Publications by authors named "Ben-Quan Shen"

156,307 Publications

The role of family communication patterns in intergenerational COVID-19 discussions and preventive behaviors: a social cognitive approach.

Authors:
Wanqi Gong Li Crystal Jiang Qin Guo Fei Shen

BMC Psychol 2023 Sep 26;11(1):290. Epub 2023 Sep 26.

Department of Media and Communication, City University of Hong Kong, Hong Kong, 999077, China.

Background: This study explores and compares the influences of family communication patterns (conversation orientation and conformity orientation) on family discussion and preventive behaviors for older parents and their adult children in the context of the early COVID-19 outbreak.

Methods: A total of 248 participants, including 117 parents and 131 adult children, participated in an online survey in February 2020. Participants reported family communication patterns, family discussions related to COVID-19, and their preventive behaviors.

Results: Conversation orientation was positively associated with information sharing and scientific discussion for older parents and adult children. Our results revealed the differential influences of conformity orientation on older parents and adult children. Conformity orientation was positively associated with scientific discussion for older parents but was not significantly associated with any form of family discussion reported by adult children. There was a significant interaction effect of conversation orientation and conformity orientation on disputed communication within the family, suggesting that conflicts may arise in COVID-related discussions when parents and adult children value conversation and conformity. Scientific discussion was found to mediate the relationships between family communication patterns and preventive behaviors. The effects of scientific discussions were stronger for older parents than for adult children.

Conclusions: Family communication patterns can be associated with preventive behaviors through different forms of family discussion about COVID-19. Conversation orientation is a strong facilitator for positive behavioral effects and scientific discussion is the most benign form of family health discussion. Health communication efforts should enhance the agency role of the family and motivate scientific discussion in health practices.
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http://dx.doi.org/10.1186/s40359-023-01331-yDOI Listing
September 2023

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy.

Authors:
Kunlu Shen Mengyuan Zhang Ruiheng Zhao Yun Li Chunxiao Li Xin Hou Bingqing Sun Bowen Liu Min Xiang Jiangtao Lin

Respir Res 2023 Sep 26;24(1):231. Epub 2023 Sep 26.

National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Chinese Academy of Medical Sciences, Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, 100029, Beijing, China.

Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.
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http://dx.doi.org/10.1186/s12931-023-02504-4DOI Listing
September 2023

Air pollution exposure and plasma fatty acid profile in pregnant women: a cohort study.

Authors:
Chenhui Yang Ye Shen Yiqiong Zhang Han Xiao Xiaojie Sun Jiaqiang Liao Xinmei Chen Wenxin Zhang Ling Yu Wei Xia Shunqing Xu Yuanyuan Li

Environ Sci Pollut Res Int 2023 Sep 26. Epub 2023 Sep 26.

Institute of Maternal and Child Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China.

Air pollution exposure was known to result in body impairments by inducing inflammation and oxidation. But little is known about the associations of air pollutants with plasma fatty acid profile which may play important roles in the impairment of air pollutants based on the related mechanism, especially in pregnant women. This study aimed to explore the relationships of air pollution exposure with plasma fatty acid profile and the potential effect modification by pre-pregnancy body mass index (BMI). Based on a cohort in Wuhan, China, we measured concentrations of plasma fatty acids of 519 pregnant women enrolled from 2013 to 2016 by gas chromatography-mass spectrometry (GC-MS). Levels of exposure to air pollutants (fine particulate matter (PM), inhalable particles (PM), nitrogen dioxide (NO), sulfur dioxide (SO), and carbon monoxide (CO)) were estimated by using spatial-temporal land use regression models and calculated in three periods (average concentrations during 1 day, 1 week, and 1 month before the phlebotomizing day in the first trimester). Per interquartile range increment of the levels of air pollution exposure 1 day before phlebotomizing was related to 1.21-2.01% increment of omega-6 polyunsaturated fatty acids (n-6PUFA) and 0.63-1.74% decrement of omega-3 polyunsaturated fatty acids (n-3PUFA). Besides, relationships above were kept robust in the analysis during 1 week and 1 month before phlebotomizing. In women with normal BMI, plasma fatty acid profile was observed to be more sensitive to air pollutants. Our study demonstrated that increment of exposure to air pollutants was associated with higher plasma n-6PUFA known to be pro-inflammatory and lower plasma n-3PUFA known to be anti-inflammatory, which was more sensitive in pregnant women with normal BMI. Our findings suggested that changes in plasma fatty acid profile should cause concerns and may serve as biomarkers in the further studies. Future studies are needed to validate our findings and elucidate the underlying mechanisms.
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http://dx.doi.org/10.1007/s11356-023-29886-8DOI Listing
September 2023

Disentangling in-vivo microstructural changes of white and gray matter in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

Authors:
Shuchang Zhong Jingjing Lou Ke Ma Zhenyu Shu Lin Chen Chao Li Qing Ye Liang Zhou Ye Shen Xiangming Ye Jie Zhang

Brain Imaging Behav 2023 Sep 27. Epub 2023 Sep 27.

Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.

The microstructural characteristics of white and gray matter in mild cognitive impairment (MCI) and the early-stage of Alzheimer's disease (AD) remain unclear. This study aimed to systematically identify the microstructural damages of MCI/AD in studies using neurite orientation dispersion and density imaging (NODDI), and explore their correlations with cognitive performance. Multiple databases were searched for eligible studies. The 10 eligible NODDI studies were finally included. Patients with MCI/AD showed overall significant reductions in neurite density index (NDI) of specific white matter structures in bilateral hemispheres (left hemisphere: -0.40 [-0.53, -0.27], P < 0.001; right: -0.33 [-0.47, -0.19], P < 0.001), involving the bilateral superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), the left posterior thalamic radiation (PTR), and the left cingulum. White matter regions exhibited significant increased orientation dispersion index (ODI) (left: 0.25 [0.02, 0.48], P < 0.05; right: 0.27 [0.07, 0.46], P < 0.05), including the left cingulum, the right UF, and the bilateral parahippocampal cingulum (PHC), and PTR. Additionally, the ODI of gray matter showed significant reduction in bilateral hippocampi (left: -0.97 [-1.42, -0.51], P < 0.001; right: -0.90 [-1.35, -0.45], P < 0.001). The cognitive performance in MCI/AD was significantly associated with NDI (r = 0.50, P < 0.001). Our findings highlight the microstructural changes in MCI/AD were characterized by decreased fiber orientation dispersion in the hippocampus, and decreased neurite density and increased fiber orientation dispersion in specific white matter tracts, including the cingulum, UF, and PTR. Moreover, the decreased NDI may indicate the declined cognitive level of MCI/AD patients.
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http://dx.doi.org/10.1007/s11682-023-00805-2DOI Listing
September 2023

Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis.

Authors:
Jianfan Chen Xueqing Xu Song Chen Ting Lu Yingchun Zheng Zhongzhi Gan Zongrui Shen Shunfei Ma Duocai Wang Leyi Su Fei He Xuan Shang Huiyong Xu Dong Chen Leitao Zhang Fu Xiong

Int J Oral Sci 2023 Sep 26;15(1):46. Epub 2023 Sep 26.

Department of Medical Genetics, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
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http://dx.doi.org/10.1038/s41368-023-00244-1DOI Listing
September 2023

Lapachol inhibits the growth of lung cancer by reversing M2-like macrophage polarization via activating NF-κB signaling pathway.

Authors:
Zhengzheng Zhang Luyao Bai Chunhua Lu Xintong Li Yang Wu Xiaochun Zhang Yuemao Shen

Cell Signal 2023 Sep 24:110902. Epub 2023 Sep 24.

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:

Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment (TME) and improve innate and adaptive antitumor immunity. Lapachol, a naturally occurring 1,4-naphthoquinone, exhibits various pharmacological activities including antitumor, anti-leishmanial, antimalarial and antiseptic. In this study, we investigated the relevance of macrophage polarization and the antitumor effect of lapachol in Lewis lung cancer (LLC) both in vitro and in vivo. This study demonstrated that lapachol significantly reversed the polarization of M2-like macrophages thus that were endowed with the ability to kill LLC cells by activating NF-κB signaling pathway. Furthermore, lapachol effectively suppressed tumor growth in C57BL/6 mice bearing lung tumors by reducing the proportion of M2-like macrophages. Overall, our findings clearly illustrated that lapachol could reverse the polarization of M2-like macrophages to improve the immunosuppressive tumor microenvironment, and had the potential to be developed as an immunomodulatory antitumor agent.
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http://dx.doi.org/10.1016/j.cellsig.2023.110902DOI Listing
September 2023

Racial and Ethnic Differences in Long-Term Adverse Radiotherapy Effects among Breast Cancer Survivors.

Authors:
Kevin Diao Xiudong Lei Weiguo He Reshma Jagsi Sharon H Giordano Grace L Smith Abigail Caudle Yu Shen Susan K Peterson Benjamin D Smith

Int J Radiat Oncol Biol Phys 2023 Sep 24. Epub 2023 Sep 24.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Purpose: Breast and skin changes are an underrecognized side effect of radiotherapy for breast cancer, which may have long-term implications for quality of life (QOL). Racial and ethnic disparities in breast cancer outcomes including long-term QOL differences following breast radiotherapy are poorly understood.

Methods And Materials: We conducted a cross-sectional survey study of patients from the XYZ Cancer Registry diagnosed with stage 0-II breast cancer from 2009-2014 and treated with lumpectomy and radiotherapy; 2,770 patients were sampled and 631 responded (23%). The BREAST-Q Adverse Effects of Radiation (AER) overall score and subindices measured the impact of radiotherapy on breast tissue. Multivariable logistic regression evaluated associations of demographic and treatment characteristics with outcomes.

Results: The median age was 57 years (IQR 48-65), median time from diagnosis to survey response 9 years (IQR 7-10), and the cohort included 62 (9.8%) Asian American or Pacific Islander, 11 (1.7%) American Indian or Alaskan Native (AIAN), 161 (25.5%) Black, 144 (22.8%) Hispanic, and 253 (40.1%) White patients. Mean BREAST-Q AER score was worse for AIAN patients (-22.2, 95% CI -39.9 to -4.6, p=0.01), Black patients (-10.8, 95% CI -16.1 to -5.5, p<0.001), and Hispanic patients (-7.8, 95% CI -13.0 to -2.5, p=0.004) compared to White patients, age <50 compared to ≥65 (effect size -8.6, 95% CI -14.0 to -3.2, p=0.002), less than a college education (-5.8, 95% CI -10.0 to -1.6, p=0.01), bra cup size of D/E versus A/B (-5.3, 95% CI -9.9 to -0.65, p=0.03), and current smokers (-11.3, 95% CI -18.3 to -4.2, p=0.002). AIAN, Black, and Hispanic patients reported worse changes in skin pigmentation, telangiectasias, dryness, soreness, and/or irritation compared to White patients.

Conclusions: AIAN, Black, and Hispanic patients reported substantially worse long-term breast and skin QOL outcomes after radiotherapy. Additional work is needed to understand these differences and how to alleviate them.
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http://dx.doi.org/10.1016/j.ijrobp.2023.09.023DOI Listing
September 2023

PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.

Authors:
Florence Petit Mauro Longoni Julie Wells Richard S Maser Eric L Bogenschutz Matthew J Dysart Hannah T M Contreras Frederic Frénois Barbara R Pober Robin D Clark Philip F Giampietro Hilger H Ropers Hao Hu Maria Loscertales Richard Wagner Xingbin Ai Harrison Brand Anne-Sophie Jourdain Marie-Ange Delrue Brigitte Gilbert-Dussardier Louise Devisme Boris Keren David J McCulley Lu Qiao Rebecca Hernan Julia Wynn Tiana M Scott Daniel G Calame Zeynep Coban-Akdemir Patricia Hernandez

Am J Hum Genet 2023 Sep 20. Epub 2023 Sep 20.

IDDRC/TCC, Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.
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http://dx.doi.org/10.1016/j.ajhg.2023.09.002DOI Listing
September 2023

[Recent Progress of Tertiary Lymphoid Structure in Prognosis and Immunotherapy of Non-small Cell Lung Cancer].

Authors:
Ying Liu Lei Xiong Ruoxue Cai Yue Chen Jinjun Ye Bo Shen Guoren Zhou

Zhongguo Fei Ai Za Zhi 2023 Aug;26(8):615-620

The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 
Nanjing 210009, China.

Lung cancer is the leading cause of cancer death, and non-small cell lung cancer (NSCLC) accounts for 85%. Immunotherapy has significantly improved the clinical prognosis of patients with NSCLC. However, because of the complexity and heterogeneousness of the tumor microenvironment, only a subset of individuals can benefit from immunotherapy. Therefore, it is necessary to explore effective predictive biomarkers for immunotherapy of NSCLC. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ that is highly similar to secondary lymphoid organs (SLO), and the presence of TLS has been found to be closely associated with a good prognosis in immunotherapy for a variety of solid tumors, including NSCLC. This article provides a review of the prognostic role of tertiary lymphoid structures in immunotherapy of NSCLC, in order to offer references for screening suitable candidates for immunotherapy of NSCLC and develop personalized and precise treatment plans.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2023.101.23DOI Listing
August 2023

The dynamic patterns and driving factors of land use conflict in the Yellow River basin of China.

Authors:
Junxiong Mo Piling Sun Dandan Shen Nan Li Jinye Zhang Kun Wang

Environ Sci Pollut Res Int 2023 Sep 26. Epub 2023 Sep 26.

School of Geography and Tourism, Qufu Normal University, Rizhao, 276826, China.

Land use conflict, as the spatial manifestation of conflicting human-land relationship, has a profound impact on sustainable use of regional land resources. Taking the Yellow River Basin (YRB) as an example, a land use conflict assessment model was constructed based on landscape pattern indices. The dynamic patterns and driving factors of land use conflict in the YRB and the corresponding driving factors were then assessed from 2000 to 2020 based on spatial autocorrelation analysis and the geodetector method. Significant spatial and temporal differences in land use conflict were observed in the YRB from 2000 to 2020. During this period, the area of stable controllable decreased by 3465 km, whereas the areas of strong and extreme conflict increased by 34,964 and 13,057 km, respectively. The expansion of areas with extreme and strong conflict mostly occurred in regions with high urbanization and human activity, including northern Shaanxi, Hetao Plain, and the Yellow River Delta. The distribution of land use conflict in the YRB from 2000 to 2020 was characterized by significant spatial agglomeration; high-value cluster conflict mainly extended from the midstream area to the upstream area, whereas low-value clusters tended to be concentrated in the upstream area of the Qinghai and Qilian Mountains. The spatial and temporal differentiation in land use conflict from 2000 to 2020 was influenced by factors related to the natural environment, geographic location, social economy, and regional policy in the YRB. The effects of elevation, distance to the nearest major river, population, economic density, and per capita disposable income of residents increased continuously during the study period, whereas the influences of mean annual precipitation and ecological retreat weakened. Analysis of the interactions between driving factors showed significant dual-factor and non-liner enhancement effects on the spatial and temporal differentiation in land use conflict. The findings provide a scientific reference for the comprehensive management of national land and ecological construction in the YRB.
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http://dx.doi.org/10.1007/s11356-023-29996-3DOI Listing
September 2023

Bioherbicidal potential of Bacillus altitudinis D30202 on Avena fatua L.: a whole-genome sequencing analysis.

Authors:
Xiu-Hua Ma Shuo Shen Wei Li Jian Wang

J Appl Genet 2023 Sep 27. Epub 2023 Sep 27.

Academy of Agriculture and Forestry Sciences, Qinghai University, Xining, 810016, Qinghai, China.

Avena fatua L. (wild oat) is one of the most harmful gramineous weeds that can affect the yield and quality of infiltrating crops. Bacillus altitudinis D30202 exhibits an excellent biocontrol activity against wild oat. To elucidate the biocontrol mechanisms of B. altitudinis D30202, the genome structure of this strain was assessed via whole-genome sequencing analysis. We predicted and analyzed secondary metabolite synthesis gene clusters to elucidate the mechanisms underlying the biocontrol of weeds. The whole-genome sequencing data indicated that B. altitudinis D30202 had the genome size and GC content of 3,777,154 bp and 41.32%, respectively, and 3809 coding genes were identified. Moreover, this strain could generate several compounds with bioherbicidal activity, including 4-hydroxy-3-methoxycinnamic acid and two indole derivatives. Bioinformatics prediction and comparative genomic analysis revealed that the strain had 6 secondary metabolite gene clusters. Furthermore, the taxonomic position of B. altitudinis D30202 was assessed, confirming its uniqueness and novelty within the Bacillus genus. Comparative genomic analysis showed differences in gene distribution, suggesting potential adaptations to different environments. In conclusion, B. altitudinis D30202 possesses a genome with unique characteristics, encoding enzymes and pathways related to herbicidal potential and biocontrol. This study provides a reference basis for understanding the molecular mechanisms of weed inhibition.
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http://dx.doi.org/10.1007/s13353-023-00788-2DOI Listing
September 2023

Tomato growth stage modulates bacterial communities across different soil aggregate sizes and disease levels.

Authors:
Menghui Dong Eiko E Kuramae Mengli Zhao Rong Li Qirong Shen George A Kowalchuk

ISME Commun 2023 Sep 26;3(1):104. Epub 2023 Sep 26.

Ecology and Biodiversity Group, Department of Biology, Institute of Environmental Biology, Utrecht University, 3584 CH, Utrecht, The Netherlands.

Soil aggregates contain distinct physio-chemical properties across different size classes. These differences in micro-habitats support varied microbial communities and modulate the effect of plant on microbiome, which affect soil functions such as disease suppression. However, little is known about how the residents of different soil aggregate size classes are impacted by plants throughout their growth stages. Here, we examined how tomato plants impact soil aggregation and bacterial communities within different soil aggregate size classes. Moreover, we investigated whether aggregate size impacts the distribution of soil pathogen and their potential inhibitors. We collected samples from different tomato growth stages: before-planting, seedling, flowering, and fruiting stage. We measured bacterial density, community composition, and pathogen abundance using qPCR and 16 S rRNA gene sequencing. We found the development of tomato growth stages negatively impacted root-adhering soil aggregation, with a gradual decrease of large macro-aggregates (1-2 mm) and an increase of micro-aggregates (<0.25 mm). Additionally, changes in bacterial density and community composition varied across soil aggregate size classes. Furthermore, the pathogen exhibited a preference to micro-aggregates, while macro-aggregates hold a higher abundance of potential pathogen-inhibiting taxa and predicted antibiotic-associated genes. Our results indicate that the impacts of tomatoes on soil differ for different soil aggregate size classes throughout different plant growth stages, and plant pathogens and their potential inhibitors have different habitats within soil aggregate size classes. These findings highlight the importance of fine-scale heterogeneity of soil aggregate size classes in research on microbial ecology and agricultural sustainability, further research focuses on soil aggregates level could help identify candidate tax involved in suppressing pathogens in the virtual micro-habitats.
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http://dx.doi.org/10.1038/s43705-023-00312-xDOI Listing
September 2023

A twenty-year dataset of high-resolution maize distribution in China.

Authors:
Qiongyan Peng Ruoque Shen Xiangqian Li Tao Ye Jie Dong Yangyang Fu Wenping Yuan

Sci Data 2023 Sep 26;10(1):658. Epub 2023 Sep 26.

International Research Center of Big Data for Sustainable Development Goals, School of Atmospheric Sciences, Sun Yat-sen University, Zhuhai, 519082, Guangdong, China.

China is the world's second-largest maize producer, contributing 23% to global production and playing a crucial role in stabilizing the global maize supply. Therefore, accurately mapping the maize distribution in China is of great significance for regional and global food security and international cereals trade. However, it still lacks a long-term maize distribution dataset with fine spatial resolution, because the existing high spatial resolution satellite datasets suffer from data gaps caused by cloud cover, especially in humid and cloudy regions. This study aimed to produce a long-term, high-resolution maize distribution map for China (China Crop Dataset-Maize, CCD-Maize) identifying maize in 22 provinces and municipalities from 2001 to 2020. The map was produced using a high spatiotemporal resolution fused dataset and a phenology-based method called Time-Weighted Dynamic Time Warping. A validation based on 54,281 field survey samples with a 30-m resolution showed that the average user's accuracy and producer's accuracy of CCD-Maize were 77.32% and 80.98%, respectively, and the overall accuracy was 80.06% over all 22 provinces.
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http://dx.doi.org/10.1038/s41597-023-02573-6DOI Listing
September 2023

Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of promoter.

Authors:
Jinru Weng Shuo Yang Jinkang Shen Hongsen Liu Yuzi Xu Dongyun Hao Shan Wang

J Zhejiang Univ Sci B 2023 Sep 23;24(10):883-895. Epub 2023 Sep 23.

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China.

This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with in the forward strand (complex F) ismore stable than that inthereverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen-bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA‍-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.
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http://dx.doi.org/10.1631/jzus.B2200634DOI Listing
September 2023

DTR-Net: Dual-space 3D Tooth Model Reconstruction from Panoramic X-ray Images.

Authors:
Lanzhuju Mei Yu Fang Yue Zhao Xiang Sean Zhou Min Zhu Zhiming Cui Dinggang Shen

IEEE Trans Med Imaging 2023 Sep 26;PP. Epub 2023 Sep 26.

In digital dentistry, cone-beam computed tomography (CBCT) can provide complete 3D tooth models, yet suffers from a long concern of requiring excessive radiation dose and higher expense. Therefore, 3D tooth model reconstruction from 2D panoramic X-ray image is more cost-effective, and has attracted great interest in clinical applications. In this paper, we propose a novel dual-space framework, namely DTR-Net, to reconstruct 3D tooth model from 2D panoramic X-ray images in both image and geometric spaces. Specifically, in the image space, we apply a 2D-to-3D generative model to recover intensities of CBCT image, guided by a task-oriented tooth segmentation network in a collaborative training manner. Meanwhile, in the geometric space, we benefit from an implicit function network in the continuous space, learning using points to capture complicated tooth shapes with geometric properties. Experimental results demonstrate that our proposed DTR-Net achieves state-of-the-art performance both quantitatively and qualitatively in 3D tooth model reconstruction, indicating its potential application in dental practice.
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http://dx.doi.org/10.1109/TMI.2023.3313795DOI Listing
September 2023

Role of Domain-Domain Interactions on the Self-Association and Physical Stability of Monoclonal Antibodies: Effect of pH and Salt.

Authors:
Amy Y Xu Marco A Blanco Maria Monica Castellanos Curtis W Meuse Kevin Mattison Ioannis Karageorgos Harold W Hatch Vincent K Shen Joseph E Curtis

J Phys Chem B 2023 Sep 26. Epub 2023 Sep 26.

NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States.

Monoclonal antibodies (mAbs) make up a major class of biotherapeutics with a wide range of clinical applications. Their physical stability can be affected by various environmental factors. For instance, an acidic pH can be encountered during different stages of the mAb manufacturing process, including purification and storage. Therefore, understanding the behavior of flexible mAb molecules in acidic solution environments will benefit the development of stable mAb products. This study used small-angle X-ray scattering (SAXS) and complementary biophysical characterization techniques to investigate the conformational flexibility and protein-protein interactions (PPI) of a model mAb molecule under near-neutral and acidic conditions. The study also characterized the interactions between Fab and Fc fragments under the same buffer conditions to identify domain-domain interactions. The results suggest that solution pH significantly influences mAb flexibility and thus could help mAbs remain physically stable by maximizing local electrostatic repulsions when mAbs become crowded in solution. Under acidic buffer conditions, both Fab and Fc contribute to the repulsive PPI observed among the full mAb at a low ionic strength. However, as ionic strength increases, hydrophobic interactions lead to the self-association of Fc fragments and, subsequently, could affect the aggregation state of the mAb.
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http://dx.doi.org/10.1021/acs.jpcb.3c03928DOI Listing
September 2023

Plasma cells in human pancreatic ductal adenocarcinoma secrete antibodies to self-antigens.

Authors:
Min Yao Jonathan Preall Johannes Yeh Darryl J Pappin Paolo Cifani Yixin Zhao Sophia Shen Philip Moresco Brian He Hardik Patel Amber N Habowski Daniel A King Kara L Raphael Arvind Rishi Divyesh V Sejpal Matthew Weiss David Tuveson Douglas T Fearon

JCI Insight 2023 Sep 26. Epub 2023 Sep 26.

Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, United States of America.

Intratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these B cell responses are largely unknown. We sought to discover these antigens by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) sequencing of tumor-infiltrating immune cells from seven primary PDAC samples. We identified activated T and B cell responses and evidence of germinal center reactions. Ig sequencing identified plasma cell (PC) clones expressing isotype-switched and hyper-mutated Igs, suggesting the occurrence of T cell-dependent B cell responses. We assessed the reactivity of 41 recombinant antibodies that represented the products of 235 PCs and 12 B cells toward multiple cell lines and PDAC tissues, and observed frequent staining of intracellular self-antigens. Three of these antigens were identified: the filamentous actin (F-actin), the nucleic protein, RUVBL2, and the mitochondrial protein, HSPD1. Antibody titers to F-actin and HSPD1 were significantly elevated in the plasma of PDAC patients (n=59) compared to healthy donors (n=61). Thus, PCs in PDAC produce auto-antibodies reacting with intracellular self-antigens, which may result from promotion of pre-existing, autoreactive B cell responses. These observations indicate that the chronic inflammatory microenvironment of PDAC can support the adaptive immune response.
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http://dx.doi.org/10.1172/jci.insight.172449DOI Listing
September 2023

Full electrical control of multiple resistance states in van der Waals sliding multiferroic tunnel junctions.

Authors:
Jie Yang Baochun Wu Jun Zhou Jing Lu Jinbo Yang Lei Shen

Nanoscale 2023 Sep 26. Epub 2023 Sep 26.

Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117575, Singapore.

The recent development of two-dimensional magnetic and sliding-ferroelectric van der Waals (vdW) materials opens a new way to realize vdW sliding multiferroic tunnel junctions (MFTJs) for low-power nonvolatile memory applications. Here, we propose and investigate full electrical control of four nonvolatile resistance states in sliding MFTJs, Au/CrI/bilayer -BN/CrI-MnBiTe/Au, first principles. We found four stable states associated with different polarization orientations in bilayer -BN and magnetization alignment in two CrI magnetic layers, which can be controlled purely by electrical voltage and current, respectively. The MFTJ has a giant tunneling magnetoresistance (TMR) of ∼10 000% (2000% in the presence of SOC) and a sizeable tunneling electroresistance (TER) of ∼70%. The write performance is explored by spin-transfer-torque calculations which show an impressive low critical current (∼1.5 × 10 A m) to switch the magnetization of the free layer of CrI, while antiferromagnetic MnBiTe pins the reference layer with a large interfacial exchange coupling.
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http://dx.doi.org/10.1039/d3nr03951jDOI Listing
September 2023

Effects of Chaihu Shugan San on Brain Functional Network Connectivity in the Hippocampus of a Perimenopausal Depression Rat Model.

Authors:
Ruiting Huang Min Gong Xue Tan Jianying Shen You Wu Xiaoshi Cai Suying Wang Li Min Lin Gong Wenna Liang

Mol Neurobiol 2023 Sep 26. Epub 2023 Sep 26.

School of Traditional Chinese Medicine, Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, 350122, People's Republic of China.

In this study, we used Chaihu Shugan San (CSS), a traditional Chinese herbal formula, as a probe to investigate the involvement of brain functional network connectivity and hippocampus energy metabolism in perimenopausal depression. A network pharmacology approach was performed to discover the underlying mechanisms of CSS in improving perimenopausal depression, which were verified in perimenopausal depression rat models. Network pharmacology analysis indicated that complex mechanisms of energy metabolism, neurotransmitter metabolism, inflammation, and hormone metabolic processes were closely associated with the anti-depressive effects of CSS. Thus, the serum concentrations of estradiol (E), glutamate (Glu), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The brain functional network connectivity between the hippocampus and adjacent brain regions was evaluated using resting-state functional magnetic resonance imaging (fMRI). A targeted metabolomic analysis of the hippocampal tricarboxylic acid cycle was also performed to measure the changes in hippocampal energy metabolism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CSS treatment significantly improved the behavioral performance, decreased the serum Glu levels, and increased the serum 5-HT levels of PMS + CUMS rats. The brain functional connectivity between the hippocampus and other brain regions was significantly changed by PMS + CUMS processes but improved by CSS treatment. Moreover, among the metabolites in the hippocampal tricarboxylic acid cycle, the concentrations of citrate and the upregulation of isocitrate and downregulation of guanosine triphosphate (GTP) in PMS + CUMS rats could be significantly improved by CSS treatment. A brain functional network connectivity mechanism may be involved in perimenopausal depression, wherein the hippocampal tricarboxylic acid cycle plays a vital role.
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http://dx.doi.org/10.1007/s12035-023-03615-1DOI Listing
September 2023

Potential role of mesenchymal stem cells in T cell aging.

Authors:
Xianmei Zhong Jie Chen Bo Wen Xu Wu Mingxing Li Fukuan Du Yu Chen Shuai Deng Yueshui Zhao Jing Shen Zhangang Xiao

J Mol Med (Berl) 2023 Sep 26. Epub 2023 Sep 26.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, No. 1, Section 1, Xianglin Road, Longmatan District, Luzhou, 646000, Sichuan, China.

Immunosenescence occurs with progressive age. T cell aging is manifested by immunodeficiency and inflammation. The main mechanisms are thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, loss of protein stability, reduction of T cell receptor (TCR) repertoire, naïve-memory T cell ratio imbalance, T cell senescence, and lack of effector plasticity. Mesenchymal stem cells (MSCs) are thought to hold great potential as anti-aging therapy. However, the role of MCSs in T cell aging remains elusive. This review makes a tentative summary of the potential role of MSCs in the protection against T cell aging. It might provide a new idea to intervene in the aging of the immune system.
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http://dx.doi.org/10.1007/s00109-023-02371-yDOI Listing
September 2023

Factors associated with 25-hydroxyvitamin D level in Chinese hospitalized patients with systemic lupus erythematosus: a retrospective cohort study.

Authors:
Xueyi Zhang Qingqing Guo Siqin Sun Xiaojun Tang Wei Shen Jun Liang Genhong Yao Linyu Geng Shuai Ding Hongwei Chen Hong Wang Bingzhu Hua Dandan Wang Huayong Zhang Xuebing Feng Lingyun Sun Ziyi Jin

Rheumatol Int 2023 Sep 26. Epub 2023 Sep 26.

Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China.

We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio.
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http://dx.doi.org/10.1007/s00296-023-05465-5DOI Listing
September 2023

AP2XII-1 is a negative regulator of merogony and presexual commitment in .

Authors:
Fuqiang Fan Lilan Xue Xiaoyan Yin Nishith Gupta Bang Shen

mBio 2023 Sep 26:e0178523. Epub 2023 Sep 26.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University , Wuhan, Hubei, China.

A transition from the asexual to sexual development in the widespread intracellular pathogen requires stage switching in its feline (definitive) host, but the mechanisms governing this process remain elusive. Here, we demonstrate a novel apicomplexan-specific transcription factor, AP2XII-1, that controls the transition of the acutely infectious tachyzoite stage to a presexual merozoite stage. The AP2XII-1 deletion mutants are elongated and replicate as merozoites by endopolygeny instead of endodyogeny, by which tachyzoites proliferate. Besides, the parasites lacking AP2XII-1 show a merozoite-type transcriptional profile. Indeed, AP2XII-1 directly targets many stage-specific genes via its interaction with the MORC complex, eventually repressing a repertoire of sex-related transcripts in tachyzoites. In conclusion, our work identifies AP2XII-1 as a merogony repressor, provides insight into the sexual commitment of , and opens a gateway to culture the presexual stages of a model parasitic protist. IMPORTANCE Sexual development is vital for the transmission, genetic hybridization, and population evolution of apicomplexan pathogens, which include several clinically relevant parasites, such as and . Previous studies have demonstrated different morphological characteristics and division patterns between asexual and sexual stages of the parasites. However, the primary regulation is poorly understood. A transition from the asexual to the sexual stage is supposedly triggered/accompanied by rewiring of gene expression and controlled by transcription factors and chromatin modulators. Herein, we discovered a tachyzoite-specific transcriptional factor AP2XII-1, which represses the presexual development in the asexual tachyzoite stage of . Conditional knockdown of AP2XII-1 perturbs tachyzoite proliferation by endodyogeny and drives a transition to a morphologically and transcriptionally distinct merozoite stage. The results also suggest a hierarchical transcriptional regulation of sexual development by AP2 factors and provide a path to culturing merozoites and controlling inter-host transmission of .
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http://dx.doi.org/10.1128/mbio.01785-23DOI Listing
September 2023

Naples prognostic score as a predictor of outcomes in lung cancer: a systematic review and meta-analysis.

Authors:
Y-S Wang L Niu W-X Shi X-Y Li L Shen

Eur Rev Med Pharmacol Sci 2023 Sep;27(17):8144-8153

Department of Oncology, Changxing County Hospital of Traditional Chinese Medicine, Changxing Country, Zhejiang Province, China.

Objective: The Naples prognostic score (NPS) is a newly developed indicator of inflammation and nutritional status. However, its role in predicting the prognosis of lung cancer is unclear. We hereby reviewed the association between NPS and outcomes of lung cancer.

Materials And Methods: PubMed, Web of Science, Embase, and Google Scholar were searched up to 15th April 2023 for studies assessing the predictive role of NPS for overall survival (OS) and disease-free survival (DFS) in lung cancer.

Results: Seven studies were included. All were from China. One study was on small cell lung cancer, while the rest were on non-small cell lung cancer. Meta-analysis demonstrated that a high NPS score was a significant predictor of OS (HR: 3.21 95% CI: 2.27, 4.54 I2=62%) and disease-free survival (DFS) (HR: 3.81 95% CI: 2.57, 5.64 I2=65%) in lung cancer patients. Subgroup analysis based on different NPS reference values also showed similar results. The results remained significant on sensitivity analysis.

Conclusions: The NPS is a strong and independent prognostic indicator of lung cancer patients. Higher NPS scores are associated with worse OS and DFS. Further studies from non-Chinese populations are needed to supplement the results.
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http://dx.doi.org/10.26355/eurrev_202309_33574DOI Listing
September 2023

Angiographic Types of Palpebral Arteriovenous Malformations and Relevant Therapeutic Options Based on Ethanol Embolization: A Multicenter Study.

Authors:
Yuchen Shen Deming Wang Mingzhe Wen Lixin Su Xindong Fan Xitao Yang

J Endovasc Ther 2023 Sep 26:15266028231201534. Epub 2023 Sep 26.

Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Purpose: The present work aimed to determine the different angio-architectural types of palpebral arteriovenous malformations (pAVMs) and appropriate ethanol embolotherapy for each type.

Materials And Methods: This was a multi-center comparative effectiveness research retrospectively conducted from November 2012 to October 2021. A total of 70 patients with pAVMs were included, which was classified into cystic pAVMs (n=29) and diffuse pAVMs (n=41) based on the angio-architecture. Of the included patients, 17 with cystic pAVMs and 13 with diffuse pAVMs underwent ethanol embolization combined with coils (CE). The remaining participants underwent no-coil ethanol embolization (NCE). Participants had undergone 60 months of follow-up. Normality of data was tested by the D'Agostino and Pearson test. Correlation was tested by the Pearson χ test. Deterioration-free survival (DFS) rate was estimated using the Kaplan-Meier survival analysis. Multivariate Cox regression models included variables that were significant at a p value<0.05 in the univariate analysis to screen the prognostic factor.

Results: The local symptoms of pAVMs, including pulsation, warmth, red plaque, blepharoptosis, bleeding, and visual blurring, along with the devascularizational grade of angiography were recorded before and after the respective procedures. Post-treatment complications were either evaluated at the 3-month routine follow-up or were self-reported by patients. Cystic pAVMs presented with significantly different clinical and angiographic features compared with diffuse pAVMs. With CE, patients with cystic pAVMs obtained a higher devascularizational grade (p<0.0001) and better clinical outcomes (p=0.0009) than those with diffuse pAVMs. Contrarily, with NCE, patients with diffuse pAVM had better outcomes than those with cystic pAVMs (p=0.0248). Moreover, the overall DFS rate was higher in patients with cystic pAVMs (p=0.0006). Finally, the angio-architecture of pAVMs was found to independently influence its prognosis (p=0.02).

Conclusions: In pAVMs, the angio-architectural type was associated with the relative prognostic status. Ethanol embolization combined with coils was an effective method to treat cystic pAVMs, whereas NCE was more suitable for the diffuse type, further emphasizing the importance of a type-based therapeutic strategy for pAVMs.

Clinical Impact: Palpebral arteriovenous malformations (pAVMs) are rare and tricky in clinical practices. The present study has divided the pAVMs into cystic and diffuse types according to their angiographic characteristics. Ethanol embolization with (CE) or without coils (NCE) was performed on both types. CE was suitable for cystic pAVMs; whereas NCE was a better choice for diffuse pAVMs. The five-year survival analyses provided evidence of the safety and efficacy of ethanol application in pAVMs. Finally, our work demonstrated that both the short- and long-term clinical outcomes of diffuse pAVMs were poor compared to those of cystic pAVM.
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http://dx.doi.org/10.1177/15266028231201534DOI Listing
September 2023

Green Solvent Processable, Asymmetric Dopant-Free Hole Transport Layer Material for Efficient and Stable n-i-p Perovskite Solar Cells and Modules.

Authors:
Qinrong Cheng Haiyang Chen Weijie Chen Junyuan Ding Ziyuan Chen Yunxiu Shen Xiaoxiao Wu Yeyong Wu Yaowen Li Yongfang Li

Angew Chem Int Ed Engl 2023 Sep 26:e202312231. Epub 2023 Sep 26.

Soochow University, College of Chemistry, Chemical Engineering and Materials Science, CHINA.

The use of dopant-free hole transport layers (HTLs) is critical in stabilizing n-i-p perovskite solar cells (pero-SCs). However, these HTL materials are often processed with toxic solvents, which is not ideal for industrial production. Upon substituting them with green solvents, a trade-off emerges between maintaining the high crystallinity of the HTL materials and ensuring high solubility in the new solvents. In this paper, we designed a novel, linear, organic small molecule, BDT-C8-3O, by introducing an asymmetric polar oligo(ethylene glycol) side chain. This method not only overcomes the solubility limitations in green solvents but also enables stacking the conjugated main chains in two patterns, which further enhances crystallinity and hole mobility. As a result, the n-i-p pero-SCs based on chlorobenzene- or green (natural compound) solvent 3-methylcyclohexanone-processed BDT-C8-3O HTL that without any dopant delivered world-recorded PCEs of 24.11% (certified of 23.82%) and 23.53%, respectively. The devices also demonstrated remarkable operational and high-temperature stabilities, maintaining over 84% and 79.5% of their initial efficiency for 2000 h, respectively. Encouragingly, dopant-free BDT-C8-3O HTL exhibits significant advantages in large-area fabrication, achieving state-of-the-art PCEs exceeding 20% for 5×5 cm2 modules (active area: 15.64 cm2), even when processed using green solvents.
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http://dx.doi.org/10.1002/anie.202312231DOI Listing
September 2023

Utilization of OATP1B Biomarker Coproporphyrin-I to Guide Drug-Drug Interaction Risk Assessment: Evaluation by the Pharmaceutical Industry.

Authors:
Ryota Kikuchi Paresh P Chothe Xiaoyan Chu Felix Huth Kazuya Ishida Naoki Ishiguro Rongrong Jiang Hong Shen Simone H Stahl Manthena V S Varma Marie-Emilie Willemin Bridget L Morse

Clin Pharmacol Ther 2023 Sep 26. Epub 2023 Sep 26.

Department of Drug Disposition, Eli Lilly, Indianapolis, IN, USA.

Drug-drug interactions (DDIs) involving hepatic organic anion transporting polypeptides 1B1/1B3 (OATP1B) can be substantial, however, challenges remain for predicting interaction risk. Emerging evidence suggests that endogenous biomarkers, particularly coproporphyrin-I (CP-I), can be used to assess in vivo OATP1B activity. The present work under the International Consortium for Innovation and Quality in Pharmaceutical Development was aimed primarily at assessing CP-I as a biomarker for informing OATP1B DDI risk. Literature and unpublished CP-I data along with pertinent in vitro and clinical DDI information were collected to identify DDIs primarily involving OATP1B inhibition and assess the relationship between OATP1B substrate drug and CP-I exposure changes. Static models to predict changes in exposure of CP-I, as a selective OATP1B substrate, were also evaluated. Significant correlations were observed between CP-I area-under-the-curve ratio (AUCR) or maximum concentration ratio (C R) and AUCR of substrate drugs. In general, the CP-I C R was equal to or greater than the CP-I AUCR. CP-I C R <1.25 was associated with absence of OATP1B-mediated DDIs (AUCR <1.25) with no false negative predictions. CP-I C R <2 was associated with weak OATP1B-mediated DDIs (AUCR <2). A correlation was identified between CP-I exposure changes and OATP1B1 static DDI predictions. Recommendations for collecting and interpreting CP-I data are discussed, including a decision tree for guiding DDI risk assessment. In conclusion, measurement of CP-I is recommended to inform OATP1B inhibition potential. The current analysis identified changes in CP-I exposure that may be used to prioritize, delay or replace clinical DDI studies.
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http://dx.doi.org/10.1002/cpt.3062DOI Listing
September 2023

Kinetics and mechanism effects of 2D carbon supports in hydrogen spillover composites.

Authors:
Lu Han Pengfei Song Rui Zhang Liuyan Zhu Lijiang Wang Xingxing Shen Sibo Shen

Nanoscale 2023 Sep 26. Epub 2023 Sep 26.

College of Chemical Engineering, Hebei Normal University of Science and Technology, Qinhuangdao, Hebei 066004, China.

Extensive research has been performed using two-dimensional (2D) carbon materials as catalyst supports to achieve high-performance hydrogen storage composites through the hydrogen spillover phenomenon. However, the kinetics and mechanism effects of different support materials still need to be investigated. This study employed high-energy ball milling to fabricate CoS/C and CS/rGO composites with stable structures and abundant hydrogen storage sites. We explored the mechanism of hydrogen adsorption behavior through electrode kinetic studies and density functional theory calculations, revealing the intrinsic relationship between material composition, structure, and hydrogen diffusion kinetics. The 2D flakes of C and rGO support and connect CS nanoparticles, providing electron transport pathways for the composites. Theoretically, the spherical C support with less steric hindrance showed a more vital ability to increase the hydrogen adsorption capacity, while kinetically, thin film rGO offers fast channels for hydrogen diffusion. These findings contribute to our understanding of hydrogen spillover and present opportunities to investigate the synergistic effects in 2D carbon-based composites.
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http://dx.doi.org/10.1039/d3nr03268jDOI Listing
September 2023

Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma.

Authors:
Hongyan Yin Qian Yao Yi Xie Dongfeng Niu Wenya Jiang Huiying Cao Xujiao Feng Yanyan Li Yilin Li Xiaotian Zhang Lin Shen Yang Chen

Cancer Med 2023 Sep 25. Epub 2023 Sep 25.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.

Background: Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status.

Methods: 376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis.

Results: We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0, and TRG0-1N+ were not reached, whereas these of patients with TRG2-3N+ were 17.37 months (95% CI, 14.14-20.60 months) and 39.97 months (95% CI, 27.05-52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi-squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%).

Conclusion: Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.
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http://dx.doi.org/10.1002/cam4.6597DOI Listing
September 2023

Gallic Acid Ameliorates Cognitive Impairment Caused by Sleep Deprivation through Antioxidant Effect.

Authors:
Xiaogang Pang Yifan Xu Shuoxin Xie Tianshu Zhang Lin Cong Yuchen Qi Lubing Liu Qingjun Li Mei Mo Guimei Wang Xiuwei Du Hui Shen Yuanyuan Li

Exp Neurobiol 2023 Aug;32(4):285-301

Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.
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http://dx.doi.org/10.5607/en23015DOI Listing
August 2023

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

Authors:
Yun Tian Xuan Hou Wanqian Cao Lu Zhou Bin Jiao Sizhe Zhang Qiao Xiao Jin Xue Ying Wang Ling Weng Liangjuan Fang Honglan Yang Yafang Zhou Fang Yi Xiaoyu Chen Juan Du Qian Xu Li Feng Zhenhua Liu Sen Zeng Qiying Sun Nina Xie Mengchuan Luo Mengli Wang Mengqi Zhang Qiuming Zeng Shunxiang Huang Lingyan Yao Yacen Hu Hongyu Long

J Peripher Nerv Syst 2023 Sep 25. Epub 2023 Sep 25.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background And Aims: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID.

Methods: In this retrospective dual-centre study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 to 2022.

Results: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n=27) and non-muscle weakness type (n=69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC=0.989, sensitivity=92.6%, specificity=97.4%).

Interpretation: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jns.12599DOI Listing
September 2023
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