb, and Gapdh). Cq values of these 12 genes were analyzed by RefFinder to get a stability ranking., Results: A total of 4418 (12.27%) genes met the selection criteria. Among them, Rab5if, Chmp4b, Birc5, Pea15a, Nudc, Supt4a were identified as candidate reference genes. RefFinder analyses revealed that two candidates (Birc5 and Nudc) exhibited superior performance compared to previously used reference genes., Limitations: RefFinder's stability ranking does not consider the influence of primer efficiency., Conclusions and Implications: We propose Birc5 and Nudc as candidate reference genes for RT-qPCR studies investigating mouse cementoblast mineralization and cementum repair., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Orthodontic Society. 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.)

Objective: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML)., Methods: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry., Results: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner ( r 24 h =0.7592, r 48 h =0.9456, and r 72 h =0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner ( r =0.9057 in 2.5 μmol/L group, r =0.9897 in 5 μmol/L group and r =0.9994 in 10 μmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner ( r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G 0 /G 1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G 0 /G 1 phase was increased and the cell synthesis was decreased., Conclusion: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.

Phosphorus concentration on the surface of seawater varies greatly with different environments, especially in coastal. The molecular mechanism by which cyanobacteria adapt to fluctuating phosphorus bioavailability is still unclear. In this study, transcriptomes and gene knockouts were used to investigate the adaptive molecular mechanism of a model coastal cyanobacterium Synechococcus sp. PCC 7002 during periods of phosphorus starvation and phosphorus recovery (adding sufficient phosphorus after phosphorus starvation). The findings indicated that phosphorus deficiency affected the photosynthesis, ribosome synthesis, and bacterial motility pathways, which recommenced after phosphorus was resupplied. Even more, most of the metabolic pathways of cyanobacteria were enhanced after phosphorus recovery compared to the control which was kept in continuous phosphorus replete conditions. Based on transcriptome, 54 genes potentially related to phosphorus-deficiency adaptation were selected and knocked out individually or in combination. It was found that five mutants showed weak growth phenotype under phosphorus deficiency, indicating the importance of the genes ( A0076 , A0549-50 , A1094 , A1320 , A1895 ) in the adaptation of phosphorus deficiency. Three mutants were found to grow better than the wild type under phosphorus deficiency, suggesting that the products of these genes ( A0079 , A0340 , A2284-86 ) might influence the adaptation to phosphorus deficiency. Bioinformatics analysis revealed that cyanobacteria exposed to highly fluctuating phosphorus concentrations have more sophisticated phosphorus acquisition strategies. These results elucidated that Synechococcus sp. PCC 7002 have variable phosphorus response mechanisms to adapt to fluctuating phosphorus concentration, providing a novel perspective of how cyanobacteria may respond to the complex and dynamic environments., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00244-y., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2024.)

Background: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association., Methods: Essential hypertensive patients (n = 292) aged 18-83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI ≤ 0.32, n = 146) and Group II (LASI > 0.32, n = 146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI., Results: Age, BMI, SBP, HbA1c, CRP, and NLR were significantly greater in Group II than in Group I (P < 0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') and lower LA reservoir, conduit, and booster pump strains than Group I (P < 0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%., Conclusions: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

In the crystal structure of the title compound, {[Co(C 11 H 9 NSO 5 )(C 10 H 9 N 3 )]0.5C 3 H 7 NO·H 2 O} n or {[Co(dmtb)(dpa)]·0.5DMF·H 2 O} n (dmtb 2- = 5-[(di-meth-yl-amino)-thioxometh-oxy]-1,3-benzene-dicarboxyl-ate and dpa = 4,4'-di-pyridyl-amine), an assembly of periodic [Co(C 11 H 9 NSO 5 )(C 10 H 9 N 3 )] n layers extending parallel to the bc plane is present. Each layer is constituted by distorted [CoO 4 N 2 ] octa-hedra, which are connected through the μ 2 -coordination modes of both dmtb 2- and dpa ligands. Occupationally disordered water and di-meth-yl-formamide (DMF) solvent mol-ecules are located in the voids of the network to which they are connected through hydrogen-bonding inter-actions., (© Qin et al. 2024.)

Purpose: DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory., Experimental Design: We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls., Results: Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS., Conclusions: The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening., (©2024 American Association for Cancer Research.)

The rotational speed standard device that can carry loads is the key device for calibrating passive rotational speed sensors. The rotor of the passive rotational speed sensor is connected to the rotor of the standard speed device through a coupling, and the standard reference speed is provided by the standard device. Due to the rotor eccentricity, the unbalanced force of the rotor occurs, and it can not only affect the rotational speed accuracy but can also damage the mechanical bearings of the standard speed device. To solve this issue, a method for suppressing the unbalanced force of the speed standard device based on an active magnetic bearing (AMB) force compensation system is proposed. First, the overall structure of the system is briefly introduced. Then, the force feedback control system model with the AMB as the force actuator is established, and a PI controller is designed to achieve the disturbed force control. Finally, a semi-physical simulation experimental platform is built to verify the effectiveness of the proposed method. The experimental results show that the AMB force compensation system can reduce 84.4%, 81.6%, and 79.8% of the unbalanced vibration force at the frequency of 30 Hz, 90 Hz, and 150 Hz, respectively.

In light of the important biological activities and widespread applications of organic disulfides, dithiocarbamates, xanthates, thiocarbamates and thiocarbonates, the continual persuit of efficient methods for their synthesis remains crucial. Traditionally, the preparation of such compounds heavily relied on intricate multi-step syntheses and the use of highly prefunctionalized starting materials. Over the past two decades, the direct sulfuration of C-H bonds has evolved into a straightforward, atom- and step-economical method for the preparation of organosulfur compounds. This review aims to provide an up-to-date discussion on direct C-H disulfuration, dithiocarbamation, xanthylation, thiocarbamation and thiocarbonation, with a special focus on describing scopes and mechanistic aspects. Moreover, the synthetic limitations and applications of some of these methodologies, along with the key unsolved challenges to be addressed in the future are also discussed. The majority of examples covered in this review are accomplished via metal-free, photochemical or electrochemical approaches, which are in alignment with the overraching objectives of green and sustainable chemistry. This comprehensive review aims to consolidate recent advancements, providing valuable insights into the dynamic landscape of efficient and sustainable synthetic strategies for these crucial classes of organosulfur compounds., (© 2024 Wiley-VCH GmbH.)

Objective: To investigate the effect of early pulmonary rehabilitation (PR) training on the improvement of respiratory function in patients with acute respiratory distress syndrome (ARDS) after weaning of invasive mechanical ventilation in the intensive care unit (ICU)., Methods: The retrospective cohort research method was used. The clinical information of adult patients with ARDS receiving invasive mechanical ventilation admitted to the ICU of Qingdao Municipal Hospital from January 2019 to March 2023 was collected. The patients were divided into a control group and an observation group according to off-line training program. The control group received traditional training after weaning, and the observation group received the early PR training after weaning. Other treatments and nursing were implemented according to the routine of the ICU. The scores of the short physical performance battery (SPPB) on day 3-day 6 of the weaning training, respiratory muscle strength, level of interleukin-6 (IL-6), number of aspirations of sputum after weaning, length of stay after weaning, rehospitalization rate within 6 months after discharge, and pulmonary function indicators at discharge and 3 months after discharge [peak expiratory flow (PEF), forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and vital capacity (VC)] of the two groups of patients were compared. The Kaplan-Meier survival curve was drawn to analyze the cumulative survival rate of patients 6 months after discharge., Results: A total of 50 of which 25 cases received the traditional training after weaning, 25 cases received the early PR training after weaning. There was no significant difference in gender, age, acute physiology and chronic health evaluation II (APACHE II), oxygenation index upon admission, etiological diagnosis of ARDS upon admission, time of invasive ventilation, mode of invasive mechanical ventilation, pulmonary function indicators at discharge, and other baseline data of the two groups. The SPPB questionnaire scores and respiratory muscle strength in both groups were increased gradually with the extended offline training time, the serum level of IL-6 in both groups were descend gradually with the extended offline training time, especially in the observation group [SPPB questionnaire score in the observation group were 7.81±0.33, 8.72±0.53, 9.44±0.31, 10.57±0.50, while in the control group were 7.74±0.68, 8.73±0.37, 8.72±0.40, 9.33±0.26, effect of time: F = 192.532, P = 0.000, effect of intervention: F = 88.561, P = 0.000, interaction effect between intervention and time: F = 24.724, P = 0.000; respiratory muscle strength (mmHg, 1 mmHg≈0.133 kPa) in the observation group were 123.20±24.84, 137.00±26.47, 149.00±24.70, 155.40±29.37, while in the control group were 129.00±20.34, 126.00±24.01, 132.20±25.15, 138.60±36.67, effect of time: F = 5.926, P = 0.001, effect of intervention: F = 5.248, P = 0.031, interaction effect between intervention and time: F = 3.033, P = 0.043; serum level of IL-6 in the observation group were 80.05±6.81, 74.76±9.33, 63.66±10.19, 56.95±4.72, while in the control group were 80.18±7.21, 77.23±9.78, 71.79±10.40, 66.51±6.49, effect of time: F = 53.485, P = 0.000, effect of intervention: F = 22.942, P = 0.000, interaction effect between intervention and time: F = 3.266, P = 0.026]. Compared with the control group, the number of aspirations of sputum after weaning of patients in the observation group significantly decreased (number: 22.46±1.76 vs. 27.31±0.90), the length of ICU stay after weaning significantly became shorter (days: 6.93±0.95 vs. 8.52±2.21), and the rehospitalization rate within 6 months after discharge significantly decreased [20.00% (5/25) vs. 48.00% (12/25)]. There were significant differences. The pulmonary function indicators 3 months after discharge of two groups of patients significantly increased compared with those at discharge and those of the observation group were significantly higher than those of the control group [PEF (L/min): 430.20±95.18 vs. 370.00±108.44, FEV1/FVC ratio: 0.88±0.04 vs. 0.82±0.05, VC (L): 3.22±0.72 vs. 2.74±0.37, all P < 0.05]. The Kaplan-Meier survival curve showed that the cumulative survival rate of patients 6 months after discharge of patients in the observation group was significantly higher than that of patients in the control group [76.9% vs. 45.5%, hazard ratio (HR) = 0.344, P = 0.017]., Conclusions: Early PR training can significantly improve the respiratory function of patients with ARDS after weaning of invasive mechanical ventilation. Continuous active respiratory training after discharge can improve the respiratory function of patients and effectively decrease mortality.

Organochalcogen compounds are prevalent in numerous natural products, pharmaceuticals, agrochemicals, polymers, biological molecules and synthetic intermediates. Direct chalcogenation of C-H bonds has evolved as a step- and atom-economical method for the synthesis of chalcogen-bearing compounds. Nevertheless, direct C-H chalcogenation severely lags behind C-C, C-N and C-O bond formations. Moreover, compared with the C-H monochalcogenation, reports of selective mono-/dichalcogenation and exclusive dichalcogenation of C-H bonds are relatively scarce. The past decade has witnessed significant advancements in selective mono-/dichalcogenation and exclusive dichalcogenation of various C(sp 2 )-H and C(sp 3 )-H bonds via transition-metal-catalyzed/mediated, photocatalytic, electrochemical or metal-free approaches. In light of the significance of both mono- and dichalcogen-containing compounds in various fields of chemical science and the critical issue of chemoselectivity in organic synthesis, the present review systematically summarizes the advances in these research fields, with a special focus on elucidating scopes and mechanistic aspects. Moreover, the synthetic limitations, applications of some of these processes, the current challenges and our own perspectives on these highly active research fields are also discussed. Based on the substrate types and C-H bonds being chalcogenated, the present review is organized into four sections: (1) transition-metal-catalyzed/mediated chelation-assisted selective C-H mono-/dichalcogenation or exclusive dichalcogenation of (hetero)arenes; (2) directing group-free selective C-H mono-/dichalcogenation or exclusive dichalcogenation of electron-rich (hetero)arenes; (3) C(sp 3 )-H dichalcogenation; (4) dichalcogenation of both C(sp 2 )-H and C(sp 3 )-H bonds. We believe the present review will serve as an invaluable resource for future innovations and drug discovery.

While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson's disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW-OR 0.93, 95% CI 0.91-0.96, p = 3.12 × 10 -5 ; MR-Egger-OR 0.93, 95% CI 0.88-0.98, p = 1.45 × 10 -2 ; weighted median-OR 0.93, 95% CI 0.89-0.98, p = 2.76 × 10 -3 ; and weighted mode-OR 0.94, 95% CI 0.9-0.98, p = 1.58 × 10 -2 ). The findings were then replicated with another independent GWAS dataset on T1DM (IVW-OR 0.97, 95% CI 0.95-0.99, p = 3.10 × 10 -3 ; MR-Egger-OR 0.96, 95% CI 0.93-0.99, p = 1.08 × 10 -2 ; weighted median-OR 0.97, 95% CI 0.94-0.99, p = 1.88 × 10 -2 ; weighted mode-OR 0.97, 95% CI 0.94-0.99, p = 1.43 × 10 -2 ). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.

Objective: Apical periodontitis is the most frequently occurring pathological lesion. Fat mass and obesity-associated protein (Fto) is the first identified RNA N6-methyladenosine demethylase. However, whether Fto regulates apical periodontitis remains unclear. This study aimed to explore the mechanisms of Fto in the tumor necrosis factor-α (TNF-α)-induced inflammatory response., Materials and Methods: We established an apical periodontitis model. An immortalized cementoblast cell line (OCCM-30) cells were exposed to TNF-α. Fto, Il6, Mcp1, and Mmp9 expressions were assessed by qRT-PCR. We knocked down Fto using lentiviruses and detected TNF-α-induced inflammation-related gene expressions and mRNA stability., Results: Mice with apical periodontitis showed downregulation of Fto expression. OCCM-30 cells exposed to TNF-α showed an upregulation of inflammation-related genes with a decrease in Fto. Furthermore, knockdown of Fto promoted the expressions of Il6, Mcp1, and Mmp9 in TNF-α-treated OCCM-30 cells as compared with negative control cells, whereas it did not affect the mRNA stability. Interestingly, Fto knockdown activated the p65, p38, and ERK1/2 pathways, and it slightly activated the JNK signaling pathway after TNF-α administration in OCCM-30 cells., Conclusion: A TNF-α-induced decrease in the expression of Fto might play a critical role in the inflammatory response in cementoblasts, and knockdown of Fto might upregulate the inflammatory response., (© 2022 Wiley Periodicals LLC.)

Periodontitis is a prevalent oral disease. It can cause tooth loss and has a significant impact on patients' quality of life. While existing treatments can only slow the progression of periodontitis, they are unable to achieve complete regeneration and functional reconstruction of periodontal tissues. As a result, regenerative therapies based on biomaterials have become a focal point of research in the field of periodontology. Despite numerous studies reporting the superiority of new materials in periodontal regeneration, limited progress has been made in translating these findings into clinical practice. This may be due to the lack of appropriate animal models to simulate the tissue defects caused by human periodontitis. This review aims to provide an overview of established animal models for periodontal regeneration, examine their advantages and limitations, and outline the steps for model construction. The objective is to determine the most relevant animal models for periodontal regeneration based on the hypothesis and expected outcomes.

Information asymmetry is widespread in the P2P online lending market, creating an imbalance in the position of lenders and borrowers. This paper aims to expand the process of information exchange between lenders and borrowers by analyzing the link between soft information such as borrowers' loan descriptions and lending outcomes. Based on the transaction data of the 'Renrendai' platform, this paper analyzed the linguistic features and extracted the content of loan descriptions using a latent Dirichlet allocation (LDA) theme model. To further explore the value of loan descriptions in predicting lending success, this paper conducts a prediction study based on a support vector machine model. It is found that: lenders focus on effective information in the loan descriptions, the linguistic complexity affects the transaction, with simple and direct statements being more favorable; the content for building a good personal image of the borrower will significantly contribute to the lending success. In the prediction study section, it is demonstrated that loan descriptions' language feature indicators can improve prediction accuracy. This paper uncovers the importance of loan descriptions in online lending transactions, which has implications in assisting lenders' investment judgments, as well as in platform information system improvements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sun 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.)

Objectives: Interleukin (IL)-38 was discovered as an anti-inflammatory factor. However, IL-38's role in M1 macrophage polarization in the temporomandibular joint (TMJ) and the related mechanism are still unclear. We aimed to explore the effect and the mechanism of IL-38 on synovial inflammation in the TMJ in this study., Methods: The expression of IL-38 in the TMJ synovium and macrophages was determined using immunohistochemistry (IHC) and Western blotting (WB). M1 macrophage polarization was induced by LPS, the macrophages were pre-treated with IL-38, and the levels of inflammatory markers associated with M1 macrophages were measured. To assess the mechanism of IL-38, small-interfering RNA (siRNA)-GLUT-1 and STF31 were administered to macrophages, and the affected pathways were identified by WB. The effect of macrophage-conditioned medium (CM) on chondrocyte function was also determined. Finally, a mouse model of CFA-induced TMJ inflammation was established. Histological staining and IHC were used to determine the effect of IL-38., Results: IL-38 was detected at high levels in macrophages after lipopolysaccharide (LPS)challenge, and IL-38 downregulated M1 macrophage-related proinflammatory markers (iNOS, IL-6, TNF-α, and COX-2) in vitro. IL-38 suppressed M1 polarization by inhibiting GLUT-1 expression, NF-κB signaling, and MAPK signaling. Intriguingly, CM from macrophages that were pretreated with IL-38 and STF31 decreased inflammatory protein expression in chondrocytes. In addition, intra-articular injection of recombinant IL-38 ameliorated synovial inflammation in the TMJ by inhibiting M1 macrophage polarization and suppressing cartilage inflammation in vivo., Conclusions: IL-38 is a novel anti-inflammatory factor that contributes to alleviating TMJ inflammation by inhibiting macrophage M1 polarization, thereby ameliorating chondrocyte inflammation and restoring TMJ homeostasis., 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 Elsevier B.V. All rights reserved.)

Purpose: SYVN1, a gene involved in endoplasmic reticulum-associated degradation, has been found to exert a protective effect by inhibiting inflammation in retinopathy. This study aimed to clarify whether SYVN1 is involved in the pathogenesis of retinopathy of prematurity (ROP) and its potential as a candidate for target therapy., Methods: Human retinal microvascular endothelial cells (hRMECs) and a mouse model of oxygen-induced retinopathy (OIR) were used to reveal the retinopathy development-associated protein expression and molecular mechanism. An adenovirus overexpressing SYVN1 or vehicle control was injected intravitreally at postnatal day 12 (P12), and the neovascular lesions were evaluated in retinal flatmounts with immunofluorescence staining, and hematoxylin and eosin staining at P17. Visual function was assessed by using electroretinogram (ERG)., Results: Endogenous SYVN1 expression dramatically decreased in hRMECs under hypoxia and in ROP mouse retinas. SYVN1 regulated the signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) axis. SYVN1 overexpression promoted ubiquitination and degradation of STAT3, decreased the levels of phospho-STAT3, secretion of VEGF, and formation of neovascularization in hRMECs, which could be rescued by STAT3 activator treatment. In addition, SYVN1 overexpression prevented neovascularization and extended physiologic retinal vascular development in the retinal tissues of OIR mice without affecting retinal function., Conclusions: SYVN1 has a protective effect against OIR, and the molecular mechanisms are partly through SYVN1-mediated ubiquitination of STAT3 and the subsequent downregulation of VEGF. These findings strongly support our assumption that SYVN1 confers ROP resistance and may be a potentially novel pharmaceutical target against proliferative retinopathy.

In Brief: Normal gene expression during early embryonic development and in the placenta is crucial for a successful pregnancy. Nicotine can disrupt normal gene expression during development, leading to abnormal embryonic and placental development., Abstract: Nicotine is a common indoor air pollutant that is present in cigarette fumes. Due to its lipophilic nature, nicotine can rapidly transport through membrane barriers and spread throughout the body, which can lead to the development of diseases. However, the impact of nicotine exposure during early embryonic development on subsequent development remains elusive. In this study, we found that nicotine significantly elevated reactive oxygen species, DNA damage and cell apoptosis levels with the decrease of blastocyst formation during early embryonic development. More importantly, nicotine exposure during early embryonic development increased placental weight and disrupted placental structure. In molecular level, we also observed that nicotine exposure could specifically cause the hypermethylation of Phlda2 promoter (a maternally expressed imprinted gene associated with placental development) and reduce the mRNA expression of Phlda2. By RNA sequencing analysis, we demonstrated that nicotine exposure affected the gene expression and excessive activation of the Notch signaling pathway thereby affecting placental development. Blocking the Notch signaling pathway by DAPT treatment could recover abnormal placental weight and structure induced by nicotine exposure. Taken together, this study indicates that nicotine causes the declining quality of early embryos and leads to placental abnormalities related to over-activation of the Notch signaling pathway.

Increasing the thickness of a superconducting layer and simultaneously reducing the thickness effect in iron-based superconducting coated conductors are particularly essential for improving the critical current I c . Here, for the first time, we have deposited high-performance FeSe 0.5 Te 0.5 (FST) superconducting films up to 2 μm on LaMnO 3 -buffered metal tapes by pulsed laser deposition. An interface engineering strategy, alternating growth of a 10 nm-thick nonsuperconducting FST seed layer and a 400 nm-thick FST superconducting layer, was employed to guarantee the crystalline quality of the films with thicknesses of the order of micrometers, resulting in a highly biaxial texture with grain boundary misorientation angle less than the critical value θ c ∼ 9°. Moreover, the thickness effect, that the critical current density ( J c ) shows a clear dependence on thickness as in cuprates, is reduced by the interface engineering. Also, the maximum J c was found for a 400 nm-thick film with 1.3 MA/cm 2 in self-field at 4.2 K and 0.71 MA/cm 2 ( H ∥ ab ) and 0.50 MA/cm 2 ( H ∥ c ) at 9 T. Anisotropic Ginzburg-Landau scaling indicates that the major pinning centers vary from correlated to uncorrelated as the film thickness increases, while the thickness effect is most likely related to the weakening of flux pinning by the fluctuation of charge-carrier mean free path (δ l ) and strengthening of flux pinning caused by the variation of superconducting transition temperature (δ T c ) due to off-stoichiometry with thickness.

Introduction: Progressive cerebral venous sinus thrombosis (CVST)-induced visual loss remains problematic, despite decreasing overall mortality owing to early diagnosis and aggressive treatment. Optic nerve sheath fenestration (ONSF) improves or stabilizes visual function in patients with idiopathic intracranial hypertension; however, its role in CVST awaits elucidation. We evaluated the efficacy and safety of ONSF in resolving CVST-induced visual impairment based on long-term observation., Methods: This observational study included 18 patients with progressive CVST-induced visual loss, who had undergone ONSF between 2012 and 2021. Patients received maximum medical therapy, including anticoagulants and intracranial pressure (ICP)-lowering medications. The best-corrected visual acuity (BCVA), visual fields (VFs), and optic nerve head were assessed at baseline, at 1 week after ONSF, and over 6 months after ONSF. Activities of daily living (ADL) and National Eye Institute Visual Function Questionnaire-25 (VFQ-25) scores were assessed at final follow-up., Results: Thirty-one ONSF-treated eyes of 18 patients were included. The mean follow-up duration was 35.6 months (range 1 week-8 years). Two patients were lost to follow-up. Before ONSF, all patients were still experiencing progressive visual loss despite receiving adequate anticoagulation and ICP-lowering therapy. Postoperative BCVA remained stable or improved in 25/31 eyes (80.6%) 1 week postoperatively and 17/28 eyes (60.7%) upon final follow-up. All papilledema resolved postoperatively. No complications were reported except for one transient postoperative diplopia. The median ADL score was 100 (range 25-100), and the mean total VFQ-25 score was 40.6 (range 9.5-87.3)., Conclusion: This was the largest study to describe ONSF's role in CVST based on a long-term follow-up. Considering its efficacy and favorable safety, ONSF can be considered an important adjunctive approach to resolving progressive visual loss of CVST patients, on the basis of anticoagulation and ICP-lowering therapy., (© 2023. The Author(s).)

The electrocatalytic nitrogen reduction reaction (NRR) is a green and sustainable approach for producing ammonia. Low-cost carbon-based materials are promising catalysts for the electrochemical NRR. Among them, Cu-N 4 -graphene is a unique catalytic substrate. Its catalytic performance for the NRR has remained unclear as N 2 can only be physisorbed on such a substrate. In this work, we focus on the influence of an electronic environment on the electrocatalytic NRR. DFT computations reveal that the NN bond can be effectively activated at a surface charge density of -1.88 × 10 14 e cm -2 on Cu-N 4 -graphene and further the NRR proceeds via an alternating hydrogenation pathway. This work offers a new insight into the mechanism of the electrocatalytic NRR and emphasizes the importance of environmental charges in the electrocatalytic process of the NRR.

Despite the remarkable clinical responses achieved with immune checkpoint blockade therapy, the response rate is relatively low and only a subset of patients can benefit from the treatment. Aberrant RNA accumulation can mediate IFN signaling and stimulate an immune response, suggesting that targeting RNA decay machinery might sensitize tumor cells to immunotherapy. With this in mind, we identified an RNA exoribonuclease, XRN1, as a potential therapeutic target to suppress RNA decay and stimulate antitumor immunity. Silencing of XRN1 suppressed tumor growth in syngeneic immunocompetent mice and potentiated immunotherapy efficacy, while silencing of XRN1 alone did not affect tumor growth in immunodeficient mice. Mechanistically, XRN1 depletion activated IFN signaling and the viral defense pathway; both pathways play determinant roles in regulating immune evasion. Aberrant RNA-sensing signaling proteins (RIG-I/MAVS) mediated the expression of IFN genes, as depletion of each of them blunted the elevation of antiviral/IFN signaling in XRN1-silenced cells. Analysis of pan-cancer CRISPR-screening data indicated that IFN signaling triggered by XRN1 silencing is a common phenomenon, suggesting that the effect of XRN1 silencing may be extended to multiple types of cancers. Overall, XRN1 depletion triggers aberrant RNA-mediated IFN signaling, highlighting the importance of the aberrant RNA-sensing pathway in regulating immune responses. These findings provide the molecular rationale for developing XRN1 inhibitors and exploring their potential clinical application in combination with cancer immunotherapy., Significance: Targeting XRN1 activates an intracellular innate immune response mediated by RNA-sensing signaling and potentiates cancer immunotherapy efficacy, suggesting inhibition of RNA decay machinery as a novel strategy for cancer treatment., (©2023 American Association for Cancer Research.)

To study the anti-tumor effect of Cistanche deserticola Y. Ma , HepG2 cells were treated with 0, 3.5, 10.5, 21, 31.5, and 42 μg/ml of total glycosides (TG) from Cistanche deserticola . The HepG2 cell survival rate and 50% inhibition concentration (IC 50 ) were detected using the CCK-8 method, and the level of reactive oxygen species (ROS) was detected by using a DCFH-DA fluorescence probe. Finally, a Seahorse XFe24 energy analyzer (Agilent, United States) was used to detect cell mitochondrial pressure and glycolytic pressure. The results showed that TG could reduce the survival rate of HepG2 cells and that the IC 50 level was 35.28 μg/ml. With increasing TG concentration, the level of ROS showed a concentration-dependent upward trend. Energy metabolism showed that each dose group of TG could significantly decline the mitochondrial respiratory and glycolytic functions of HepG2 cells. In conclusion, TG could significantly inhibit the mitochondrial respiration and glycolysis functions of HepG2 cells, increase the level of ROS, and inhibit cell proliferation. Thus, this experiment pointed out that Cistanche deserticola can be used as a source of anti-cancer foods or drugs in the future. However, further studies on its mechanisms and clinical applications are needed., Competing Interests: Y-jJ was employed by Inner Mongolia Sankou Biotechnology Co., Ltd. The remaining 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 Feng, Zhou, Zhou, Jiang, Sun, Song, Cui, Yan and Wang.)

Elastin is considered an excellent resource for obtaining antioxidant peptides due to unique amino acid composition. However, it is hardly soluble in water or in dilute acid or alkali; most of the elastases have low yields for preparing elastin peptides, making it difficult to meet industrial applications. To address above problems, enzymes capable of hydrolyzing elastin into soluble peptides were preferred from typical commercial protease preparations. The optimal enzymatic hydrolysis process conditions for elastin peptides were obtained by response surface optimization design. The molecular weight, amino acid composition, and antioxidant activity of the enzymatic hydrolysis products were determined. The results show that the alkaline protease NUE has a strong hydrolysis effect. The optimized enzymatic hydrolysis conditions are as follows: substrate concentration is 5%, enzyme concentration is 650 U/mL, pH is 10.0, temperature is 60 °C, time is 6 h. The degree of hydrolysis of elastic protein peptides obtained through this method is 14.42%. The distribution of molecular weight is 200-6500 Da, more than 85% of the component molecular amount is greater than 800 Da; the amino acid content related to antioxidant activity has reached 68 mg/100 mg, so it has extremely high free radical clearance. Compared with acid and alkali methods, the anti-oxidation capacity of enzyme-based peptide is better, the reaction conditions are milder, the yield is higher, and by-products and pollutants are fewer. It provides an effective way to industrialized production of elastin peptides with high antioxidant activity and a basis for its widespread application in the food and pharmaceutical industries., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Current staging criteria for papillary thyroid cancer (PTC) do not include the number of metastatic lymph nodes (LNs), which is highly predictive of survival in multiple cancers. The LN metastasis burden is particularly relevant for older adults with thyroid cancer because of their poor prognosis. We examined a modified staging system for this population utilizing node number (Nn)., Methods: Overall, 14,341 patients aged 55 years or older with stage I-IVB PTC were identified in the 2004-2015 Surveillance, Epidemiology and End Results database. Cox regression models were conducted to test the relationship between positive LN number and PTC-specific survival (PTCSS). Independent training/validation sets were used to derive and validate a new revised TNnM grouping. The 8th edition American Joint Committee on Cancer TNM staging system was compared with TNnM stage by calculating the 10-year PTCSS rates, Harrell's concordance index (C-index), and Akaike's information criterion (AIC)., Results: An increase in number of LN metastases was identified as an independent, negative prognostic factor for PTCSS in multivariate analysis. 10-year PTCSS for stage I-IVB based on the AJCC 8th edition TNM were 98.83%, 93.49%, 71.21%, 72.95%, and 58.52%, respectively, while 10-year PTCSS for the corresponding stage in the TNnM were 98.59%, 92.2%, 83.26%, 75.24%, and 56.73%, respectively. The revised TNnM stage was superior, with a higher C-index and a lower AIC in both the training and validation cohorts., Conclusion: The TNnM staging system for PTC patients ≥ 55 years could be associated with improved outcomes. External validation studies of this system are warranted., 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 Sun, Chen, Sun, Tian and He.)

N 6 -methyladenosine (m 6 A) is the most prevalent mRNA modification which plays crucial roles in various biological processes, but its role in cementogenesis remains largely unknown. Here, using time-series transcriptomic analysis, we reveal that mRNA m 6 A demethylase Fat mass and obesity-associated protein (FTO) is involved in cementogenesis. Knocking down FTO decreases cementoblast differentiation and mineralization in both OCCM-30 cellular model and murine ectopic bone formation model. Mechanistically, we find that FTO directly binds Runt-related transcription factor 2 (Runx2) mRNA, an important cementogenesis factor, thus protecting it from YTH domain-containing family protein 2 (YTHDF2) mediated degradation, when cementoblasts are differentiating. Knocking down YTHDF2 restores the expression of Runx2 in FTO-knockdown cells. Moreover, under inflammatory conditions, TNF-α inhibits cementoblast differentiation and mineralization partly through FTO/RUNX2 axis. Collectively, our study reveals an important regulatory role of FTO/RUNX2 axis in normal and pathological cementogenesis., 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. Published by Elsevier B.V.)

Objectives: Where patient-reported outcome measures (PROMs) may be administered at multiple patient visits, it is advantageous to capture these symptoms with as few questions as possible. In this study, the M.D. Anderson Head and Neck Symptom Inventory (MDASI-HN), and the M.D. Anderson Dysphagia Inventory (MDADI) is compared to determine if using the MDASI-HN alone would overlook symptoms identified with MDADI., Methods: The MDASI-HN and the MDADI were completed by 156 patients, postradiotherapy for head and neck cancer (HNC). Associations between the two instruments were analyzed using correlation analysis, unsupervised machine learning, and sensitivity analysis., Results: Little correlation was found between the two surveys; however, there was overlap between MDASI-HN dry mouth and many MDADI items, confirming that dry mouth is an important factor in difficulty swallowing, and patient QoL. Taking longer to eat (MDADI), was the most commonly reported item overall, with 85 (54%) patients rating it as moderate-severe. Dry mouth was the most endorsed MDASI-HN item (68, 44%). There were 51 patients missed by the MDASI-HN, reporting no moderate-severe symptoms, but reported one or more moderate-severe QoL impacts on MDADI. If patients who reported a score of 2 or higher on the MDASI-HN Dry Mouth item are flagged as requiring follow-up, the number of patients missed by MDASI-HN drops to 15., Conclusion: In an HNC clinic where MDASI-HN is routinely administered, assessment of symptoms and QoL might be enhanced by reducing the value at which MDASI Dry Mouth is considered moderate-severe to 2., Level of Evidence: 3 Laryngoscope, 132:2388-2395, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To show the clinical characteristics, identify the magnetic resonance imaging (MRI) and optical coherence tomography (OCT) features, and observe the visual outcome of methanol-induced optic neuropathy., Methods: Clinical data were retrospectively collected from in-patients diagnosed with methanol-induced optic neuropathy in the Neuro-Ophthalmology Department of the Chinese People's Liberation Army General Hospital from January 2016 to January 2021., Results: Eight patients were included in this study. The exposure time was 6-34 h for ingestion, 3-4 months for inhalation, and more than ten years for skin absorption. All patients demonstrated bilateral acute visual impairment. Seven of eight patients had other accompanying systemic symptoms. Seven of eight patients demonstrated optic nerve lesions in MRI, and five presented with a hyperintense T2 signal in a "central" type. OCT showed the macular ganglion cell layer and inner plexiform layer (mGCL-IPL) thinning before the peripapillary retinal nerve fiber layer (pRNFL) thinning. The visual improvement was achieved transiently for seven of eight patients after treatment. One patient with a mitochondrial DNA mutation maintained a bilateral no-light perception (NLP) from the onset to the last visit. All patients had poor visual prognoses, with either light perception or NLP., Conclusions: Methanol-induced optic neuropathy is a rare bilateral optic neuropathy with a poor visual outcome. A centrally hyperintense T2 signal of the optic nerve is common in methanol-induced optic neuropathy. The thinning of the mGCL-IPL is more sensitive than that of the pRNFL for early diagnosis. A mitochondrial genetic defect may be a predisposing factor for methanol-induced optic neuropathy., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Qiao Sun et al.)

Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases., Materials and Methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018., Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time., Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile., 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 Sun, Zhou, Sun, Li, Liu, Song, Yang, Teng, Wei and Xu.)

Transforming glyoxal to value-added glyoxylic acid (GA) is highly desirable but challenging due to the uncontrollable over-oxidation. In this work, we report on a first demonstration of semi-oxidation of glyoxal with high selectivity (86.5%) and activity on WO 3 nanoplate photoanode through the photoelectrochemical strategy. The optimization of reactivity was achieved via crystal facet regulation, showing a satisfactory GA production rate of 308.4 mmol m -2 h -2 , 84.0% faradaic efficiency, and 4.3% total solar-to-glyoxylic acid efficiency on WO 3 with enriched {200} facets at 1.6 V versus RHE. WO 3 with a high {200} facet ratio exhibits more efficient electron-hole transfer kinetics, resulting in the facilitated formation of hydroxyl radicals ( • OH) and glyoxal radicals. Meanwhile, the theoretical calculation results indicate that the high selectivity and activity come from the strong adsorption ability for glyoxal and the low reaction energy for glyoxal radical generation on the (200) facets of WO 3 . Moreover, the high energy demand toward oxalic acid production on WO 3 leads to the exciting semi-oxidation process.

Chemo-/radioresistance is the most important reason for the failure of glioblastoma (GBM) treatment. Reversing the chemo-/radioresistance of GBM for boosting therapeutic efficacy is very challenging. Herein, we report a significant decrease in the chemo-/radioresistance of GBM by the in situ generation of SO 2 within a tumor, which was released on demand from the prodrug 5-amino-1,3-dihydrobenzo[ c ]thiophene 2,2-dioxide (ATD) loaded on rare-earth-based scintillator nanoparticles ( i.e. , NaYF 4 :Ce@NaLuF 4 :Nd@ATD@DSPE-PEG 5000 , ScNPs) under X-ray irradiation. Our novel X-ray-responsive ScNPs efficiently converted highly penetrating X-rays into ultraviolet rays for controlling the decomposition of ATD to generate SO 2 , which effectively damaged the mitochondria of temozolomide-resistant U87 cells to lower the production of ATP and inhibit P-glycoprotein (P-gp) expression to reduce drug efflux. Meanwhile, the O 6 -methylguanine-DNA methyltransferase (MGMT) of drug-resistant tumor cells was also reduced to prevent the repair of damaged DNA and enhance cell apoptosis and the efficacy of chemo-/radiotherapy. The tumor growth was obviously suppressed, and the mice survived significantly longer than untreated temozolomide-resistant GBM-bearing mice. Our work demonstrates the potential of SO 2 in reducing chemo-/radioresistance to improve the therapeutic effect against resistant tumors if it can be well controlled and in situ generated in tumor cells. It also provides insights into the rational design of stimuli-responsive drug delivery systems for the controlled release of drugs.

A bandpass filter integrated metalens based on electromagnetically induced transparency (EIT) for long-wavelength infrared (LWIR) imaging is designed in this paper. The bandwidth of the metalens, which is a diffractive optical element, decreases significantly with the increase of the aperture size to a fixed f-number, which leads to the decline of imaging performance. The same material composition and preparation process of the metalens and the EIT metasurface in the long-wavelength infrared make it feasible that the abilities of focusing imaging and filtering are integrated into a metasurface device. With the purpose of validating the feasibility of this design method, we have designed a 300-μm-diameter integrated metalens whose f-number is 0.8 and the simulation was carried out. The introduction of EIT metasurface does not affect the focusing near the diffraction limit at the target wavelength, and greatly reduces the influence of stray light caused by non-target wavelength incident light. This bandpass filter integrated metalens design method may have a great potential in the field of LWIR compact optical systems.

Developing dynamic and highly sensitive methods for imaging M2-type tumor-associated macrophages (TAMs) is vital for monitoring the tumor progression and assessing the therapeutic efficacy. Here, the fabrication and application of rationally designed Er-based rare-earth nanoprobes for the targeted imaging of M2-type TAMs in glioblastoma (GBM) through the second near-infrared (NIR-II) fluorescence beyond 1500 nm is reported. The NIR-IIb fluorescence of Er-based rare-earth nanoparticles can be remarkably enhanced by optimizing their core-shell structures and the shell thickness, which allows for in vivo imaging under excitation by a 980 nm laser with the lowest power density (40 mW cm -2 ). These bright Er-based nanoparticles functionalized with M2pep polypeptide show notable targeting ability to M2-type macrophages, which has been well tested in both in vitro and in vivo experiments by their up-conversion (UC) fluorescence (540 nm) and down-shifting (DS) fluorescence (1525 nm), respectively. The targeting capability of these nanoprobes in vivo is also demonstrated by the overlap of immunofluorescence of M2-type TAMs and Arsenazo III staining of rare-earth ions in tumor tissue. It is envisioned that these nanoprobes can serve as a companion diagnostic tool to dynamically assess the progression and prognosis of GBM., (© 2022 Wiley-VCH GmbH.)

Lymphoma is a serious malignant tumor that contains more than 70 different types and seriously endangers the body's lymphatic system. The lymphatic system is the regulatory center of the immune system and is important in the immune response to foreign antigens and tumors. Studies showed that multiple genetic variants are associated with lymphoma but determining the pathogenic mechanisms remains a challenge. In the present study, we first applied the Gene Ontology (GO) and KEGG pathway enrichment analyses of lymphoma-associated and lymphoma-nonassociated genes. Next, the Boruta and max-relevance and min-redundancy feature selection methods were performed to filter and rank features. Then, features preselected and ranked using the incremental feature selection method were applied for the decision tree model to identify the best GO terms and KEGG pathways and extract classification rules. Results indicate that our predicted features, such as B-cell activation, negative regulation of protein processing, negative regulation of mast cell cytokine production, and natural killer cell-mediated cytotoxicity, are associated with the biological process of lymphoma, consistent with those of recent publications. This study provides a new perspective for future research on the molecular mechanisms of lymphoma., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Qiao Sun et al.)

An all-silicon long-wavelength infrared (LWIR) achromatic metalens based on deep silicon etching is designed in this paper. With a fixed aperture size, the value range of the equivalent optical thickness of the non-dispersive meta-atoms constructing the achromatic metalens determines the minimum f-number. The fabrication characteristic with high aspect ratio of deep silicon etching amplifies the difference value of optical thickness between different meta-atoms by increasing the propagation distance of the propagation mode, which ensures a small f-number to obtain a better imaging resolution. A 280-µm-diameter silicon achromatic metalens with a f-number of 1 and the average focusing efficiency of 27.66% has been designed and simulated to validate the feasibility of this strategy. The simulation results show that the maximum focal length deviation percentage from the target value between the wavelength of 8.6 and 11.4 µm is 1.61%. This achromatic metalens design is expected to play a role in the field of LWIR integrated optical system.

It is significant to evaluate the air quality scientifically for the management of air pollution. As an air quality comprehensive evaluation problem, its uncertainty can be effectively addressed by the Dempster-Shafer (D-S) evidence theory. However, there is not enough research on air quality comprehensive assessment using D-S theory. Aiming at the counterintuitive fusion results of the D-S combination rule in the field of comprehensive decision, an improved evidence theory with evidence weight and evidence decision credibility (here namely DCre-Weight method) is proposed, and it is used to comprehensively evaluate air quality. First, this method determines the weights of evidence by the entropy weight method and introduces the decision credibility by calculating the dispersion of different evidence decisions. An algorithm case shows that the credibility of fusion results is improved and the uncertainty is well expressed. It can make reasonable fusion results and solve the problems of D-S. Then, the air quality evaluation model based on improved evidence theory (here namely the DCreWeight model) is proposed. Finally, according to the hourly air pollution data in Xi'an from June 1, 2014, to May 1, 2016, comparisons are made with the D-S, other improved methods of evidence theory, and a recent fuzzy synthetic evaluation method to validate the effectiveness of the model. Under the national AQCI standard, the MAE and RMSE of the DCreWeight model are 1.02 and 1.17. Under the national AQI standard, the DCreWeight model has the minimal MAE, RMSE, and maximal index of agreement, which validated the superiority of the DCreWeight model. Therefore, the DCreWeight model can comprehensively evaluate air quality. It can provide a scientific basis for relevant departments to prevent and control air pollution., (© 2022. The Author(s).)

KDM6A, an X chromosome-linked histone lysine demethylase, was reported to be frequently mutated in many tumor types including breast and bladder cancer. However, the functional role of KDM6A is not fully understood. Using MCF10A as a model of non-tumorigenic epithelial breast cells, we found that silencing KDM6A promoted cell migration and transformation demonstrated by the formation of tumor-like acini in three-dimensional culture. KDM6A loss reduced the sensitivity of MCF10A cells to therapeutic agents commonly used to treat patients with triple-negative breast cancer and also induced TGFβ extracellular secretion leading to suppressed expression of cytotoxic genes in normal human CD8+ T cells in vitro. Interestingly, when cells were treated with TGFβ, de novo synthesis of KDM6A protein was suppressed while TGFB1 transcription was enhanced, indicating a TGFβ/KDM6A-negative regulatory axis. Furthermore, both KDM6A deficiency and TGFβ treatment promoted disorganized acinar structures in three-dimensional culture, as well as transcriptional profiles associated with epithelial-to-mesenchymal transition and metastasis, suggesting KDM6A depletion and TGFβ drive tumor progression., Implications: Our study provides the preclinical rationale for evaluating KDM6A and TGFβ in breast tumor samples as predictors for response to chemo and immunotherapy, informing personalized therapy based on these findings., (©2022 American Association for Cancer Research.)

The investigation of the interaction between metal ions and DNA has always attracted much attention in the fields of bioinorganic chemistry, supramolecular coordination chemistry, and DNA nanotechnology. Its mode of action can be simply divided into two aspects. On the one hand, it is non-specific electrostatic adsorption, mainly including Na + , K + , Mg 2+ , Ca 2+ and other physiologically regulating ions; on the other hand, it is specific covalent binding, such as Pt 2+ , Hg 2+ , Ag + and other heavy metal ions. This article focuses on the mechanism of action between Ag + and DNA mismatch pair C-C, and summarizes its main characterization methods and various applications. It aims to provide a certain reference for the field of biological devices. With the development of cryo-electron microscopy and liquidcell TEM, the structure of C-Ag + -C is expected to be further characterized, which will be more widely used., (© 2022. The Author(s).)

Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in tumor immunotherapy. As a class of professional phagocytes and antigen-presenting cells in the innate immune system, macrophages can not only directly engulf and clear tumor cells, but also play roles in presenting tumor-specific antigen to initiate adaptive immunity. However, the tumor-associated macrophages (TAMs) usually display tumor-supportive M2 phenotype rather than anti-tumor M1 phenotype. They can support tumor cells to escape immunological surveillance, aggravate tumor progression, and impede tumor-specific T cell immunity. Although many TAMs-modulating agents have shown great success in therapy of multiple tumors, they face enormous challenges including poor tumor accumulation and off-target side effects. An alternative solution is the use of advanced nanostructures, which not only can deliver TAMs-modulating agents to augment therapeutic efficacy, but also can directly serve as modulators of TAMs. Another important strategy is the exploitation of macrophages and macrophage-derived components as tumor-targeting delivery vehicles. Herein, we summarize the recent advances in targeting and engineering macrophages for tumor immunotherapy, including (1) direct and indirect effects of macrophages on the augmentation of immunotherapy and (2) strategies for engineering macrophage-based drug carriers. The existing perspectives and challenges of macrophage-based tumor immunotherapies are also highlighted., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)

Designing high-performance materials for CO 2 capture and conversion is of great significance to reduce the greenhouse effect and alleviate the energy crisis. The strategy of doping is widely used to improve activity and selectivity of the materials. However, it is unclear how the doping densities influence the materials' properties. Herein, we investigated the mechanism of CO 2 capture, separation and conversion on MoS 2 , MoSe 2 and Janus MoSSe monolayers with different boron doping levels using density functional theory (DFT) simulations. The results indicate that CO 2 , H 2 and CH 4 bind weakly to the monolayers without and with single-atom boron doping, rendering these materials unsuitable for CO 2 capture from gas mixtures. In contrast, CO 2 binds strongly to monolayers doped with diatomic boron, whereas H 2 and CH 4 can only form weak interactions with these surfaces. Thus, the monolayers doped with diatomic boron can efficiently capture and separate CO 2 from such gas mixtures. The electronic structure analysis demonstrates that monolayers doped with diatomic doped are more prone to donating electrons to CO 2 than those with single-atom boron doped, leading to activation of CO 2 . The results further indicate that CO 2 can be converted to CH 4 on diatomic boron doped catalysts, and MoSSe is the most efficient of the surfaces studied for CO 2 capture, separation and conversion. In summary, the study provides evidence for the doping density is vital to design materials with particular functions., (© 2021 Wiley-VCH GmbH.)

Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs., (© 2021. The Author(s).)