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Xiaokai Yan,1,* Haifeng Wan,1 Xiangyong Hao,2 Tian Lan,1 Wei Li,1 Lin Xu,1,3 Kefei Yuan,1,3,* Hong Wu1,3 1Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China; 2Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China; 3Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China *These authors contributed equally to this work Background and aim: Pancreatic cancer (PC) is one of the most common tumors with a poor prognosis. The current American Joint Committee on Cancer (AJCC) staging system, based on the anatomical features of tumors, is insufficient to predict PC outcomes. The current study is endeavored to identify important prognosis-related genes and build an effective predictive model. Methods: Multiple public datasets were used to identify differentially expressed genes (DEGs) and survival-related genes (SRGs). Bioinformatics analysis of DEGs was used to identify the main biological processes and pathways involved in PC. A risk score based on SRGs was computed through a univariate Cox regression analysis. The performance of the risk score in predicting PC prognosis was evaluated with survival analysis, Harrell’s concordance index (C-index), area under the curve (AUC), and calibration plots. A predictive nomogram was built through integrating the risk score with clinicopathological information. Results: A total of 945 DEGs were identified in five Gene Expression Omnibus datasets, and four SRGs (LYRM1, KNTC1, IGF2BP2, and CDC6) were significantly associated with PC progression and prognosis in four datasets. The risk score showed relatively good performance in predicting prognosis in multiple datasets. The predictive nomogram had greater C-index and AUC values, compared with those of the AJCC stage and risk score. Conclusion: This study identified four new biomarkers that are significantly associated with the carcinogenesis, progression, and prognosis of PC, which may be helpful in studying the underlying mechanism of PC carcinogenesis. The predictive nomogram showed robust performance in predicting PC prognosis. Therefore, the current model may provide an effective and reliable guide for prognosis assessment and treatment decision-making in the clinic. Keywords: risk score, nomogram, TCGA, GEO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbs are a valuable source of novel antibacterials in combating pathogenic isolates of methicillin-resistant Staphylococcus aureus (MRSA), a global nosocomial problem. AIM OF THE STUDY: To assess in vitro anti-MRSA activity of extracts from Chinese herbs. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined in the setting of clinical MRSA isolates. MATERIALS AND METHODS: A collection of 19 plant extracts were obtained and bioassay-guided phytochemical analysis performed. Antibacterial susceptibilities were screened for inhibitory zone and MICs/MBCs determined by serial dilution with a standardized microdilution broth methodology. 9 MRSA isolates and a standard control strain (ATCC 25923) were cultured and exposed to the plant extract and isolated compound. Vancomycin was used as a positive control agent. RESULTS: All the presented 19 plants showed anti-MRSA activity with MIC of 1.25-3.07mg/ml. The most active antimicrobial plants were Dendrobenthamia capitata, Elsholtzia rugulosa, Elsholtzia blanda, Geranium strictipes and Polygonum multiflorum (MIC< or =1.43mg/ml), and betulinic acid isolated from the active ethyl acetate fraction of Dendrobenthamia capitata extract was determined with MIC/MBC values as 62.5/125.0mg/ml. CONCLUSIONS: Dendrobenthamia capitata, Elsholtzia rugulosa, Elsholtzia blanda, Geranium strictipesPolygonum multiflorum and betulinic acid demonstrate promising anti-MRSA potential. [ABSTRACT FROM AUTHOR]

Introduction: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study., Methods: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume., Results: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk., Conclusion: In summary, we consider there to be a substantial correlation between anemia and increased PD risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs)., Design: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related β-galactosidase (SA-β-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry., Results: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-β-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05)., Conclusions: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Patients who underwent arterio-arterial graft (AAG) surgery at Beijing Haidian Hospital from March 2021 to December 2023 were prospectively included. A total of 13 cases (6 males and 7 females) aged (59±13) years were collected, with a dialysis history of 4.0 (1.8, 10.0) years. Nine cases of "bow"-type AAG and 4 cases of "α"-type AAG were established. The follow-up time was 10 (7, 16) months. The primary patency and secondary patency rates at 3, 6 and 12 months after surgery were 92.3% and 100%, 81.8% and 90.9%, 57.1% and 57.1%, respectively. Stenosis, thrombosis and infection occurred in 2, 5 and 2 cases, respectively. The current study indicates that AAG surgery is simple, minimally invasive, and has a high long-term patency rate. It can be used as a new type of vascular access for patients who fail to establish conventional dialysis access.

Microorganisms produce extracellular enzymes to meet elemental requirements and cope with stoichiometric imbalances of resources. To gain insights into the cycling of C, N, and P, the activities of the C∶N∶P acquisition enzymes have been extensively investigated. To detect the effects of long-term fertilization practices on soil nutrient balance and characteristics of soil enzymatic stoichiometry in black soil, four different fertilization treatments were selected： no fertilization （CK）, nitrogen fertilizer （N）, phosphorus fertilizer （P）, and combination of nitrogen and phosphorus fertilizers （NP）. Soil samples were collected in both April 2021 and April 2022 to determine soil enzyme activities and their stoichiometric characteristics. The results showed that soil acid phosphatase and β -D-glucosidase activities were significantly higher in the N and NP treatments than in CK by 68%-158% and 26%-222%, respectively. Soil β -N-acetylaminoglucosidase activities were significantly higher in the P and NP treatments, with the highest around 75.48 nmol·（g·h） -1 and 106.81 nmol·（g·h） -1 , respectively. Two-way ANOVA analysis showed that N and P inputs had a great impact on soil enzyme activities. Redundancy analysis showed that the main factors controlling enzyme activities were soil pH, microbial biomass phosphorus, and soil available P content. It was found that N inputs significantly increased enzyme vector length, which was ranged from 1.32 to 1.52, and the enzyme vector angles were all larger than 45°, suggesting C and P co-limited in the black soils. These findings suggest that 40 years of fertilization have had a great impact on soil enzymes and the related resource use strategy, which provides great implications for assessing soil nutrients balance and soil sustainability.

Background: Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate worldwide. The unfavorable prognosis of OC is mainly attributed to the recurrent propensity. Recently, mortality from OC has exhibited a downward trend. These favorable patterns are likely to be driven by advancements in novel therapeutic regimens. However, there is a lack of visualize analysis of the application of these new drugs on women with recurrent OC (ROC). Therefore, we aimed to provide a bibliometric analysis of the evolving paradigms in the ROC treatment., Methods: Documents on ROC treatment were systematically collected from the MEDLINE database and Web of Science Core Collection (WOSCC). The retrieved documents were exported in the plain text file format, and files were named and saved to the paths specified by the Java application. Microsoft Excel (version 2010), Citespace (6.2.R4) and VOSviewer (1.6.19) were used for data analysis, and included the following: 1) annual publication trend; 2) contributions of countries, institutions and authors; 3) co-citation of journals and references; and 4) co-occurrence of keywords., Results: A total of 914 documents published in the MEDLINE and 9,980 ones in WOSCC were retrieved. There has been an upward trend in the productivity of publications on ROC treatment on by years. The United States was the leading contributor in this field, and the University of Texas System stood out as the most productive institution. Giovanni Scambia and Maurie Markman were the research leaders in the field of ROC treatment. The journal Gynecologic Oncology had the highest citation frequency. The reference entitled with "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer" got highest centrality of 0.14 in the co-citation network. Keyword analysis revealed that the focus of current ROC treatment was on platinum-based anticancer drugs, paclitaxel, angiogenesis inhibitors (AIs), immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPis)., Conclusion: Scholars from a multitude of countries have been instrumental in the advancement of ROC treatment. The research hotspots and trend in the field of predominantly originated from leading international journals and specialized periodicals focused on gynecologic oncology. Maintenance therapy using AIs or (and) PARPis has emerged as a significant complement to platinum-based chemotherapy for patients with ROC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hao, Song, Li and Guo.)

Introduction: Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous., Methods: Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes., Results: Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E-02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E-02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E-02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E-02) was related to dendritic cells (DCs)., Conclusion: These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zuo, Hu, Hao, Li, Shi, Guo, Ma, Li, Liang, Zhang, Mao, Xu and Shi.)

Developing thermally activated delayed fluorescence (TADF) near-infrared (NIR) organic light-emitting diodes (OLEDs) based on nondoped emitting layers is intriguing yet challenging, limited by low exciton utilization and notorious concentration quenching. Herein, a facile strategy is proposed to address this issue by incorporating an internal host component onto a traditional donor (D)-acceptor (A)-type red TADF molecule. A proof-of-concept emitter with an internal host is accordingly developed as well as a control one without an internal host. In the case of their monomer states, both emitters exhibit similar emission spectra due to their identical D-A pairs. However, under nondoped conditions, significant improvement in exciton utilization and quenching-resistant features are observed for the molecule with the internal host. The corresponding nondoped OLED yielded a maximum external quantum efficiency of 2.4%, with NIR emission peaking at 765 nm, which was a nearly 10-fold improvement relative to the efficiency based on the control molecule without an internal host. To the best of our knowledge, this result is on par with those of state-of-the art nondoped NIR TADF OLEDs in a similar emission region. These results offer a feasible pathway for the design and development of high-efficiency NIR nondoped OLEDs.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS., (© 2024. The Author(s).)

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency. Further, Chol-HDO@LMNPs, Chol-HDO-loaded, cerebrovascular endothelial cell membrane with DSPE-PEG 2000 -levodopa modification (L-DOPA-CECm)-coated nanoparticles (NPs), were developed for the targeted treatment of PD by tail intravenous injection. CECm facilitated the blood-brain barrier (BBB) penetration of NPs, together with cholesterol escaped from reticuloendothelial system uptake, as well as L-DOPA was decarboxylated into dopamine which promoted the NPs toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that the nanodecoys improved the efficacy of HDO on PD mice. These findings provide insights into the development of biomimetic nanodecoys loading HDO for precise therapy of PD. STATEMENT OF SIGNIFICANCE: The accumulation of α-synuclein (α-syn) aggregates is a hallmark of PD. Our previous study designed a specific antisense oligonucleotide (ASO) targeting human SNCA, but the traumatic intracerebroventricular (ICV) is not conducive to clinical application. Here, we further optimize the ASO by creating a DNA/DNA double-stranded molecule with cholesterol-conjugated, named Chol-HDO (coDNA), and develop a DA-targeted biomimetic nanodecoy Chol-HDO@LMNPs by engineering cerebrovascular endothelial cells membranes (CECm) with DSPE-PEG 2000 and L-DOPA. The in vivo results demonstrated that tail vein injection of Chol-HDO@LMNPs could target DA neurons in the brain and ameliorate motor deficits in a PD mouse model. This investigation provides a promising peripheral delivery platform of L-DOPA-CECm nanodecoy loaded with a new Chol-HDO (coDNA) targeting DA neurons in PD therapy., Competing Interests: Declaration of Competing Interest The authors have declared that there is no conflict of interest., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The models used to describe the light response of electron transport rate in photosynthesis play a crucial role in determining two key parameters i.e., the maximum electron transport rate ( J max ) and the saturation light intensity ( I sat ). However, not all models accurately fit J - I curves, and determine the values of J max and I sat . Here, three models, namely the double exponential (DE) model, the non-rectangular hyperbolic (NRH) model, and a mechanistic model developed by one of the coauthors (Z-P Ye) and his coworkers (referred to as the mechanistic model), were compared in terms of their ability to fit J-I curves and estimate J max and I sat . Here, we apply these three models to a series of previously collected Chl a fluorescence data from seven photosynthetic organisms, grown under different conditions. Our results show that the mechanistic model performed well in describing the J-I curves, regardless of whether photoinhibition/dynamic down-regulation of photosystem II (PSII) occurs. Moreover, both J max and I sat estimated by this model are in very good agreement with the measured data. On the contrary, although the DE model simulates quite well the J-I curve for the species studied, it significantly overestimates both the J max of Amaranthus hypochondriacus and the I sat of Microcystis aeruginosa grown under NH 4 + -N supply. More importantly, the light intensity required to achieve the potential maximum of J ( J s ) estimated by this model exceeds the unexpected high value of 10 5 μmol photons m -2 s -1 for Triticum aestivum and A. hypochondriacus . The NRH model fails to characterize the J-I curves with dynamic down-regulation/photoinhibition for Abies alba , Oryza sativa and M. aeruginosa . In addition, this model also significantly overestimates the values of J max for T. aestivum at 21% O 2 and A. hypochondriacus grown under normal condition, and significantly underestimates the values of J max for M. aeruginosa grown under NO 3 - N supply. Our study provides evidence that the 'mechanistic model' is much more suitable than both the DE and NRH models in fitting the J-I curves and in estimating the photosynthetic parameters. This is a powerful tool for studying light harvesting properties and the dynamic down-regulation of PSII/photoinhibition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ye, An, Govindjee, Robakowski, Stirbet, Yang, Hao, Kang and Wang.)

Realizing efficient red/near-infrared (NIR) electroluminescence (EL) by precisely modulating molecular aggregations of thermally activated delayed fluorescence (TADF) emitters is an attractive pathway, yet the molecular designs are elusive. Here, a new approach is proposed to manage molecular aggregation via a mild-twist acceptor-donor-acceptor (A-D-A)-type molecular design. A proof-of-concept TADF molecule, QCN-PhSAC-QCN, is developed that furnishes a fast radiative rate and obvious aggregation-induced emission feature. Its emission bands can be facilely shifted from intrinsic yellow to the red/NIR region via fine-tuning doping levels and molecular aggregates while maintaining elegant photoluminescence quantum yields benefiting from suppressed exciton annihilation processes. As a result, a QCN-PhSAC-QCN-based organic light-emitting diode (OLED) exhibits a record-setting external quantum efficiency (EQE) of 39.1% at a doping ratio of 10 wt.%, peaking at 620 nm. Moreover, its nondoped NIR OLED affords a champion EQE of 14.3% at 711 nm and retains outstanding EQEs of 5.40% and 2.35% at current densities of 10 and 100 mA cm -2 , respectively, which are the highest values among all NIR-TADF OLEDs at similar density levels. This work validates the feasibility of such mild-twist A-D-A-type molecular design for precisely controlling molecular aggregation while maintaining high efficiency, thus providing a promising pathway for high-performance red/NIR TADF OLEDs., (© 2023 Wiley-VCH GmbH.)

Genome-wide association studies (GWAS) have identified multiple risk variants for Parkinson's disease (PD). Nevertheless, how the risk variants confer the risk of PD remains largely unknown. We conducted a proteome-wide association study (PWAS) and summary-data-based mendelian randomization (SMR) analysis by integrating PD GWAS with proteome and protein quantitative trait loci (pQTL) data from human brain, plasma and CSF. We also performed a large transcriptome-wide association study (TWAS) and Fine-mapping of causal gene sets (FOCUS), leveraging joint-tissue imputation (JTI) prediction models of 22 tissues to identify and prioritize putatively causal genes. We further conducted PWAS, SMR, TWAS, and FOCUS using a multi-trait analysis of GWAS (MTAG) to identify additional PD risk genes to boost statistical power. In this large-scale study, we identified 16 genes whose genetically regulated protein abundance levels were associated with Parkinson's disease risk. We undertook a large-scale analysis of PD and correlated traits, through TWAS and FOCUS studies, and discovered 26 casual genes related to PD that had not been reported in previous TWAS. 5 genes ( CD38 , GPNMB , RAB29 , TMEM175 , TTC19 ) showed significant associations with PD at both the proteome-wide and transcriptome-wide levels. Our study provides new insights into the etiology and underlying genetic architecture of PD.

Background: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic., Methods: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery., Results: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic., Limitation: The absence of data from the early days of the COVID-19 outbreak., Conclusions: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Patients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood., Objective: The aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci., Methods: We used the summary statistics from genome-wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed., Results: MiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function-related biological processes., Conclusions: We confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune-related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background: The purpose of this study was to investigate the predictive value of the 5-factor modified frailty index (mFI-5) for postoperative mortality, delirium and pneumonia in patients over 65 years of age undergoing elective lung cancer surgery., Methods: Data were collected from a single-center retrospective cohort study conducted in a general tertiary hospital from January 2017 to August 2019. In total, the study included 1372 elderly patients aged over 65 who underwent elective lung cancer surgery. They were divided into frail group (mFI-5, 2-5), prefrail group (mFI-5, 1) and robust group (mFI-5, 0) on the basis of mFI-5 classification. The primary outcome was postoperative 1-year all-cause mortality. Secondary outcomes were postoperative pneumonia and postoperative delirium., Results: Frailty group had the highest incidence of postoperative delirium (frailty 31.2% versus prefrailty 1.6% versus robust 1.5%, p < 0.001), postoperative pneumonia (frailty 23.5% versus prefrailty 7.2% versus robust 7.7%, p < 0.001), and postoperative 1-year mortality (frailty 7.0% versus prefrailty 2.2% versus robust 1.9%. p < 0.001). Frail patients have significantly longer length of hospitalization than those in the robust group and prefrail patients (p < 0.001). Multivariate analysis showed a clear link between frailty and increased risk of postoperative delirium (aOR 2.775, 95% CI 1.776-5.417, p < 0.001), postoperative pneumonia (aOR 3.291, 95% CI 2.169-4.993, p < 0.001) and postoperative 1-year mortality (aOR 3.364, 95% CI, 1.516-7.464, p = 0.003)., Conclusions: mFI-5 has potential clinical utility in predicting postoperative death, delirium and pneumonia incidence in elderly patients undergoing radical lung cancer surgery. Frailty screening of patients (mFI-5) may provide benefits in risk stratification, targeted intervention efforts, and assist physicians in clinical decision-making., (© 2023. Society of Surgical Oncology.)

Background: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine., Methods: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes., Results: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine., Conclusions: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Preoperative evaluation of frailty is limited to a few surgical procedures. However, the evaluation in Chinese elderly gastric cancer (GC) patients remains blank., Aim: To validate and estimate the prognostic value of the 11-index modified frailty index (mFI-11) for predicting postoperative anastomotic fistula, intensive care unit (ICU) admission, and long-term survival in elderly patients (over 65 years of age) undergoing radical GC., Methods: This study was a retrospective cohort study which included patients who underwent elective gastrectomy with D2 Lymph node dissection between April 1, 2017 and April 1, 2019. The primary outcome was 1-year all-cause mortality. The secondary outcomes were admission to ICU, anastomotic fistula, and 6-mo mortality. Patients were divided into two groups according to the optimal grouping cutoff of 0.27 points from previous studies: High risk of frailty marked as mFI-11 High and low risk of frailty marked as mFI-11 Low . Survival curves between the two groups were compared, and univariate and multivariate regression analyses were performed to explore the relationship between preoperative frailty and postoperative complications in elderly patients undergoing radical GC. The discrimination ability of the mFI-11, prognostic nutritional index, and tumor-node-metastasis pathological stage to identify adverse postoperative outcomes was assessed by calculating the area under the receiver operating characteristic (ROC) curve., Results: A total of 1003 patients were included, of which 13.86% (139/1003) were defined as having mFI-11 High and 86.14% (864/1003) as having mFI-11 Low . By comparing the incidence of postoperative complications in the two groups of patients, it was found that mFI-11 High patients had higher rates of 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality than the mFI-11 Low group (18.0% vs 8.9%, P = 0.001; 31.7% vs 14.7%, P < 0.001; 7.9% vs 2.8%, P < 0.001; and 12.2% vs 3.6%, P < 0.001). Multivariate analysis revealed mFI-11 as an independent predictive indicator for postoperative outcome [1-year postoperative mortality: Adjusted odds ratio (aOR) = 4.432, 95% confidence interval (95%CI): 2.599-6.343, P = 0.003; admission to ICU: aOR = 2.058, 95%CI: 1.188-3.563, P = 0.010; anastomotic fistula: aOR = 2.852, 95%CI: 1.357-5.994, P = 0.006; 6-mo mortality: aOR = 2.438, 95%CI: 1.075-5.484, P = 0.033]. mFI-11 showed better prognostic efficacy in predicting 1-year postoperative mortality [area under the ROC curve (AUROC): 0.731], admission to ICU (AUROC: 0.776), anastomotic fistula (AUROC: 0.877), and 6-mo mortality (AUROC: 0.759)., Conclusion: Frailty as measured by mFI-11 could provide prognostic information for 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality in patients over 65 years old undergoing radical GC., Competing Interests: Conflict-of-interest statement: All authors declare that there is no conflict of interest to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 ( P =0.021), Ann Arbor stage Ⅲ-Ⅳ ( P =0.003), high LDH level ( P =0.003), involvement of bone marrow ( P =0.014). Age of ≥80 ( P =0.001) and a high LDH level ( P =0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS ( P =0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

The frequency of drought will increase under further warming. The increase in atmospheric CO 2 concentration, along with more frequent drought, will affect crop growth. We examined the changes of cell structure, photosynthetic physiology, antioxidant enzymes, osmotic regulatory substances, and yield of foxtail millet ( Setaria ita-lica ) leaves under different CO 2 concentrations (ambient air CO 2 concentration and ambient atmospheric CO 2 concentration + 200 μmol·mol -1 ) and water treatment (soil moisture content maintained at 45%-55%, and 70%-80% of field capacity, representing mild drought and normal water condition, respectively). The results showed that elevated CO 2 concentration increased the number of starch grains, the area of single starch grains, and the total area of starch grains in the chloroplast of millet mesophyll cells. Under mild drought condition, elevated CO 2 concentration increased net photosynthetic rate of millet leaves at the booting stage by 37.9%, but did not affect water use efficiency at this stage. Elevated CO 2 concentration increased net photosynthetic rate and water use efficiency of millet leaves under mild drought condition at the filling stage by 15.0% and 44.2%, respectively. Under mild drought condition, elevated CO 2 concentration increased the content of peroxidase (POD) and soluble sugar in millet leaves at the booting stage by 39.3% and 8.0%, respectively, but decreased proline content by 31.5%. It increased the content of POD in millet leaves at the filling stage by 26.5% but decreased the content of MDA and proline by 37.2% and 39.3%, respectively. Under mild drought condition, elevated CO 2 concentration significantly increased the number of grain spikes by 44.7% and yield by 52.3% in both years compared with normal water condition. The effect of elevated CO 2 concentration on grain yield under mild drought conditions was higher than that under normal water condition. Under mild drought conditions, elevated CO 2 concentration increased leaf thickness, vascular bundle sheath cross-sectional area, net photosynthetic rate, and water use efficiency of millet, improved the antioxidant oxidase activity, and changed the concentration of osmotic regulatory substances, alleviated the nega-tive effect of drought on foxtail millet, and finally increased the number of grains per ear and yield of foxtail millet. This study would provide a theoretical basis for millet production and sustainable agricultural development in arid areas under future climate change.

Background: Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy characterized by massive fibrosis and has ineffective adjuvant therapies. Here, we demonstrate the potential of angiotensin receptor blockers (ARBs) in targeting iCCA., Methods: Masson's trichrome staining was used to assess the effect of ARBs in iCCA specimens, CCK8 and gel contraction assays in vitro and in xenograft models in vivo. RNA-seq and ATAC-seq were used for mechanistic investigations., Results: Patients with iCCA who were administered ARBs had a better prognosis and a lower proportion of tumour stroma, indicating alleviated fibrosis. The presence of AGTR1, the ARBs receptor, is associated with a poor prognosis of iCCA and is highly expressed in tumour tissues and cancer-associated fibroblasts (CAFs). The ARBs strongly attenuated the viability of AGTR1+ CAFs in vitro and retarded tumour progression and fibrosis in xenograft models of co-cultured CAFs and iCCA cells. Still, they did not have a significant effect on AGTR1- CAFs. Moreover, ARBs decreased the secretion of AGTR1+ CAF-derived MFAP5 via the Hippo pathway, weakened the interaction between CAFs and iCCA cells, and impaired the aggressiveness of iCCA cells by attenuating the activation of the Notch1 pathway in iCCA cells., Conclusions: ARBs exhibit anti-fibrotic function by inhibiting the viability of AGTR1+ CAFs. These findings support using ARBs as a novel therapeutic option for targeting iCCA., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Objective: To determine whether intraoperative transfusion of allogeneic or autologous blood is associated with an increased incidence of postoperative delirium (POD) after total knee arthroplasty (TKA) and total hip arthroplasty (THA)., Methods: The medical records of 1,143 older (≥65 years old) patients who received an intraoperative blood transfusion while undergoing total knee or hip arthroplasty at the First Medical Center of Chinese PLA General Hospital from 2014 to 2019 were reviewed; of these patients, 742 (64.92%) received allogeneic blood, while 401 (35.08%) received autologous blood. Patients who received autologous transfusion were paired with those received allogeneic transfusion using 1:1 propensity score matching method. The primary outcome was POD. The secondary outcomes were postoperative complications, including heart failure, deep vein thrombosis, myocardial infarction, stroke, and lung infection. Multivariable nominal logistic regression was used to identify any independent associations between intraoperative blood transfusions and POD, and secondary postoperative complications, respectively., Results: Postoperative delirium occurred in 6.6% (49/742) of patients who had received an allogeneic blood transfusion and in 2.0% (8/401) of patients who had received an autologous blood transfusion. It is noteworthy that the multivariable logistic regression demonstrated a significant association between intraoperative allogeneic blood transfusion and POD (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.95-9.77; p  < 0.001). After PSM, Allogeneic transfusion was also the strongest predictor for POD (OR: 4.43; 95% CI: 2.09-10.58; p  < 0.001)., Conclusions: In the patients who had received THA or TKA, intraoperative allogeneic blood transfusions were associated with an increased risk of POD., 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., (© 2023 OuYang, Hao, Yu, Lou, Cao, Yu and Mi.)

Background: Lacunar stroke accounts for a quarter of all strokes, but little is known about the underlying pathological mechanisms. Analysis of serum metabolites may allow better understanding of the underlying biological processes. Mendelian randomization (MR) can provide information on the causality of associations., Aims: To identify causal relationships between serum metabolites and lacunar stroke., Methods: We applied a two-sample MR analysis to evaluate relationships between 486 serum metabolites and lacunar stroke. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of the exposure on the outcome, while sensitivity analyses were performed using MR-Egger, weighted median, and MR-PRESSO to eliminate the pleiotropy. We also performed a metabolic pathway analysis to identify potential metabolic pathways., Results: We identified 15 known (8 risk and 7 protective) and 14 unknown serum metabolites associated with lacunar stroke. Among the known risk metabolites, two were lipids (1-linoleoylglycerophosphoethanolamine and dihomo-linolenate (20:3n3 or n6)), five amino acids (kynurenine, isobutyrylcarnitine, aspartate, trans-4-hydroxyproline, and 3-methyl-2-oxovalerate), and one peptide (ADSGEGDFXAEGGGVR). The known protective metabolites included four lipids (4-androsten-3beta,17beta-diol disulfate 1, 1-palmitoleoylglycerophosphocholine, adrenate (22:4n6), and glycodeoxycholate), one amino acid (methionine), and two exogenous metabolites (homostachydrine and 2-methoxyacetaminophen sulfate). Metabolic pathway analysis identified several pathways that might be involved in the disease., Conclusion: We identified eight risk and seven protective human serum metabolites associated with lacunar stroke. Isobutyrylcarnitine was positively associated with an increased risk of lacunar stroke. In addition, 3-methyl-2-oxovalerate and aspartate may be involved in the disease pathogenesis through metabolic pathways.

Background: Isolated aortic brachiocephalic artery (IABA) is a rare congenital aortic arch anomaly. It is difficult to diagnose IABA prenatally and the prevalence in the prenatal population is unknown., Purpose: To evaluate the echocardiographic characteristics and associations in fetuses with IABA., Material and Methods: We retrospectively analyzed all cases of prenatal diagnosis of IABA from January 2012 to November 2020 and reviewed the follow-up results. Copy Number Variation Sequencing (CNV-Seq) was performed using the biological specimens of the of the fetuses and family members., Results: Ten cases (10/45652, 0.022%) of IABA were identified in our center. The prevalence of the cases with isolated left subclavian artery (ILSCA) in the right aortic arch (RAA) population was 0.98% (6/613). The ILSCA was the most common isolated arch branch. All the isolated branches were on the opposite side of aortic arch in all the cases. The "ice stick" sign in the coronal section could be seen in most cases of IABA. Of the 10 cases, 8 (8/10, 80%) were associated with tetralogy of Fallot (TOF). Two cases of IABA were combined with 22q11.2 deletion syndrome., Conclusion: IABA is a rare aortic anomaly. ILSCA was the most common isolated arch branch and TOF was the most common associated intra-cardiac anomaly. The "ice stick" sign in the coronal section could indicate a diagnosis of the IABA.

Extracellular vesicles (EVs) have emerged as promising candidates for multiple biomedical applications. Major types of EVs include exosomes, microvesicles, and apoptotic bodies (ABs). ABs are conferred most properties from parent cells in the final stages of apoptosis. A wide variety of sources and stable morphological features are endowed to ABs by the rigorous apoptotic program. ABs accommodate more functional biomolecules by relying on the larger volume and maintaining their naturalness in circulation. The predominant body surface ratio of ABs facilitates their recognition by recipient cells and is advantageous for interactions with microenvironments. ABs can modulate and alleviate symptoms of numerous diseases for their origins, circulation, and high biocompatibility. In addition, ABs have been emerging in disease diagnosis, immunotherapy, regenerative therapy, and drug delivery. Here, we aim to present a thorough discussion on current knowledge about ABs. Of particular interest, we will summarize the application of AB-based strategies for diagnosis and disease therapy. Perspectives for the development of ABs in biomedical applications are highlighted., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks., Methods: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency as those in the superficial acupuncture (SA) group-defined as a type of sham control by avoiding deqi sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs)., Results: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n = 110) vs 48.1% in the SA group (n = 108) at week 16 (OR, 2.65; 95% CI, 1.5 to 4.77; p < 0.001); and it was 68.2% in the TA group vs 50% in the SA group at week 32 (OR, 2.4; 95%CI, 1.36 to 4.3; p < 0.001). The reduction in MHDs was 13.1 ± 9.8 days in the TA group vs 8.8 ± 9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p < 0.001), and the reduction was 14 ± 10.5 days in the TA group vs 9.5 ± 9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p < 0.001). Four mild adverse events were reported; 3 in the TA group vs 1in the SA group., Discussion: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment., Trial Registration Information: ClinicalTrials.gov: NCT03133884 (clinicaltrials.gov/ct2/show/NCT03133884)., Classification of Evidence: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces the mean headache days (per month) in patients with CTTH., (© 2022 American Academy of Neurology.)

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery., (© 2022. The Author(s).)

Nymphalidae is the most diverse butterfly family worldwide, with more than 6000 species, whereas the mitogenomic data of nymphalid species, especially the subfamily Danainae, is still lacking for more comprehensive systematic studies. To this contribution, the complete mitogenome of Danaus genutia (Lepidoptera: Nymphalidae: Danainae) was determined via sequencing and annotating. The mitogenome in total consists of 15,255 base pairs (bp), containing 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and a 440-bp noncoding A+T-rich region. Furthermore, phylogeny of the subfamily Danainae was reconstructed applying maximum likelihood and Bayesian inference on the basis of the mitogenomic data sets. Combined with our analysis and previous studies, the genus-level phylogenetic relationships within the subfamily Danainae are ((Tirumala + Danaus) + ((Idea + Euploea) + (Ideopsis + Parantica))). This study offers molecular information and provides a new perspective for phylogenetic research within the subfamily Danainae., (© 2022 Wiley Periodicals LLC.)

Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R 2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.

A Gram-positive strain APA H-16(1) T was isolated from a saline-alkali soil sample collected from Heilongjiang Province, China. Cells were rod shaped, non-motile, endospore forming, and aerobic. Growth occurred at 10-45 °C (optimum, 35 °C), pH 7.0-10.5 (optimum, pH 9.5), and could tolerate NaCl up to 15.0% (w/v). Strain showed low 16S rRNA gene sequence similarities with Alteribacter natronophilus (97.8%), Alteribacter aurantiacus (97.7%), and Alteribacter populi (97.1%). The cell wall peptidoglycan was meso-diaminopimelic acid. The predominant menaquinone was MK-7. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified aminophospholipids, unidentified phospholipid, and unidentified lipid. The major fatty acids were anteiso-C 15:0 , and iso-C 15:0 . The genomic G + C content was 45.1%. The average nucleotide identity and digital DNA-DNA hybridization values between strain APA H-16(1) T and the most closely related species were below the cut-off level (95-96%; 70%) for species delineation. Based on phenotypic, phylogenetic, chemotaxonomic, and genome comparison, strain APA H-16(1) T represents a novel species of the genus Alteribacter, for which the name Alteribacter salitolerans sp. nov. is proposed. The type strain is APA H-16(1) T (= KCTC 43228 T  = CICC 25092 T )., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mechanisms underlying leaf photosynthetic acclimation in winter wheat under elevation of CO 2 concentration ([CO 2 ]) remain unclear. The aim of the study was to investigate the effects of source-sink variation on photosynthetic acclimation induced by drought under elevated [CO 2 ]. A winter wheat ( Triticum aestivum L. 'Zhengmai 9023') pot experiment was conducted in open top climate chambers with [CO 2 ] of 400μmol·mol -1 or 600 μmol·mol -1 and soil water content at 80%±5% or 55%±5% of field capacity. The parameters of chlorophyll fluorescence, electron transport rate, photosynthetic curve, leaf nitrogen content, and grain yield were measured at the elongation and heading stages. Under drought condition, leaf PSⅡ photochemical efficiency was not affected by elevated [CO 2 ], but the maximum electron transport rate and the ratio of electron partitioned to carboxylation reaction in Calvin cycle was increased at the elongation stage, and thus the Rubisco carboxylation rate and maximum photosynthetic rate were increased. Although the maximum electron transportation rate and partitioning ratio of electron to carboxylation reaction in Calvin cycle remained high at the heading stage, the PSⅡ photochemical efficiency, Rubisco carboxylation rate, and triose phosphate utilization rate were decreased by elevated [CO 2 ], which consequently reduced the maximum photosynthetic rate for plant under drought stress. Under drought condition, elevated [CO 2 ] increased wheat tiller biomass, kernel number, and kernel weight per ear, but decreased infertile kernel number, resulting in an overall increase in grain weight. In conclusion, the elevated [CO 2 ]-induced increase in wheat grain yield per tiller under drought condition was mainly caused by enhanced photosynthetic performance at the elongation stage. The photosynthetic acclimation in source leaves during the heading stage under elevated [CO 2 ] was mainly attributed to the reduction in PSⅡ photochemical efficiency and triose phosphate utilization rate, but not to the maximum electron transportation rate, ratio of electron partitioned to carboxylation in Calvin cycle or sink leaf strength.

Objective: To investigate the changes of occlusal delay time, percentage of occlusal force and patients' subjective satisfaction of masticatory function for single implant crown in one year after the application of space reserved occlusion design. To provide data support and suggestions for clinical occlusion design. Methods: Patients who had received single posterior dental implant restoration in Department of Prosthodontics, Capital Medical University School of Stomatology from January 2019 to December 2019 were selected. At 0.5, 3, 6 and 12 months after restoration, the T-scan Ⅲ occlusal analyzer was used to detect and record the initial occlusal contact time of the natural tooth and implanted single crown, the occlusal force percentage of single implant prosthesis and corresponding tooth on the contralateral side (control teeth) on the contralateral side (control teeth) were also recorded. Subjective satisfaction with the masticatory function of the implants was recorded using visual analogue scale (VAS). The changes of occlusal delay time (the difference of the initial occlusal time between implant restoration and the natural teeth), percentage of occlusal force and patients' subjective feeling with time were analyzed. All data were analyzed by repeated measurement analysis of variance, bilatteral P <0.01 was considered statistically significant. Results: A total of 48 patients aged (36.8±8.4) years (23 males, 25 females, aged 23-50 years) were recruited. The occlusal delay time at 0.5 months was 0.15 (0.08, 0.20) s, at 3 months was 0.11 (0.06, 0.16) s, at 6 months was 0.07 (0.03, 0.13) s and at 12 months was 0.06 (0.03, 0.10) s. The occlusal delay time was shortened at every two time points, and the occlusal force percentage of the implant crown increased significantly. The percentage of occlusal force of implant prosthesis at 0.5 months was (7.7±4.8)%, at 3 months was (10.6±5.9)%, at 6 months was (12.3±6.2)% and at 12 months was (13.2±6.7)%. The most significant change was during the period of 0.5-3 months. At 0.5 months, the occlusal force of implant prosthesis was significantly lower than that of control teeth (14.3±6.5)% ( P <0.01). The VAS score at 0.5 months was (7.06±1.64) and was (8.71±0.74) at 12 months. The score was increased and the difference was statistically significant from 3 month to 12 month ( P <0.01). Conclusions: The change of occlusal force percentage of single posterior dental implant is most obvious within 3 months after restoration. The occlusal condition should be reexamined and adjust occlusal after 3 months of implant restoration as appropriate.

Inflammation as a host's excessive immune response to stimulation, is involved in the development of numerous diseases. To discover novel anti-inflammatory agents and based on our previous synthetic work on marine natural product Chrysamide B, it and a series of derivatives were synthesized and evaluated for their anti-inflammatory activity on inhibition of LPS-induced NO production. Then the preliminary structure-activity relationships were conducted. Among them, Chrysamide B is the most potent anti-inflammatory agent with low cytotoxicity and strong inhibition on the production of NO (IC 50  = 0.010 μM) and the activity of iNOS (IC 50  = 0.082 μM) in LPS-stimulated RAW 264.7 cells. Primary studies suggested that the mechanism of action may be that it interfered the formation of active dimeric iNOS but not affected transcription and translation. Furthermore, its good performance of anti-inflammatory effect on LPS-induced multiple inflammatory cytokines production, carrageenan-induced paw edema, and endotoxin-induced septic mice, was observed. We believe that these findings would provide an idea for the further modification and research of these analogs in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To prepare a chitosan-modified cationic nanoemulsion that could be used to prolong the residence time of nasal vaccines in the nasal cavity and improve the cellular uptake efficiency so as to enhance the immune efficacy of nasal vaccines., Methods: A nanoemulsion-based vaccine coated with chitosan was prepared, and the particle size, potential, antigen encapsulation efficiency, stability as well as cytotoxicity were examined. The uptake efficiency of vaccine on different cells and the residence time of vaccine in the nasal cavity were measured. Finally, nasal vaccine was administered on mice and the antibody levels in the serum and in the nasal lavage fluids of the immunized mice were examined., Results: The nanoemulsion-based vaccine had an average particle size of (167.2±0.75) nm, a polydispersity index (PDI) of 0.21±0.01, and an average potential of (13.7±0.85) mV. The encapsulation efficiency of antigen was 92.7%. The nanoemulsion-based vaccine had good stability and did not show obvious cytotoxicity in Madin-Darby canine kidney (MDCK) epithelial cells. The vaccine demonstrated relatively high cellular uptake of antigens on DC2.4 and MDCK cells at (49.7±3.45)% and (59.7±2.19)%, respectively. Besides, the cationic nanoemulsion also significantly increased the residence time of the antigen, and a considerable amount of nanoemulsion-based vaccine was found remaining in the nasal cavity 60 minutes after administration. Compared with free antigen and the nanoemulsion without chitosan modification, the chitosan-modified nanoemulsion vaccine induced higher systemic and mucosal antibody levels in mice after nasal immunization ( P <0.01)., Conclusion: The chitosan-modified nanoemulsion vaccine prepared in the study can enhance the immune efficacy of nasal vaccines, showing great potential to be used as a delivery carrier for nasal vaccines., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

In sheep industry, hypothermia caused by insufficient brown adipose tissue (BAT) deposits is one of the major causes of lamb deaths. Enhancing the formation and function of BAT in neonatal lamb increases thermogenesis and hence reduces economic losses. The aim of the present study was to explore the effect and mechanism of melatonin on sheep brown adipocyte formation and function. Sheep brown adipocyte precursor cells (SBACs) isolated from perirenal BAT were treated with melatonin (1 and 10 nM). The SBACs subjected to melatonin exhibited a decreased proliferation ability, accompanied by down-regulated proliferating cell nuclear antigen, cyclin D1, and CDK4 protein contents in a melatonin dose-dependent manner. Melatonin promoted brown adipocyte formation and induced the expression of brown adipogenic markers, including uncoupling protein 1 and PR domain-containing 16 during differentiation of SBAC. Moreover, the AMP-activated protein kinase α1 (AMPKα1) activity was positively correlated with brown adipocyte formation potential. Importantly, melatonin effectively activated AMPKα1. Furthermore, promotional effects of melatonin were abolished by AMPKα1 knockout, suggesting the involvement of AMPKα1 in this process. Collectively, these results suggested that melatonin enhanced brown adipocyte formation in SBACs in vitro through activation of AMPKα1., 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 © 2021 Gao, Deng, Li, Wang, Zhang, Hao and Zhao.)

An alkaliphilic actinobacterial strain, designated Hz 6-5 T , was isolated from saline-alkaline soil from Songnen Plain in north-eastern China. The isolate formed light yellow-colored colonies and its cells were Gram-staining positive, non-motile, and non-spore-forming short rods. The strain was aerobic with optimal growth at 33 °C, pH 9.0, and in the presence of 0.5% (w/v) NaCl or 3% (w/v) KCl. It was catalase-positive and oxidase-negative. The isolate had highest 16S rRNA gene sequence similarities to the type strains of the species Nesternkonia natronophila M8 T (98.2%), N. salmonea GY074 T (98.1%), and N. sphaerica GY239 T (97.4%), and the isolate formed a subclade with the type strains of these species in the neighbor-joining tree based on the 16S rRNA gene sequences. The phylogenetic tree based on the phylogenomic analysis also showed the same results. The DNA‒DNA relatedness (DDH) values of isolate Hz 6-5 T with N. natronophila M8 T , N. halophila DSM 16378 T , and N. halobia CGMCC 1.2323 T were 21.2%, 36.5%, and 32.0%, respectively. The characteristic diamino acid of strain Hz 6-5 T was found to be lysine. The respiratory quinones were MK-9, MK-8, MK-7(H 4 ), MK-7(H 2 ) and MK-7 and the major cellular fatty acids (> 10%) were anteiso-C 15:0 , anteiso-C 17:0 and iso-C 16:0 . The polar lipids detected for strain Hz 6-5 T were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, an unidentified glycolipid, and two unidentified phospholipids. The DNA G + C content of isolate Hz 6-5 T was 60.8%. Based on the results of phylogenetic analysis supported by morphological, physiological, chemotaxonomic, and other differentiating phenotypic evidence, strain Hz 6-5 T is considered to represent a novel species of the genus Nesterenkonia, for which the name Nesterenkonia haasae sp. nov. is proposed. The type strain is Hz 6-5 T (=CPCC 205100 T =NBRC 113521 T ).

Purpose: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data., Methods: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model., Results: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P<0.05). Stratified analysis results further confirmed this model performed well. By analyzing the validation group, the results of receiver operating characteristic (ROC) curve analysis and survival analysis further validated this model., Conclusion: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC., (© 2021 The Author(s).)

Some grain processing by-products rich in digestible fiber are good feed resources for ruminants. This experiment was conducted to investigate the effects of replacing a portion of corn and corn stover with the combinations of corn bran and soybean hulls in the diet of fattening lambs on nutrient digestion, rumen microbial protein synthesis, and growth performance. A total of 36 Dorper × Small Thin-Tailed crossbred ram lambs (BW = 22.2 ± 0.92 kg; mean ± SD) were randomly divided into three groups, and each group was fed 1 of 3 treatment diets: 1) 0% corn bran and soybean hulls (control); 2) 9% corn bran and 9% soybean hulls (18MIX); and 3) 17% corn bran and 17% soybean hulls (34MIX). The feeding experiment was conducted for 70 days, with the first 10 days for adaption. The DM intake was higher for 34MIX (1635.3 g/d) than for control diet (1434.7 g/d; P = 0.001). Lambs fed 18MIX and 34MIX diets (230.2 and 263.6 g/d, respectively) had higher average daily gain and feed efficiency than those fed control diet (194.8 g/d; P < 0.01). Dry matter and NDF digestibility for 34MIX group (60.9 and 49.5%) were higher than for control (55.2 and 41.3%; P < 0.01). No difference was observed in nitrogen digestibility among treatment diets (P = 0.778). The lambs fed 34MIX diet excreted more urinary purine derivatives, indicating that more microbial protein was yielded than those fed control diet (P < 0.01), while 18MIX was not different from the other two diets (P > 0.05). The metabolizable protein supplies were improved with increasing co-products inclusion rate. The results indicated that corn bran and soybean hulls in combination can effectively replace a portion of corn and corn stover in the ration of finishing lambs with positive effect on nutrient digestion and growth performance., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Preliminary study of magnetic resonance (MR) diffusion kurtosis imaging (DKI) assessing the pathological glial fibrillary acidic protein (GFAP), TopoIIα, and O 6-methylguanine-DNA methyltransferase (MGMT) expression in astrocytomas., Materials and Methods: This study was approved by the local ethics committee, and informed consent was obtained from all participants. Sixty-six cases with pathologically proven astrocytomas were enrolled in this study; of which, 34 were high grade and remaining 32 were low grade. They patients underwent conventional MRI head scan, DKI scan, and enhanced scan under the same conditions. Fractional anisotropy (FA) and mean kurtosis (MK) calculated from DKI, as well as GFAP, TopoIIα, and MGMT expression level were compared prospectively between high and low-grade astrocytomas. Spearman rank correlation analysis was used for comparing values of DKI and GFAP, TopoIIα, and MGMT expression level in the two groups., Results: The MK values were significantly higher in high-grade astrocytomas than those in low-grade astrocytomas (P < 0.05); FA values demonstrated no significant difference between the two groups (P = 0.331). GFAP expression level was significantly lower in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). Topo-IIα expression level were significantly higher in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). There was no significant difference in MGMT expression level between the two groups (P = 0.679). MK values were negatively correlated with the expression of GFAP (r = -0.836; P = 0.03), however, they were positively correlated with the expression of Topo-IIα (r = 0.896; P = 0.01). FA values were not correlated with the expression of GFAP (r = 0.366; P = 0.05), Topo-IIα (r = -0.562; P = 0.05), and MGMT (r = -0.153; P = 0.10)., Conclusion: MK, the DKI parameter values of astrocytomas, was significantly correlated to the expression of GFAP and TopoIIα. To a certain extent, applying DKI may provide the biological behavior of tumor cell differentiation, proliferation activity, invasion and metastasis, and can guide individual treatment., Competing Interests: None

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The climate change caused by elevated CO 2 concentration and drought are bound to affect the growth of soybean. Few studies have addressed the effects of elevated CO 2 concentration on the physiology and biochemistry of soybean under drought stress. Here, we examined the changes of photosynthetic ability, photosynthetic pigment accumulation, antioxidant level, osmotic adjustment substances, hormone levels, signal transduction enzymes and gene expression level of soybean at flowering stage under different CO 2 concentration (400 and 600 μmol·mol -1 ) and drought stress (normal water: leaf relative water content was 83%-90%; drought stress: leaf relative water content was 64%-70%). The results showed that the transpiration rate, water use efficiency and net photosynthetic rate of soybean leaves were significantly increased by elevated CO 2 concentration, but the content of chlorophyll b was decreased under drought stress. Elevated CO 2 concentration significantly increased peroxidase activity and abscisic acid content of leaves under drought stress, decreased the content of proline, and did not affect the content of soluble saccharides. The increased CO 2 concentration under drought stress significantly promoted the content of calcium-dependent protein kinase and glutathione-S-transferase, and up-regulated the expression of related genes, while significantly decreased the content of mitogen-activated protein kinase and the heat shock protein, and down-regulated the expression of their genes. The results would be helpful to understand the impacts of climate change on the growth, physiology and biochemistry of soybean, and to deal with the production problems of soybean under future climate change.

In recent decades, with the rapid development of dental implant technology, dental implants have been widely used in clinical practice. Various complications, including a lack of osseointegration, may occur after dental implantation. However, the occurrence of osteointegration failure after dental implantation is often complicated and unpredictable, and existing treatment methods cannot reverse osteointegration failure to achieve the optimum condition. A noninvasive, easy-to-operate, low-cost, fast-acting mechanotherapy is expected to solve this problem. Extracorporeal shock wave therapy (ESWT) is widely used to treat delayed healing, bone nonunion fractures, femoral head necrosis and other orthopedic diseases and plays a significant role in promoting bone regeneration. Studies have shown that ESWT can promote bone formation and osseointegration of titanium devices in vivo. In previous experiments, ESWT was found to regulate the activity of inflammatory cells, osteoblasts and mesenchymal stem cells. Studies have also mentioned the role of ESWT in promoting angiogenesis and bactericidal activity. Therefore, our hypothesis is that extracorporeal shock wave therapy can facilitate the realization of osteointegration by regulating the immune response, inducing regeneration of the jaw and alveolar bone, and promoting angiogenesis and bactericidal efficacy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)