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Electrocatalytic oxygen reduction reaction via 2e- pathway is a safe and friendly route for hydrogen peroxide (H2O2) synthesis. In order to achieve efficient synthesis of H2O2, it is essential to accurately control the active sites. Here, fragmented polymetric carbon nitride with rich defects (DCN) is designed for H2O2 electrosynthesis. The multi-type defects, including the sodium atom doping in six-fold cavities, the boron atom doping at N-B-N sites and the cyano groups, are successfully created. Owing to the synergistic effect of these defects, the fragmented DCN achieves a high H2O2 yield of 2.28 mol gcat.-1 h-1 and a high Faradic efficiency of nearly 90% in alkaline media at 0.4 V vs. RHE in H-type cell. In neutral media, the H2O2 concentration produced by DCN can reach 1815 mM within 6 h at a potential of 0.2 V vs. RHE, and the H2O2 production rate of DCN is 0.23 mol gcat.-1 h-1. In addition, DCN shows excellent long-term durability in alkaline and neutral media. This study provides a new approach for the design and development of the boron, nitrogen doped carbon-based electrocatalysts for H2O2 electrochemical synthesis., (© 2024 Wiley‐VCH GmbH.)

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

High-entropy oxides are a new type of material with significant application potential. However, the lack of a universal HEO preparation method severely limits the property study and application of HEOs. Herein, we report a universal approach of spray pyrolysis for the preparation of various HEOs and study the electrocatalytic performance of HEOs toward the oxygen evolution reaction. FeCoNiMoWO x HEO exhibits an overpotential of 281 mV at 10 mA cm -2 and a Tafel slope of 34.5 mV dec -1 , which are far superior to those of the corresponding medium-entropy oxide and low-entropy oxide. It is found that the high entropy of the HEO greatly strengthens the interaction between Fe and Mo/W and produces abundant oxygen vacancies (OVs) around Mo and W. This work not only provides a universal preparation method for HEOs but also deepens our understanding of OER catalytic activity of HEOs.

Background and Aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure., Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab)., Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005)., Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure., Competing Interests: Author JZ was employed by company Gobroad Medical Group. Author QZ was employed by company GoBroad Healthcare Group. 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 © 2024 Xue, Zheng, Yang, Liu, Feng, Guo, Shi, Ma, Deng, Xu, Zhang, Zhou, Ke and Hu.)

Here, we report the complete genome sequences of three Porphyromonas gingivalis , one from patient with esophageal cancer (LyEC01), and the other two from periodontally healthy individuals (LyG-1 and LyG-2) in 2021 and 2023. The genome sizes of LyEC01, LyG-1, and LyG-2 were 2,408,275, 2,411,440, and 2,411,481 bp, respectively., Competing Interests: The authors declare no conflict of interest.

Background: Atrial fibrillation is one of the most common cardiac arrhythmias. Myocardial fibrosis is closely associated with atrial remodeling, which leads to heightened risk of atrial fibrillation. This study aimed to explore whether forkhead box protein O3 (FOXO3a) impacts myocardial fibrosis incidence by regulating mitophagy., Methods: Cell viability was assessed by cell counting kit-8 (CCK-8) assays. The expression of vimentin and cytochrome C was detected by immunofluorescence assays. Quantitative real-time polymerase chain reaction (PCR) was used to analyze the relative mRNA level of FOXO3a. Expression of FOXO3a, phosphorylated FOXO3a, Collagen I, Collagen III, alpha-smooth muscle actin (α-SMA), matrix metalloprotease 9 (MMP9), light chain 3 (LC3), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), Parkin, and sequestosome-1 (p62) proteins were determined by western blotting. 5-ethynyl-2'-deoxyuridine (EDU) incorporation was employed to measure cell proliferation. Changes in mitochondrial membrane potential were determined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining. A wound healing assay was used to examine cell migration, and the levels of reactive oxygen species were determined by flow cytometry., Results: The expression of FOXO3a was upregulated in cardiac fibroblasts treated with angiotensin II (AngII), while the expression of phosphorylated FOXO3a was downregulated under these conditions. FOXO3a knockdown significantly inhibited the proliferation, migration and collagen secretion of cardiac fibroblasts treated with AngII. The ratio of LC3 II/I as well as expression of PINK1 and Parkin was increased, and the expression of p62 was decreased, in cardiac fibroblasts treated with AngII. Moreover, these effects were limited by FOXO3a knockdown. Finally, the mitophagy inducer everolimus (RAD001) attenuated the suppressive effect of FOXO3a knockdown on cardiac fibroblast activation., Conclusions: FOXO3a promotes the progress of myocardial fibrosis by triggering mitophagy in cardiac fibroblasts., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

In recent decades, China's rapid urbanization has produced numerous economic benefits while simultaneously creating substantial risks to ecological security. China's 14th Five-Year Plan and the United Nations Sustainable Development Goals (SDGs) have recently explicitly called for the coordinated development of ecological security and urbanization. Given this context, it is important to explore the mechanism by which ecological security and urbanization are coupled and coordinated to promote sustainable development. In this study, an index of the relationship between ecological security and urbanization was established via high-resolution data, and a "Computation-Verification-Coupling" (CVC) framework was constructed. The accuracy of the ecological security index was verified using a linear regression model, and the coordination level between ecological security and urbanization was analyzed via a coupled coordination model (CCM). The results revealed a steady increase in the ecological security index from 2010 to 2020; the proportion of the area above the medium level increased from 63.1 % to 74.1 %. The urbanization index in core counties exhibited rapid growth, with level V urbanized areas expanding from 5.5 % to 9.9 %. The ecological security verification model produced a coefficient of determination (R²) of 0.75685, indicating a satisfactory degree of predictive capability. From 2010-2020, the coupled coordination improved, with the high coordination area accounting for 48.8 % and the extreme discoordination area decreasing from 1.8 % to 1.0 %. Coordinated development exhibited a stable progression, characterized by a cyclical evolution from initial coupling to antagonistic coupling and finally to coordinated development. This framework can be used not only to investigate the relationship between ecological security and urbanization but also to provide a quantifiable measure of progress toward achieving the SDGs., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Metallic-phase MoS 2 exhibits Pt-comparable electrocatalytic hydrogen evolution reaction (HER) performance in acidic conditions. However, the controllable synthesis of metallic-phase MoS 2 is quite challenging because the key factor determining the phase types of MoS 2 during synthesis is still unclear. Herein, the effect of organic sulfur sources on the formed MoS 2 phase is studied by use of thioacetamide (TAA), l-cysteine, and thiourea as sulfur sources. The TAA and l-cysteine produce metallic MoS 2 , while thiourea gives rise to semiconducting MoS 2 . Owing to the metallic phase and smaller size, the MoS 2 prepared with TAA and l-cysteine has a higher electrocatalytic HER activity than the MoS 2 obtained from thiourea. The HER overpotential of MoS 2 synthesized with TAA is only 210 mV for reaching the current density of 10 mA/cm 2 , and the corresponding Tafel slope is 44 mV/decade. Further studies find that the decomposition temperature of sulfur precursors is the key factor for the formation of metallic MoS 2 . Sulfur precursors with a lower decomposition temperature release sulfur ions quickly, which in turn stabilize the metallic phase and inhibit the growth of MoS 2 into large sizes. Our findings unveil the key factor for controlling the phase type of MoS 2 synthesized from organic sulfur precursors and will be very helpful for the synthesis of MoS 2 with high electrocatalytic activity.

The sluggish four-electron processes of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) limit the development of rechargeable Zn-air batteries (RZABs). Highly efficient ORR/OER bifunctional electrocatalysts are therefore highly desired for the commercialization of RZABs in large scale. Herein, the Fe-N 4 -C (ORR active sites) and NiFe-LDH clusters (OER active sites) are successfully integrated within a NiFe-LDH/Fe,N-CB electrocatalyst. The NiFe-LDH/Fe,N-CB electrocatalyst is first prepared by the introduction of Fe-N 4 into carbon black (CB), followed by the growth of NiFe-LDH clusters. The cluster nature of NiFe-LDH effectively avoids the blocking of Fe-N 4 -C ORR active centers and affords excellent OER activity. The NiFe-LDH/Fe,N-CB electrocatalyst thus exhibits an excellent bifunctional ORR and OER performance, with a potential gap of only 0.71 V. The NiFe-LDH/Fe,N-CB-based RZAB exhibits an open-circuit voltage of 1.565 V and a specific capacity of 731 mAh g Zn -1 . Particularly, the NiFe-LDH/Fe,N-CB-based RZAB displays excellent long-term charging/discharging cyclic stability and rechargeability. Even at a large charging/discharging current density (20 mA cm 2 . Particularly, the NiFe-LDH/Fe,N-CB-based RZAB displays excellent long-term charging/discharging cyclic stability and rechargeability. Even at a large charging/discharging current density (20 mA cm -2 ), the charging/discharging voltage gap is only ∼1.33 V and exhibits an increase smaller than 5% after 140 cycles. This work provides a new low-cost bifunctional ORR/OER electrocatalyst with high activity and superior long-term stability and will be helpful to the commercialization of RZAB in large scale.

Ecological vulnerability is the main index to evaluate areal environmental stability and monitor the development of ecological environment. Longdong area is a typical Loess Plateau area with complex terrain, serious soil erosion, mineral resource development, and other human activities leading to the ecological vulnerability evolution of the area, but the monitoring of its ecological status and the determination of its factors are still lacking. Based on the ecological characteristics of Longdong area, this study constructed an ecological vulnerability system including natural, social, and economic data and used the fuzzy analytic hierarchy process (FAHP) to study the temporal and spatial evolution of ecological vulnerability from 2006 to 2018. A model for quantitative analysis of the evolution of ecological vulnerability and correlation of influencing factors was ultimately developed. The results showed that (1) from 2006 to 2018, the ecological vulnerability index (EVI) had a minimum value of 0.232 and a maximum value of 0.695. EVI was high in the northeast and southwest of Longdong area and low in the central region. (2) At the same time, the areas of potential vulnerability and mild vulnerability increased, and the areas of slight vulnerability, moderate vulnerability, and severe vulnerability decreased. (3) The correlation coefficient between average annual temperature and EVI exceeded 0.5 in four years, and the correlation coefficient between population density and per capita arable land area and EVI exceeded 0.5 in two years showed significant correlation. The results reflect the spatial pattern and influencing factors of ecological vulnerability in typical arid areas of northern China. Additionally, it served as a resource for researching the interrelationships of the variables affecting ecological vulnerability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Titanium-tantalum (Ti-Ta) alloy has excellent biomechanical properties with high strength and low Young's modulus, showing great application potential in the biomedical industry. In this study, Ti-Ta alloy samples were prepared by laser powder bed fusion (LPBF) technology with mixed pure 75 wt.% Ti and 25 wt.% Ta powders as the feedstock. The maximum relative density of Ti-Ta samples prepared by LPBF reached 99.9%. It is well-accepted that four nonequilibrium phases, namely, α', α″ and metastable β phase exist in Ti-Ta alloys. The structure of α', α″ and β are hexagonal close-packed (HCP), base-centered orthorhombic (BCO) and body-centered cubic (BCC), respectively. X-ray Diffraction (XRD) analysis showed that the α' phase transformed to the α″ phase with the increase of energy density. The lamellar α'/α″ phases and the α″ twins were generated in the prior β phase. The microstructure and mechanical properties of the Ti-Ta alloy were optimized with different LPBF processing parameters. The samples prepared by LPBF energy density of 381 J/mm 3 had a favorable ultimate strength (UTS) of 1076 ± 2 MPa and yield strength of 795 ± 16 MPa. The samples prepared by LPBF energy density of 76 had excellent ductility, with an elongation of 31% at fracture.

Multipartite Einstein-Podolsky-Rosen (EPR) steering is a key resource in a quantum network. Although EPR steering between spatially separated regions of ultracold atomic systems has been observed, deterministic manipulation of steering between distant quantum network nodes is required for a secure quantum communication network. Here, we propose a feasible scheme to deterministically generate, store, and manipulate one-way EPR steering between distant atomic cells by a cavity-enhanced quantum memory approach. While optical cavities effectively suppress the unavoidable noises in electromagnetically induced transparency, three atomic cells are in a strong Greenberger-Horne-Zeilinger state by faithfully storing three spatially separated entangled optical modes. In this way, the strong quantum correlation of atomic cells guarantees one-to-two node EPR steering is achieved, and can perserve the stored EPR steering in these quantum nodes. Furthermore, the steerability can be actively manipulated by the temperature of the atomic cell. This scheme provides the direct reference for experimental implementation for one-way multipartite steerable states, which enables an asymmetric quantum network protocol.

Little is known about the presence and possible role of Porphyromonas gingivalis ( P. gingivalis ) in nasopharyngeal carcinoma (NPC), its co-infection with Epstein-Barr virus (EBV), or their association with clinical characteristics of patients with NPC in Central China, where NPC is non-endemic. A total of 45 NPC formalin-fixed paraffin-embedded (FFPE) tissues were retrospectively analyzed using immunohistochemistry (IHC) and a nested PCR combined with DNA sequencing to detect the presence of P. gingivalis , and using reverse transcription-quantitative PCR to detect the presence of EBV. Clinical data including EBV and P. gingivalis status were associated with overall survival (OS). All tumors were undifferentiated, non-keratinizing carcinomas, of which 40/45 (88.9%) were positive for EBV (EBV + ), 26/45 (57.8%) were positive for P. gingivalis (by IHC), and 7/45 (15.6%) were positive for P. gingivalis DNA ( P. gingivalis + ). All seven P. gingivalis DNA-positive NPCs were co-infected with EBV. The 5-year survival rates of the patients with EBV - / P. gingivalis - , EBV + / P. gingivalis - , and EBV + / P. gingivalis + tumors were 60.0% (3/5), 39.4% (13/33) and 42.9% (3/7), respectively. No significant difference was found between the OS of NPC patients among the different infection groups (P=0.793). In conclusion, to the best of our knowledge, this is the first study to describe and confirm the presence of P. gingivalis in FFPE tissues from patients with NPC. P. gingivalis was found to co-exist with EBV in NPC tumor tissues, but is not etiologically relevant to NPC in non-endemic areas, such as Central China., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gu et al.)

With the rapid development of urbanization, heavy metal pollution of soil has received great attention. Over-enrichment of heavy metals in soil may endanger human health. Assessing soil pollution and identifying potential sources of heavy metals are crucial for prevention and control of soil heavy metal pollution. This study introduced a spatial distribution - principal component analysis (SD-PCA) model that couples the spatial attributes of soil pollution with linear data transformation by the eigenvector-based principal component analysis. By evaluating soil pollution in the spatial dimension it identifies the potential sources of heavy metals more easily. In this study, soil contamination by eight heavy metals was investigated in the Lintong District, a typical multi-source urban area in Northwest China. In general, the soils in the study area were lightly contaminated by Cr and Pb. Pearson correlation analysis showed that Cr was negatively correlated with other heavy metals, whereas the spatial autocorrelation analysis revealed that there was strong association in the spatial distribution of eight heavy metals. The aggregation forms were more varied and the correlation between Cr contamination and other heavy metals was lower. The aggregation forms of Mn and Cu, Zn and Pb, on the other hand, were remarkably comparable. Agriculture was the largest pollution source, contributing 65.5 % to soil pollution, which was caused by the superposition of multiple heavy metals. Additionally, traffic and natural pollution sources contributed 17.9 % and 11.1 %, respectively. The ability of this model to track pollution of heavy metals has important practical significance for the assessment and control of multi-source soil pollution., 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.)

Background: Recent studies indicated that the neutrophil percentage-to-albumin ratio (NPAR) was a predictor of mortality in several diseases. There has been no evidence to prove the predictive function of NPAR in patients with liver cirrhosis. Therefore, this study aimed to investigate the association between NPAR and clinical outcomes in cirrhotic patients., Methods: We retrospectively recruited hospitalized decompensated cirrhotic patients from the tertiary grade-A hospital. Patients with malignancy or severe cardiac, respiratory and kidney diseases were excluded. Demographical data, liver functions, complications and outcomes of cirrhosis were recorded. NPAR was calculated through the ratio of neutrophil percentage (%)/serum albumin concentration (g/dL) at admission to the hospital. Cox proportional hazards models were performed to evaluate the prognostic values of NPAR, and subgroup analyses were utilized to ensure stable results., Results: A total of 376 patients with decompensated liver cirrhosis at baseline were enrolled. The liver dysfunction, cirrhosis-related complications and mortality rate increased along with the tertiles of NPAR. In multivariate analysis, higher NPARs were independently associated with increased risk of mortality in patients with liver cirrhosis after adjustments for confounding factors (tertile 3 versus tertile 1: adjusted HR = 1.92; 95% CI, 1.04-3.56; P trend =  0.008) and each unit increase of NPAR implicated a 4% increase risk of mortality. Subgroup analysis demonstrated no significant interactions in most subgroups., Conclusion: Increased NPAR was independently correlated with a higher risk of mortality in patients with liver cirrhosis., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

RNA modification is a dynamic and reversible process regulated by a series of writers, erasers and readers (WERs). Abnormal changes of WERs will disrupt the RNA modification homeostasis of their target genes, leading to the dysregulation of RNA metabolisms such as RNA stability and translation, and consequently to diseases such as cancer. A public repository hosting the regulatory relationships between WERs and their target genes will help in understanding the roles of RNA modifications in various physiological and pathological conditions. Previously, we developed a database named 'm6A2Target' to host targets of WERs in m6A, one of the most prevalent RNA modifications in eukaryotic cells. To host all RNA modification (RM)-related WER-target associations, we hereby present an updated database, named 'RM2Target' (http://rm2target.canceromics.org/). In this update, RM2Target encompasses 1 619 653 WER-target associations for nine RNA modifications in human and mouse, including m6A, m6Am, m5C, m5U, m1A, m7G, pseudouridine, 2'-O-Me and A-to-I. Extensive annotations of target genes are available in RM2Target, including but not limited to basic gene information, RNA modifications, RNA-RNA/RNA-protein interactions and related diseases. Altogether, we expect that RM2Target will facilitate further downstream functional and mechanistic studies in the field of RNA modification research., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: This study aimed to estimate healthy life expectancy (HLE) regarding anxiety, depression and their comorbidity among rural older adults., Methods: A total of 12,851 subjects (5790 men and 7061 women) enrolled from the Henan Rural Cohort Study were used to evaluate healthy status expectancy (HSE), and 10,096 (4475 men and 5621 women) of them were used to estimate health-adjusted life expectancy (HALE). The life expectancy was calculated using period life table, and HSE and HALE indicators were calculated via the Sullivan method., Results: For participants aged 60, the depression-free life expectancy (DFLE), anxiety-free life expectancy (AFLE), and depression- and anxiety-free life expectancy (DAFLE) were 23.0993, 23.3314, and 22.7206 years, respectively. The quality-adjusted life expectancy (QALE) of those with neither anxiety nor depression, with anxiety, with depression, and with comorbidity was 22.0727, 20.8751, 18.1484, and 17.0823 years, respectively. The ratio of DFLE (AFLE) to LE increased with age among both genders, while the DAFLE/LE showed a decreasing trend. Regardless of HSE or HALE indicators, women tended to have higher HLE, while HLE/LE was lower than men. Furthermore, all HLE indicators associated with anxiety were the largest in both genders compared to indicators regarding depression., Limitations: The HLE may be overestimated ignoring institutional population in the study., Conclusion: Anxiety and depression played essential roles in the quality of life among rural older adults, especially depression. Comorbidity would intensify the adverse effect in rural areas, especially for older men. More attention should be paid to the psychological problems among rural older population., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The status and associated factors of the health-related quality of life of non-small-cell lung cancer (NSCLC) patients under targeted anti-cancer therapy have not been investigated. Self-management and coping style have been proven to be closely related to patients' health-related quality of life. Based on these observations, this study was designed to firstly assess the status of health-related quality of life, and then explore the relationships among coping styles, self-management, and health-related quality of life of NSCLC patients with skin adverse drug reactions under targeted therapy., Methods: We performed a cross-sectional study including 536 NSCLC patients with skin adverse drug reactions under targeted therapy in cancer clinics of three hospitals in China between May 2020 and May 2021. Structured questionnaires, including the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18, Cancer Patient Self-management Evaluation Scale, and Medical Coping Modes Questionnaire, were used to collect data. Relationships among coping style, self-management, and health-related quality of life were identified by Pearson correlation analysis and a multiple linear regression algorithm., Results: The total score of health-related quality of life was 46 ± 12.84 in 536 NSCLC patients with skin adverse drug reactions undergoing targeted therapy. Health-related quality of life was positively correlated with self-management (r = 0.785, P < 0.01) and facing (r = 0.807, P < 0.01) and negatively correlated with yield (r =  - 0.718, P < 0.01), avoidance (r =  - 0.711, P < 0.01), and the severity of skin adverse reactions (r =  - 0.722, P = 0.000). Via multiple linear regression analysis, we identified some significant factors associated with health-related quality of life, including age, education level, combination of medicine, Charlson Comorbidity Index, stages of disease, facing, yield, symptom management, daily activity management, psychological and emotional management, self-efficacy, and self-management (P < 0.05)., Conclusions: NSCLC patients with skin adverse drug reactions undergoing targeted therapy generally had a compromised health-related quality of life. The critical factors that were associated with the status of health-related quality of life were age, education level, comorbidity, the combinatorial application of drugs, stage of disease, self-management, and coping styles., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Here, we provide a feasible, well-designed protocol of a randomised controlled trial for the assessment of the effects of a home-based multidisciplinary intervention on the severity of skin adverse drug reactions and health-related indicators in patients with non-small cell lung cancer (NSCLC) under epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy., Methods and Analysis: The study will be a two-group, parallel randomised controlled trial conducted at patients' homes by a multidisciplinary team in Zhengzhou in Henan Province, China. Patients with NSCLC who received EGFR-TKI therapy and experienced adverse skin reactions will be randomised and receive either ordinary care or home-based multidisciplinary interventions. The intervention will be divided into an intensive stage (6 weeks) and a maintenance stage (6 weeks) with baseline and follow-up assessment. Interventions in the intensive stage will include general interventions such as health education, follow-up, behaviour guide and social support and targeted interventions such as skill training, coping with adverse drug reaction and problem-solving. The measures that will be carried out in maintenance stage are continuous interventions consisted of an intensive intervention. The multidisciplinary team will be responsible for managing skin adverse drug reactions as required at patients' homes. Data collection and analysis will be performed by researchers at baseline, the end of the sixth week of intervention and the third month after the intervention. The primary outcome is the degree of skin adverse drug reactions, while the secondary outcomes, for example, self-management ability, quality of life, outpatient visits and health economics indicators, will also be presented., Ethics and Dissemination: This study was reviewed and approved by the Ethics Committee of Zhengzhou University (No. ZZUIRB-2020-97). Findings will be available to patients, clinicians, nurses, pharmacists, community medical staff, funders and health policymakers through peer-reviewed publications, social media and patient support groups., Trial Registration Number: Chinese Clinical Trials Registry (ChiCTR2000040643)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Oxidative stress is one of the most important factors affecting large-scale breeding, especially the performance of pigs. Oxidative stress plays a role by affecting various genes in pigs, which can cause serious body damage, functional degradation and reduce production performance., Objective: The purpose of this study was to investigate the effect of Toll like receptor 9 (TLR9) pathway on IPEC-J2 cells under oxidative stress and to provide reference for the growth development of Dapulian pigs., Methods: In this study, Diquat was used as a source of oxidative stress to study the effects on Dapulian pigs by detecting relevant indicators. Then the IPEC-J2 cells were selected to verify the TLR9 signaling pathway in oxidative stress., Results: Compared with the control group, superoxide dismutase (SOD) in experimental group decreased significantly, malondialdehyde (MDA) was significantly increased, accompanied by inflammatory reaction, and inflammatory factors were significantly increased in the experimental group. Oxidative stress model was constructed by H2O2 incubating IPEC-J2 cells. The interference and overexpression vectors of TLR9 and myeloid differentiation primary response protein 88 (MyD88) were constructed to detect the activity of antioxidant enzymes and related proteins. The results showed that overexpression of TLR9 enhanced the activity of antioxidant enzymes, decreased the secretion of inflammatory factors, and decreased the activity of MDA，reactive oxygen species (ROS); the results were opposite after TLR9 interference. This study also showed that H 2 O 2 can activate the nuclear factor-κB (NF-κB) pathway and promote the translocation of NF-κB into the nucleus. After co-transfection with TLR9 and MyD88, the results showed that TLR9 regulated the expression of NF-κB through MyD88., Conclusion: The study showed that TLR9 pathway had a significant positive effect on antioxidant., (© 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Objective: The growth of pigs involves multiple regulatory mechanisms, and modern molecular breeding techniques can be used to understand the skeletal muscle growth and development to promote the selection process of pigs. This study aims to explore candidate lncRNAs and mRNAs related to skeletal muscle growth and development among Duroc pigs with different average daily gain (ADG)., Methods: A total of 8 pigs were selected and divided into two groups: H group (high-ADG) and L group (low-ADG). And followed by whole transcriptome sequencing to identify differentially expressed (DE) lncRNAs and mRNAs., Results: In RNA-seq, 703 DE mRNAs (263 up-regulated and 440 down-regulated) and 74 DE lncRNAs (45 up-regulated and 29 down-regulated) were identified. In addition, 1,418 Transcription factors (TFs) were found. Compared with mRNAs, lncRNAs had fewer exons, shorter transcript length and open reading frame length. DE mRNAs and DE lncRNAs can form 417 lncRNA-mRNA pairs (antisense, cis and trans). DE mRNAs and target genes of lncRNAs were enriched in cellular processes, biological regulation, and regulation of biological processes. In addition, quantitative trait locus (QTL) analysis was used to detect the functions of DE mRNAs and lncRNAs, the most of DE mRNAs and target genes of lncRNAs were enriched in QTLs related to growth traits and skeletal muscle development. In single-nucleotide polymorphism/insertion-deletion (SNP/INDEL) analysis, 1,081,182 SNP and 131,721 INDEL were found, and transition was more than transversion. Over 60% of percentage were skipped exon events among alternative splicing events., Conclusion: The results showed that different ADG among Duroc pigs with the same diet maybe due to the DE mRNAs and DE lncRNAs related to skeletal muscle growth and development.

Porcine skeletal muscle is a highly heterogeneous tissue type, and the Longissimus Dorsi muscle (LDM), as the most economical and physiologically metabolized skeletal muscle in pigs, has always been the focus of research and improvement in pig molecular breeding. Circular RNA, as an important new member of regulatory non-coding RNA after microRNA, has become a frontier hot spot in life science research. This study aims to explore candidate circRNAs related to growth, meat quality, and skeletal muscle development among Duroc pigs with different average daily gain (ADG). Eight pigs were selected and divided into two groups: H group (high-ADG) and L group (low-ADG), followed by RNA-Seq analysis to identify circRNAs. The results showed that backfat at 6-7 rib (BF) and Intramuscular fat (IMF) content in the H group was significantly lower than L group, but ribeye area (REA) in the H group was higher than in the L group. In RNA-seq, 296 Differentially expressed (DE) circRNAs (157 upregulated and 139 downregulated) were identified and exons flanking long introns are easier to circularize to produce circRNAs. Most of the DE circRNAs were enriched in Quantitative trait locus (QTL) regions related to meat quality and growth traits. In addition, a gene can produce one or more circRNA transcripts. It was also found that the source genes of DE circRNAs were enriched in MAPK, FoXO, mTOR, PI3K-Akt, and Wnt signaling pathways. The results showed that different ADG, carcass, and meat quality traits among half-sibling Duroc pigs with the same diet may be due to the DE circRNAs related to skeletal muscle growth and development., 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 Ma, Chen, Li, Qin and Zeng.)

Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently single-stranded closed loop structures derived from back-splicing event of linear precursor mRNAs (pre-mRNAs). N6-methyladenosine (m 6 A), the most abundant epigenetic modification in eukaryotic RNAs, has been shown to play a crucial role in regulating the fate and biological function of circRNAs, and thus affecting various physiological and pathological processes. Accurate identification of m 6 A modification in circRNAs is an essential step to fully elucidate the crosstalk between m 6 A and circRNAs. In recent years, the rapid development of high-throughput sequencing technology and bioinformatic methodology has propelled the establishment of a multitude of approaches to detect circRNAs and m 6 A modification, including in vitro-based and in silico methods. Based on this, the research community has started on a new journey to develop methods for identification of m 6 A modification in circRNAs. In this review, we provide a comprehensive review and evaluation of the existing methods responsible for detecting circRNAs, m 6 A modification, and especially, m 6 A modification in circRNAs, which mainly focused on those developed based on high-throughput technologies and methodology of bioinformatics. This handy reference can help researchers figure out towards which direction this field will go., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD)., Methods: Thirty-one patients with RR-MADD admitted to our hospital from January 2005 to November 2020 were enrolled, and their clinical data were collected. Pathological characteristics of the muscle tissue and possible pathogenic gene mutations were analyzed., Results: The most common clinical features in all patients were symmetrical proximal muscle weakness. Laboratory examination revealed elevated levels of creatine kinase, homocysteine, and uric acid, acylcarnitines, and organic acid. The muscle biopsy revealed typical pathological changes like lipid deposition. Genetic analysis identified ETFDH mutations in 29 patients, among which one had homozygotes, 19 had compound heterozygotes, 7 had heterozygous mutations, and 2 had heterozygous mutations of both ETFDH and ETFA. Two patients had no pathogenic gene mutations. All patients were treated with riboflavin, and their symptoms improved, which was consistent with the diagnosis of RR-MADD., Conclusion: The clinical manifestations and genetic test results of patients with RR-MADD are heterogeneous. Therefore, a comprehensive analysis of clinical, pathological, and genetic testing is essential for the early diagnosis of RR-MADD.

In this study, we mainly focus on probing expression profile and detailed functions of long non-coding RNA TFAP2A antisense RNA 1 (TFAP2A-AS1) in non-small cell lung cancer (NSCLC). Moreover, the mechanisms played by TFAP2A-AS1 were unraveled comprehensively. Herein, a notable overexpressed TFAP2A-AS1 in NSCLC was observed by TCGA and our own cohort. An increased TFAP2A-AS1 level displayed a negative correlation with the overall survival of patients with NSCLC. Loss-of-function approaches illustrated that the absence of TFAP2A-AS1 weakened NSCLC cell proliferation, colony formation, migration and invasion in vitro . Also, interference of TFAP2A-AS1 caused in vivo tumor growth suppression. Mechanistically, TFAP2A-AS1 could negative regulate microRNA-584-3p (miR-584-3p) as a competitive endogenous RNA. Furthermore, cyclin-dependent kinase 4 (CDK4), a direct target of miR-584-3p, was positively controlled by TFAP2A-AS1 in a miR-5184-3p-dependent manner. Rescue function experiments corroborated that the anticancer activities of TFAP2A-AS1 deficient on the oncogenicity of NSCLC cells were reversed by downregulating miR-584-3p or overexpressing CDK4. To sum up, TFAP2A-AS1 exhibits cancer-promoting roles in NSCLC through the adjustment of miR-584-3p/CDK4 axis., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2021 Zhang et al.)

Objective: To explore the experience of non-small-cell lung cancer patients with targeted therapy-related skin adverse drug reactions., Methods: This is a descriptive quantitative study conducted in a comprehensive hospital in Henan, China. Purposive sampling was used to recruit patients with non-small-cell lung cancer and with targeted therapy-related skin adverse drug reactions. In total, 23 patients were approached when the data were saturated. Face-to-face interviews were conducted by an independent researcher using a semi-structured interview guide. Interview data were transcribed and analyzed by qualitative inductive content analysis., Results: Based on the analysis, four main categories were identified according to patients' descriptions of their experience: a lack of self-management ability, psychological and emotional problems, a barrier to social participation, and a need for social support. Suffering from persistent symptoms, insufficient knowledge, skills and strategies for skin adverse drug reaction management, psychological problems, social avoidance/withdrawal, and reduced willingness to work were core experiences that would affect patients' compliance with treatment, prognosis, and the overall quality of life., Conclusions: This study revealed the real experience of patients with non-small-cell lung cancer and with targeted therapy-related skin adverse drug reactions which contributed to the development of targeted interventions to manage skin adverse reactions., (© 2022 The Author(s).)

Base editing has emerged as a revolutionary technology for single nucleotide modifications. The cytosine and adenine base editors (CBEs and ABEs) have demonstrated great potential in clinical and fundamental research. However, screening and isolating target-edited cells remains challenging. In the current study, we developed a universal Adenine and Cytosine Base-Editing Antibiotic Resistance Screening Reporter (ACBE-ARSR) for improving the editing efficiency. To develop the reporter, the CBE-ARSR was first constructed and shown to be capable of enriching cells for those that had undergone CBE editing activity. Then, the ACBE-ARSR was constructed and was further validated in the editing assays by four different CBEs and two versions of ABE at several different genomic loci. Our results demonstrated that ACBE-ARSR, compared to the reporter of transfection (RoT) screening strategy, improved the editing efficiency of CBE and ABE by 4.6- and 1.9-fold on average, respectively. We found the highest CBE and ABE editing efficiencies as enriched by ACBE-ARSR reached 90% and 88.7%. Moreover, we also demonstrated ACBE-ARSR could be employed for enhancing simultaneous multiplexed genome editing. In conclusion, both CBE and ABE activity can be improved significantly using our novel ACBE-ARSR screening strategy, which we believe will facilitate the development of base editors and their application in biomedical and fundamental research studies., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, we mainly focus on probing expression profile and detailed functions of long non coding RNA TFAP2A antisense RNA 1 (TFAP2A AS1) in non small cell lung cancer (NSCLC). Moreover, the mechanisms played by TFAP2A AS1 were unraveled comprehensively. Herein, a notable overexpressed TFAP2A AS1 in NSCLC was observed by TCGA and our own cohort. An increased TFAP2A AS1 level displayed a negative correlation with the overall survival of patients with NSCLC. Loss of function approaches illustrated that the absence of TFAP2A AS1 weakened NSCLC cell proliferation, colony formation, migration and invasion in vitro. Also, interference of TFAP2A AS1 caused in vivo tumor growth suppression. Mechanistically, TFAP2A AS1 could negative regulate microRNA 584 3p (miR 584 3p) as a competitive endogenous RNA. Furthermore, cyclin dependent kinase 4 (CDK4), a direct target of miR 584 3p, was positively controlled by TFAP2A AS1 in a miR 5184 3p dependent manner. Rescue function experiments corroborated that the anticancer activities of TFAP2A AS1 deficient on the oncogenicity of NSCLC cells were reversed by downregulating miR 584 3p or overexpressing CDK4. To sum up, TFAP2A AS1 exhibits cancer promoting roles in NSCLC through the adjustment of miR 584 3p/CDK4 axis.

Background: High medication literacy is the basis of rational medication application and is essential for the management of severe adverse drug reactions. The objective of the present study was to assess the level of medication literacy and determine the association between medication literacy and skin adverse drug reactions in non-small-cell lung cancer (NSCLC) patients undergoing targeted epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy., Methods: This is a cross-sectional study conducted from May to September 2020. In total, 296 NSCLC patients undergoing targeted EGFR-TKI therapy were recruited from hospitals in Henan, China. Structured questionnaires were used to evaluate skin adverse drug reactions and medication literacy. Pearson correlation analysis and binary logistic regression analysis were carried out to identify the correlations between medication literacy and the severity of skin adverse drug reactions in the recruited patients., Results: The research sample consisted of 296 patients with a response rate of 92.5%. The mean score of skin adverse drug reactions and the mean score of medication literacy were 1.83 ± 0.91 and 6.54 ± 2.78, respectively. In total, 188 patients (63.5%) were considered to have moderate medication literacy. According to the binary logistic regression analysis, the following factors were associated with severe skin adverse drug reactions: age (B =  - 3.929, P = 0.000), sex (B = -4.062, P = 0.000), educational level (B = 2.712, P = 0.002), comorbidity (B = 3.297, P = 0.001), eczema history (B = 2.996, P = 0.001), nutritional status (B = -4.891, P = 0.000), blood interleukin-6 level (B = -2.143, P = 0.013), blood high-sensitivity C-reactive protein level (B = -4.015, P = 0.000), combination of drugs (B = -3.183, P = 0.048) and medication literacy (B =  - 1.503, P = 0.000). Subgroup analysis showed that in addition to medication literacy, some other factors including education level, comorbidity, nutritional status, blood interleukin-6 level and combined drug application were common factors that contributed to various adverse skin drug reactions in NSCLC patients under targeted EGFR-TKI therapy., Conclusion: The low medication literacy of the investigated NSCLC patients undergoing targeted EGFR-TKI therapy was correlated with a high proportion of severe skin adverse drug reactions. In addition, factors other than medication literacy including education level, comorbidity, nutritional status, blood interleukin-6 level and the combinatorial application of drugs were also related to the severity of various adverse skin drug reactions. A comprehensive and targeted intervention may be beneficial to improve medication literacy and control severe skin adverse drug reactions in NSCLC patients., (© 2022. The Author(s).)

High-performance quantum memory for quantized states of light is a prerequisite building block of quantum information technology. Despite great progresses of optical quantum memories based on interactions of light and atoms, physical features of these memories still cannot satisfy requirements for applications in practical quantum information systems, since all of them suffer from trade-off between memory efficiency and excess noise. Here, we report a high-performance cavity-enhanced electromagnetically-induced-transparency memory with warm atomic cell in which a scheme of optimizing the spatial and temporal modes based on the time-reversal approach is applied. The memory efficiency up to 67 ± 1% is directly measured and a noise level close to quantum noise limit is simultaneously reached. It has been experimentally demonstrated that the average fidelities for a set of input coherent states with different phases and amplitudes within a Gaussian distribution have exceeded the classical benchmark fidelities. Thus the realized quantum memory platform has been capable of preserving quantized optical states, and is ready to be applied in quantum information systems, such as distributed quantum logic gates and quantum-enhanced atomic magnetometry., (© 2022. The Author(s).)

The Argonaute proteins are present in all three domains of life, which are archaea, bacteria, and eukarya. Unlike the eukaryotic Argonaute proteins, which use small RNA guides to target mRNAs, some prokaryotic Argonaute proteins (pAgos) use a small DNA guide to interfere with DNA and/or RNA targets. However, the mechanisms of pAgo natural function remain unknown. Here, we investigate the mechanism by which pAgo from Natronobacterium gregoryi (NgAgo) targets plasmid and bacteriophage T7 DNA using a heterologous Escherichia coli-based model system. We show that NgAgo expressed from a plasmid linearizes its expression vector. Cotransformation assays demonstrate that NgAgo requires an RNA in trans that is transcribed from the bacteriophage T7 promoter to activate cleavage of a cotransformed plasmid, reminiscent of the trans -RNA function in CRISPR/Cas9. We propose a mechanism to explain how NgAgo eliminates invading foreign DNA and bacteriophage. By leveraging this discovery, we show that NgAgo can be programmed to target a plasmid or a chromosome locus. IMPORTANCE We revealed the mechanism that explains how the NgAgo eliminates the invading foreign DNA and bacteriophage in bacterial cells at 37°C, and by leveraging this discovery, NgAgo can be programmed to target a plasmid or a chromosome locus.

Cirrhotic cardiomyopathy (CCM) is a recognized complication of cirrhosis and is associated with poor outcomes, especially under challenges such as surgery/liver transplantation. However, the mechanism is not clear, and the treatment is not specific. The present study aimed to evaluate the role of anti-β 1 -adrenergic receptor antibodies (anti-β1-AR) in CCM. We enrolled 3 groups: healthy controls, cirrhotic patients without CCM, and patients with CCM. We found that the anti-β1-AR levels in the CCM group were significantly higher than that in the non-CCM group; anti-β1-AR was positively correlated to NT-proBNP, negatively correlated to left ventricular ejection fraction, fractional shortening ((r =  - 0.466, P < 0.05), and the ratio of peak early (E wave) and atrial (A wave) flow velocities (E/A (r =  - 0.475, P < 0.05) in CCM patients. Anti-β1-AR is a useful predictive biomarker for the presence of CCM and eventually may also have therapeutic implications. Clinical Trials Registration: Chinese Clinical Trials No. ChiCTR 2,000,037,730., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The objectives of the present study were to explore the epidemiological characteristics of hypertension among rural older adults in resource-limited regions, and then evaluate the loss of health-adjusted life expectancy due to hypertension., Methods: Participants aged between 60 and 79 years were enrolled from Henan rural cohort study. The prevalence, awareness, treatment, and control of hypertension were detailed across subgroups. Variances within subgroups were identified via Student's t tests or one-way ANOVA for continuous variables and chi-squared tests for categorical ones, and logistic regression model was employed to detect the potential influencing factors. The health-adjusted life expectancy was calculated by the Sullivan method with EuroqOL-5D data., Results: Among 16,785 participants, 7,472 (44.52%) were attacked by hypertension, 4,858 (65.02%) had been already aware of their condition, 4,009 (53.65%) were taking antihypertensive medication for treatment, while only 1,478 (19.78%) had their hypertension controlled. The prevalence of hypertension was significantly higher among women than men and it increased with age for both genders. For the older ones aged 60 years, the life expectancy was 22.0872 years and the health-adjusted life expectancy was 15.5578 and 15.9418 for those with or without hypertension, respectively. Namely, in this particular age group, subjects without hypertension could gain 0.3840 years of health-adjusted life expectancy., Conclusion: The prevalence of hypertension was relatively high while the awareness, treatment, and control were fairly low. The health-adjusted life expectancy of older adults in resource-limited areas could increase from the reduction of hypertension. There is an urgent need for strategies pertaining to the prevention and treatment of hypertension., Clinical Trial Registration: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375., 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 Hu, Liu, Liao, Kang, Ma, Mao, Hou, Huo, Li and Wang.)

The development of nonprecious metal-based electrocatalysts for oxygen reduction reaction (ORR) is a central task in renewable electrochemical energy conversion and storage technologies. Iron-nitrogen doped carbon-based (Fe-N/C) materials are promising alternatives to Pt-based ORR electrocatalysts. Owing to large specific surface area and outstanding electrical conductivity, carbon black is an inborn support for electrocatalysts. Unfortunately, the direct incorporation of Fe-N x moieties onto the surface of carbon black has not been realized to date. Herein, Fe-N x moieties are directly incorporated onto the surface of carbon black through surface modification and the following Fe and N co-doping. The obtained Fe and N co-doped carbon back (Fe-N/CB) catalyst has very large specific surface area and abundant accessible Fe-N x moieties. As a result, Fe-N/CB electrocatalyst exhibits a more positive half-wave potential (0.86 V) than Pt/C. The Fe-N/CB catalyst also displays better stability and methanol resistance than Pt/C. The Zn-air battery with Fe-N/CB as cathodic catalyst shows a maximum power density of 68 mW cm -2 and a specific capacity of 676 mAh g Zn -1 . Our finding provides a convenient and low-cost approach to fabricating efficient M-N/C-based catalysts and will be helpful to the development of renewable electrochemical energy conversion and storage technologies., 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 © 2021 Elsevier Inc. All rights reserved.)

Graphitic carbon nitride (CN) generally needs to be exfoliated into ultrathin nanosheets to reduce photocarrier recombination. However, the exfoliation of CN into nanosheets also reduces the light absorption. How to simultaneously realize low photocarrier recombination and high light absorption remains a challenge in the practical application of CN in photocatalysis. Herein, the light absorption of CN nanosheets was enhanced by introducing hollow TiO 2 (h-TiO 2 ) dielectric resonators. The h-TiO 2 /CN heterostructures were prepared by thermally polymerizing dicyandiamide in the presence of h-TiO 2 . The electromagnetic resonances of the h-TiO 2 resonator creates strong electric field enhancement within, inside, and near external surface of the introduced h-TiO 2 nanoshells. The enhanced electric field greatly improves the light absorption of CN located in these regions. The largest hydrogen evolution rate for h-TiO 2 /CN can reach 6.3 mmol g -1 h -1 , which is over 3-fold that of pure CN (2.0 mmol g -1 h -1 ). It is also found that the small amount of CN within and inside h-TiO 2 majorly contributes to the photocatalytic performance. These findings open a new avenue by which to enhance the performance of photocatalysts and will be helpful in the design of highly efficient photocatalysts for various reactions., 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 © 2021 Elsevier Inc. All rights reserved.)

Objective: To analyze and compare the diagnostic value of nuclear medicine and ultrasonography in subacute thyroiditis., Methods: Sixty patients with subacute thyroiditis admitted to our hospital were included into the observation group, and 60 healthy controls who underwent physical examination in our hospital during the same period were enrolled into the control group. Examinations of nuclear medicine and ultrasonography were performed in the neck, and the results were compared between the two groups., Results: There were significant differences in the width and thickness of thyroid bilateral lobes between the two groups (P<0.05), and for patients in the observation group, the detection rates of nuclear medicine technique and ultrasonography were 98.33% and 95.00%, respectively. Both methods showed no significant difference in the detection rate of subacute thyroiditis (P>0.05)., Conclusion: Both nuclear medicine imaging and ultrasonography can provide clinical guidance for diagnosis and treatment of subacute thyroiditis., Competing Interests: None., (AJTR Copyright © 2021.)

Background: Interferon lambda receptor 1 ( IFNLR1 ) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear., Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV)., Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods., Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV., Conclusion: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Veterinary Science.)

The prokaryotic Argonaute proteins (pAgos) have been reported to cleave or interfere with DNA targets in a guide-dependent or independent manner. It is often difficult to characterize pAgos in vivo due to the extreme environments favored by their hosts. In the present study, we expressed functional Thermus thermophilus pAgo (TtAgo) in E. coli BL21 (DE3) cells at 37 °C. Initial attempts to express TtAgo in BL21(DE3) cells at 37 °C failed. This was not because of TtAgo mediated general toxicity to the host cells, but instead because of TtAgo-induced loss of its expression plasmid. We employed this discovery to establish a screening system for isolating loss-of-function mutants of TtAgo. The E. coli fabI gene was used to help select for full-length TtAgo loss of function mutants, as overexpression of fabI renders the cell to be resistant to the triclosan. We isolated and characterized eight mutations in TtAgo that abrogated function. The ability of TtAgo to induce loss of its expression vector in vivo at 37 °C is an unreported function that is mechanistically different from its reported in vitro activity. These results shed light on the mechanisms by which TtAgo functions as a defense against foreign DNA invasion.

Background: The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data., Methods: A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups., Results: A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group., Conclusion: The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

The interface between two material phases typically exhibits unique electronic states distinct from their pure phases, thus, providing a very promising channel to construct catalysts with excellent activity and stability. Here, water-induced formation of Ni 2 P-Ni 12 P 5 through a one-step phosphorization of nickel foam (NF) is demonstrated for the first time. The abundant interfaces endow Ni 2 P-Ni 12 P 5 /NF with excellent electrocatalytic hydrogen evolution reaction (HER) activity in alkaline condition, with an overpotential of 76 mV at a current density of 10 mA cm -2 and of 147 mV at a current density of 100 mA cm -2 , and a Tafel slope of 68.0 mV dec -1 . The Ni 2 P-Ni 12 P 5 /NF also exhibits better durability than Pt/C/NF during HER at relatively large overpotential. Density functional theory calculations show that the electronic states at the Ni 2 P-Ni 12 P 5 interface are greatly altered, which enables optimal hydrogen adsorption, accelerates the charge transfer kinetics, and thus enhances the HER electrocatalytic activity. Superior overall water-splitting performance is also obtained by combining Ni 2 P-Ni 12 P 5 /NF with NiFe-layered double hydroxide (LDH) oxygen evolution reaction (OER) catalyst. Overpotentials of the cell for achieving 10 mA cm -2 are only 324 mV. This work provides a facile method for the preparation of interfaces between different nickel phosphide polymorphs toward HER., (© 2021 Wiley-VCH GmbH.)

Objectives: The present study aimed to determine the status of a universal newborn hearing screening (UNHS) program being conducted in parts of China, by comparing differences in the program findings between 2016 and 2017, as well as across regions in China., Methods: This study investigated a nationally representative sample of newborns from 26 provinces, autonomous regions, and municipalities in mainland China. A ''Newborn Hearing Screening Survey'' questionnaire was sent to 43 hearing screening institutions throughout China and the data were analyzed, with appropriate quality control throughout the study process., Results: Twenty-six questionnaires, covering 55.88% (19/34) of the provincial administrative regions in China were appropriately completed. The overall sampling frame comprised 238,795 (year 2016) and 229,185 (year 2017) newborns, respectively. We found differences between two years, the initial screening coverage in 2017 (96.10%) was higher than that in 2016 (94.96%); the referral rate at initial screening in 2017 (9.21%) was lower than that in 2016 (10.26%); and the rescreening rate in 2017 (73.50%) was higher than that in 2016 (68.44%). We found differences across three regions, the rescreening rate were highest in West China, the referral rate at rescreening and the referral rate to diagnostic audiological assessment diagnosis were both highest, while the hearing-loss rate was lowest, in the East China in two years. Overall, 61.54% (n = 16) reported using otoacoustic emissions (OAEs), while 38.46% (n = 10) reported using OAEs in combination with automated auditory brainstem response (AABR) tests, for the initial screening. For rescreening, most sites (n = 19, 73.08%) reported using OAEs in combination with AABR, followed by OAEs only (n = 4, 15.38%) and AABR only (n = 3, 11.54%). Of the twenty-six institutions, 57.69% (n = 15) were equipped with a digital information management system for UNHS program, East China had the highest rate of it (81.82%, 9/11)., Conclusions: This study indicated that implementation of a UNHS program had essentially been achieved in many regions of China under the guidance of technical specifications for newborn hearing screening. Compared with 2016, the overall quality of the UNHS program had improved in 2017 and that in East China was better than in the Midland and West China. However, national quality control of the UNHS program is still required to enhance the quality of the program and public education needs to be emphasized to improve the rescreening and reception rate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The α-Fe 2 O 3 /graphite composites were prepared by a thermal decomposition method using the expanded graphite as the matrix. The α-Fe 2 O 3 nanoparticles with the size of 15-30 nm were embedded into interlayers of graphite, forming a laminated porous nanostructure with a main pore distribution from 2 to 20 nm and the Brunauer-Emmett-Teller surface area of 33.54 m 2 g -1 . The porous structure constructed by the graphite sheets can alleviate the adverse effects caused by the huge volume change of the α-Fe 2 O 3 grains during the charge/discharge process. The composite electrode exhibits a high reversible capacity of 1588 mAh g -1 after 100 cycles at 100 mA g -1 , 702 mAh g -1 at 5 A g -1 , 460 mAh g -1 at 10 A g -1 after 160 cycles, respectively, showing good cycle stability and outstanding rate capability at high current densities.

The needing of rapid and sensitive detection method for pesticides is increasing, to facilitate its detection without complicated instruments. Herein, a novel paper-based senor was developed for the visual detection of three carbamate pesticides (metolcarb, carbofuran, and carbaryl) based on CdTe quantum dots (QDs) and nano zinc 5, 10, 15, 20-tetra(4-pyridyl)-21H-23H-porphine (nano ZnTPyP) with a "turn-off-on" mode. This fluorescence sensing model could be applied in the highly selective and sensitive detection of carbamate pesticides both by fluorescence spectrometry or paper-based sensors. Based on the extracted RGB color values of paper, the partial least squares regression (PLSR) was used to accurately quantify the concentrations of carbamate pesticides in different food matrices (apple, cabbage and tea water). This method featured in high speed, low price and high accuracy, and provided a new strategy for the detection of food safety., 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.)

Objective: NTRK mutations and clinicopathological factors in patients with lung cancer in northeast China were analyzed by next-generation sequencing (NGS), and references were provided for patients with NTRK mutations undergoing targeted therapy in northeast China., Methods: A total of 224 specimens in 173 patients with lung cancer were collected. This included 51 patients with matched tissue and whole blood samples,133 tissue samples, 84 whole blood samples, and 7 pleural effusion samples. NGS (520 genes) was used to detected NTRK mutations and clinicopathologic factors., Results: NTRK mutation was detected in eight patients (8/173, 4.6%), including four NTRK missense mutations (4/173, 2.3%), two NTRK fusion gene mutations (2/173, 1.2%), and two NTRK copy number deletions (2/173, 1.2%). Among the eight patients with NTRK mutations, four were associated with lung cancer driver gene mutations (3/4 EGFR, 1/4ALK); NTRK in two patients was inconsistent in tissue and paired whole blood testing; NTRK missense mutation was detected in one patient, and NTRK copy number deletion was detected in the other; and NTRK wild type was detected in two patients. There was no correlation between NTRK mutation and clinicopathologic factors (including gender, age, pathological type, smoking status, metastasis site)., Conclusion: NTRK mutation was only 4.6%, effective fusion gene mutation was 1.2%, and common driver gene mutation in lung cancer was evident in 50% of patients. The results of NTRK were inconsistent with matched tissues and whole blood. Therefore, patients with NTRK mutation should use a variety of specimen types and large target area sequencing (panel) analysis method to provide individualized treatment.

Objectives: Although the majority of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients respond to EGFR tyrosine kinase inhibitors (TKIs), significant heterogeneity in clinical response is observed which might be attributed to the distinct sub-molecular characteristics. The present study aims to identify genetic alterations correlated with clinical outcomes and treatment response to different EGFR-TKI inhibitors., Materials and Methods: We integrated the genomic data and clinical outcomes including progression-free survival (PFS) and overall survival (OS) in 179 patients with advanced EGFR-mutant NSCLC who were treated with EGFR-TKI as 1st line of treatment., Results: We found that EGFR-mutant patients harboring concomitant TP53 mutation (OS: 21 vs. 40 months, P = 0.05), ERBB2 amplification (PFS: 6.1 vs. 12.5 months, P = 0.01) or FGF19 amplification (OS: 11.2 vs. 27.1 months, P = 0.01) were significantly associated with a poorer clinical prognosis after treated with 1st generation EGFR-TKI. In contrast, the presence of TP53 mutation did not affect the PFS nor OS of patients treated with 2nd generation EGFR-TKI. Furthermore, EGFR-mutant and TP53-wild type (WT) patients benefited more from a combinatorial treatment consisting of EGFR-TKI and bevacizumab comparing to EGFR-TKI as a single agent (PFS: 21.7 vs. 9.3 months, P < 0.01). Copy number variation (CNV) (PFS: 4.6 vs.9.4 months, p = 0.018) was identified as an unfavorable predictive factor to 3rd-generation TKI. We also revealed distinct resistance mechanisms associated with different EGFR-TKIs., Conclusion: Our study highlights the heterogeneity both in the primary molecular landscape and acquired alterations in EGFR-mutated NSCLCs, which might play a role in determining the clinical efficacy of EGFR-TKIs. We also revealed the differential prognostic role of TP53 mutation in patients treated with the 1st or 2nd generation of EGFR-TKI. Our study also suggests that EGFR-mutant and TP53-WT patients may benefit more from combinatorial treatment consisting of EGFR-TKI and bevacizumab, highlighting the importance of further stratifying EGFR-mutant patients., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Return to work following myocardial infarction (MI) represents an important indicator of recovery. However, MI can cause patients to feel pressure, loneliness and inferiority during work and even detachment from employment after returning to work, which may affect their quality of life. The aims of this study were to identify the influencing factors of Health-related quality of life (HRQoL) in patients with MI after returning to work and explore the correlations between these factors and HRQoL., Method: This was a cross-sectional study. All participants were recruited from tertiary hospitals in China from October 2017 to March 2018. The general data questionnaire, Short-Form Health Survey-8 (SF-8), Health Promoting Lifestyle ProfileII (HPLPII), Medical Coping Modes Questionnaire (MCMQ) and Social Supporting Rating Scale (SSRS) were used to assess 326 patients with myocardial infarction returned to work after discharge. Multiple linear regression analysis was performed to explore factors related to HRQoL in patients with MI after returning to work., Results: The sample consisted of 326 patients. The mean total score of quality of life was 28.03 ± 2.554. According to the multiple linear regression analysis, next factors were associated with better HRQoL: younger age (B = - 0.354, P = 0.039), higher income (B = 0.513, P = 0.000), less co-morbidity (B = - 0.440, P = 0.000), the longer time taken to return to work (B = 0.235, P = 0.003), fewer stents installed (B = - 0.359, P = 0.003), participation in cardiac rehabilitation (CR) (B = - 1.777, P = 0.000), complete CR (B = - 1.409, P = 0.000), better health behaviors such as more health responsibility (B = 0.172, P = 0.000) and exercise (B = 0.165, P = 0.000), better nutrition (B = 0.178, P = 0.000) and self-realization (B = 0.165, P = 0.000), stress response (B = 0.172, P = 0.000), more social support such as more objective support (B = 0.175, P = 0.000), subjective support (B = 0.167, P = 0.000) and better utilization of social support (B = 0.189, P = 0.028), positive copping strategies such as more coping (B = 0.133, P = 0.000) and less yield (B = - 0.165, P = 0.000)., Conclusions: HRQoL of MI patients after returning to work is not satisfactory. Health behavior, coping strategies, social support are factors which can affect HRQoL. A comprehensive and targeted guide may be a way to improve HRQoL and to assist patients' successful return to society.

Cell differentiation within an isogenic population allows the specialisation of subpopulations and a division of labour. Bacillus thuringiensis is a spore-forming bacterium that produces insecticidal crystal proteins (Cry proteins) in sporulating cells. We recently reported that strain B. thuringiensis LM1212 presents the unique ability to differentiate into two subpopulations during the stationary phase: spore-formers and crystal-producers. Here, we characterised the transcriptional regulator CpcR responsible for this differentiation and the expression of the cry genes. cpcR is located on a plasmid that also harbours cry genes. The alignment of LM1212 cry gene promoters revealed the presence of a conserved DNA sequence upstream from the -35 region. This presumed CpcR box was also found in the promoter of cpcR and we showed that cpcR transcription is positively autoregulated. Electrophoretic mobility shift assays suggested that CpcR directly controls the transcription of its target genes by binding to the CpcR box. We showed that CpcR was able to direct the production of a crystal consisting of a heterologous insecticidal Cry protein in non-sporulating cells of a typical B. thuringiensis kurstaki strain. Moreover, the expression of cpcR induced a reduction in the sporulation of this B. thuringiensis strain, suggesting an interaction between CpcR and the sporulation regulatory networks., (© 2019 John Wiley & Sons Ltd.)