Publications by authors named "Fan Wang"

1,896 Publications

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To stay or to move? Investigation on residents' migration intention under frequent secondary disasters in Wenchuan earthquake-stricken area.

Front Public Health 2022 1;10:920233. Epub 2022 Aug 1.

School of Architectural and Engineering, Tianfu College of SWUFE, Mianyang, China.

The deterioration of the living environment caused by the earthquake is the main migration motivation of residents in the area of the secondary earthquake disaster, and their migration intention is one of the most important factors affecting residents' happiness. This paper uses 957 effective survey samples from 12 secondary geological disaster areas after the Wenchuan earthquake to research the migration intention of residents and its influencing factors. It can be found that 45.2% of residents are willing to migrate, which means they have an instinctive reaction to profit-seeking and harm-avoiding, but it has not become a realistic choice. Investigation facts and research results show that the instinctive response of profit-seeking and harm-avoiding drives residents to make different choices. The migration of residents in areas where secondary geological disasters occur is affected not only by disasters such as debris flow, landslides, and collapse, but also by many factors such as life convenience, family income, expectations for future life, gender, education level, psychological feeling. The improved life and the optimization of the economic conditions brought about by the success of post-disaster reconstruction have made the vast majority of people more confident in the future of the disaster-stricken areas, which made most people choose to stay in those areas. This paper will provide policy suggestions for residents' migration and the reconstruction of the local social governance system in secondary geological disaster areas, which is helpful to improve ecological livability and residents' happiness in the Wenchuan earthquake-stricken area.
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http://dx.doi.org/10.3389/fpubh.2022.920233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376595PMC
August 2022

Lanthanide Ion Resonance-Driven Rayleigh Scattering of Nanoparticles for Dual-Modality Interferometric Scattering Microscopy.

Adv Sci (Weinh) 2022 Aug 17:e2203354. Epub 2022 Aug 17.

School of Electrical and Data Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Ultimo, New South Wales, 2007, Australia.

Light scattering from nanoparticles is significant in nanoscale imaging, photon confinement. and biosensing. However, engineering the scattering spectrum, traditionally by modifying the geometric feature of particles, requires synthesis and fabrication with nanometre accuracy. Here it is reported that doping lanthanide ions can engineer the scattering properties of low-refractive-index nanoparticles. When the excitation wavelength matches the ion resonance frequency of lanthanide ions, the polarizability and the resulted scattering cross-section of nanoparticles are dramatically enhanced. It is demonstrated that these purposely engineered nanoparticles can be used for interferometric scattering (iSCAT) microscopy. Conceptually, a dual-modality iSCAT microscopy is further developed to identify different nanoparticle types in living HeLa cells. The work provides insight into engineering the scattering features by doping elements in nanomaterials, further inspiring exploration of the geometry-independent scattering modulation strategy.
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http://dx.doi.org/10.1002/advs.202203354DOI Listing
August 2022

Discovery and validation of tissue-specific DNA methylation as noninvasive diagnostic markers for colorectal cancer.

Clin Epigenetics 2022 Aug 16;14(1):102. Epub 2022 Aug 16.

Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.

Background: Noninvasive diagnostic markers that are capable of distinguishing patients with colorectal cancer (CRC) from healthy individuals or patients with other cancer types are lacking. We report the discovery and validation of a panel of methylation-based markers that specifically detect CRC.

Methods: This was a large-scale discovery study based on publicly available datasets coupled with a validation study where multiple types of specimens from six cohorts with CRC, other cancer types, and healthy individuals were used to identify and validate the tissue-specific methylation patterns of CRC and assess their diagnostic performance.

Results: In the discovery and validation cohort (N = 9307), ten hypermethylated CpG sites located in three genes, C20orf194, LIFR, and ZNF304, were identified as CRC-specific markers. Different analyses have suggested that these CpG sites are CRC-specific hypermethylated and play a role in transcriptional silencing of corresponding genes. A random forest model based on ten markers achieved high accuracy rates between 85.7 and 94.3% and AUCs between 0.941 and 0.970 in predicting CRC in three independent datasets and a low misclassification rate in ten other cancer types. In the in-house validation cohort (N = 354), these markers achieved consistent discriminative capabilities. In the cfDNA pilot cohort (N = 14), hypermethylation of these markers was observed in cfDNA samples from CRC patients. In the cfDNA validation cohort (N = 155), the two-gene panel yielded a sensitivity of 69.5%, specificity of 91.7%, and AUC of 0.806.

Conclusions: Hypermethylation of the ten CpG sites is a CRC-specific alteration in tissue and has the potential use as a noninvasive cfDNA marker to diagnose CRC.
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http://dx.doi.org/10.1186/s13148-022-01312-9DOI Listing
August 2022

Efficacy of adjunctive brexpiprazole on symptom clusters of major depressive disorder: A post hoc analysis of four clinical studies.

J Affect Disord 2022 Aug 12. Epub 2022 Aug 12.

Otsuka Canada Pharmaceutical Inc., Saint-Laurent, QC, Canada; Department of Pharmacology & Therapeutics, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC, Canada.

Background: Major depressive disorder (MDD) is a clinically heterogenous condition and its treatment should be individualized according to the presence of particular symptom clusters. The aim of this pooled analysis was to investigate the effects of adjunctive brexpiprazole on different symptom clusters in MDD.

Methods: Data were included from four similarly designed, short-term, randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in adults with MDD and inadequate response to 2-4 antidepressant treatments (ADTs), including 1 administered by investigators. Mean changes from baseline and Cohen's d effect sizes (ES) versus placebo were determined for the following Montgomery-Åsberg Depression Rating Scale symptom clusters: core, anhedonia, dysphoria, retardation, vegetative, loss of interest, and lassitude.

Results: Over 6 weeks, ADT + brexpiprazole 2 mg (n = 486) showed greater improvement than ADT + placebo (n = 585) for all symptom clusters: core (ES = 0.36; p < 0.0001), anhedonia (ES = 0.43; p < 0.0001), dysphoria (ES = 0.27; p < 0.0001), retardation (ES = 0.32; p < 0.0001), vegetative (ES = 0.29; p < 0.0001), loss of interest (ES = 0.30; p < 0.0001), and lassitude (ES = 0.33; p < 0.0001). Improvements of similar magnitude were observed for ADT + brexpiprazole 2-3 mg (n = 770) versus ADT + placebo (n = 788) (ES = 0.24-0.38; all clusters p < 0.0001). In most cases, improvement over ADT + placebo was observed from Week 1 onwards.

Limitations: Post hoc analysis with no adjunctive active comparator.

Conclusions: Patients receiving adjunctive brexpiprazole versus adjunctive placebo showed improvements across a range of MDD symptom clusters. Improvements appeared early (generally from Week 1) and were maintained over 6 weeks. These data indicate that adjunctive brexpiprazole may benefit multiple subtypes of patient with MDD and inadequate response to ADTs.
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http://dx.doi.org/10.1016/j.jad.2022.08.021DOI Listing
August 2022

Serum levels of IL-6 and CRP can predict the efficacy of mFOLFIRINOX in patients with advanced pancreatic cancer.

Front Oncol 2022 29;12:964115. Epub 2022 Jul 29.

Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objectives: There is an urgent need for biomarkers that predict the survival outcome of patients diagnosed with metastatic pancreatic cancer, undergoing systemic chemotherapy. This study aimed to identify biomarkers associated with the survival of mPC patients treated with modified FOLFIRINOX (mFOLFIRINOX) as first-line chemotherapy.

Methods: This was a retrospective study of 30 patients with mPC who received mFOLFIRINOX between October 2018 and March 2021. Data on carcinoembryonic antigen (CEA), cancer antigen (CA)199, interleukin (IL)-6, C-reactive protein (CRP), neutrophils, platelets, lymphocytes, and albumin were collected and dichotomized using the upper or lower limit, as appropriate. These markers were examined for their association with progression-free survival (PFS). A receiver operating characteristic (ROC) curve analysis was used to explore a suitable model to predict mFOLFIRINOX effectiveness.

Results: IL-6 and CRP levels were associated with poor progression (P = 0.004 and P = <0.001, respectively) of mPC. The high IL-6 level was an independent poor prognostic factor for PFS (HR=4.66, 95%CI: 1.32-16.37, P=0.016) in the multivariable analysis. Patients with high IL-6 levels had a shorter PFS than those with low IL-6 levels (median PFS: 257 vs. 150 days, P=0.020). An increase in IL-6 and CRP levels during chemotherapy positively correlated with disease progression (P = <0.001 for both). The model combining IL-6 with CRP levels helped predict the outcomes of mPC patients treated with mFOLFIRINOX (AUC: 0.811, 95%CI: 0.639-0.983, P=0.003).

Conclusions: The serum levels of IL-6 and CRP might be considered as valuable biomarkers in predicting the outcomes of patients with mPC who received the mFOLFIRINOX regimen.
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http://dx.doi.org/10.3389/fonc.2022.964115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372918PMC
July 2022

Inhibitory effect of ficin on Candida albicans biofilm formation and pre-formed biofilms.

BMC Oral Health 2022 Aug 13;22(1):350. Epub 2022 Aug 13.

School and Hospital of Stomatology, Wenzhou Medical University, 325027, Wenzhou, People's Republic of China.

Background: To investigate the effect of ficin, a type of proteases, on Candida albicans (C. albicans) biofilm, including forming and pre-formed biofilms.

Methods: Crystal violet tests together with colony forming unit (CFU) counts were used to detect fungal biofilm biomass. Live/dead staining of biofilms observed by confocal laser scanning microscopy was used to monitor fungal activity. Finally, gene expression of C. albicans within biofilms was assessed by qRT-PCR.

Results: According to our results, biofilm biomass was dramatically reduced by ficin in both biofilm formation and pre-formed biofilms, as revealed by the crystal violet assay and CFU count (p < 0.05). Fungal activity in biofilm formation and pre-formed biofilms was not significantly influenced by ficin according to live/dead staining. Fungal polymorphism and biofilm associated gene expression were influenced by ficin, especially in groups with prominent antibiofilm effects.

Conclusions: In summary, ficin effectively inhibited C. albicans biofilm formation and detached its preformed biofilm, and it might be used to treat C. albicans biofilm associated problems.
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http://dx.doi.org/10.1186/s12903-022-02384-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375270PMC
August 2022

Inverse Optical Torques on Dielectric Nanoparticles in Elliptically Polarized Light Waves.

Phys Rev Lett 2022 Jul;129(5):053902

Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.

Elliptically polarized light waves carry the spin angular momentum (SAM), so they can exert optical torques on nanoparticles. Usually, the rotation follows the same direction as the SAM due to momentum conservation. It is counterintuitive to observe the reversal of optical torque acting on an ordinary dielectric nanoparticle illuminated by an elliptically or circularly polarized light wave. Here, we demonstrate that negative optical torques, which are opposite to the direction of SAM, can ubiquitously emerge when elliptically polarized light waves are impinged on dielectric nanoparticles obliquely. Intriguingly, the rotation can be switched between clockwise and counterclockwise directions by controlling the incident angle of light. Our study suggests a new playground to harness polarization-dependent optical force and torque for advancing optical manipulations.
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http://dx.doi.org/10.1103/PhysRevLett.129.053902DOI Listing
July 2022

R-YOLO: A YOLO-Based Method for Arbitrary-Oriented Target Detection in High-Resolution Remote Sensing Images.

Sensors (Basel) 2022 Jul 30;22(15). Epub 2022 Jul 30.

Geomatics School of Earth Sciences and Engineering, Hohai University, Nanjing 211100, China.

In view of the existence of remote sensing images with large variations in spatial resolution, small and dense objects, and the inability to determine the direction of motion, all these components make object detection from remote sensing images very challenging. In this paper, we propose a single-stage detection network based on YOLOv5. This method introduces the MS Transformer module at the end of the feature extraction network of the original network to enhance the feature extraction capability of the network model and integrates the Convolutional Block Attention Model (CBAM) to find the attention area in dense scenes. In addition, the YOLOv5 target detection network is improved by incorporating a rotation angle approach from the a priori frame design and the bounding box regression formulation to make it suitable for rotating frame-based detection scenarios. Finally, the weighted combination of the two difficult sample mining methods is used to improve the focal loss function, so as to improve the detection accuracy. The average accuracy of the test results of the improved algorithm on the DOTA data set is 77.01%, which is higher than the previous detection algorithm. Compared with the average detection accuracy of YOLOv5, the average detection accuracy is improved by 8.83%. The experimental results show that the algorithm has higher detection accuracy than other algorithms in remote sensing scenes.
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http://dx.doi.org/10.3390/s22155716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371002PMC
July 2022

Roles of HIF-1α/BNIP3 mediated mitophagy in mitochondrial dysfunction of letrozole-induced PCOS rats.

J Mol Histol 2022 Aug 11. Epub 2022 Aug 11.

Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, 350007, China.

Mitochondrial dysfunction plays a crucial role in the pathological physiology of polycystic ovary syndrome (PCOS). Mitochondrial quality control system is vital to maintaining mitochondrial function, includes mitochondrial biosynthesis, dynamics and mitophagy. While mitophagy as a specific autophagy, plays an important role in the mitochondrial quality control system and is mediated by some signaling pathways to eliminate the excessive production of reactive oxygen species (ROS), such as hypoxia-inducible factor (HIF)-1α/B-cell lymphoma-2 adenovirus E1B 19 kDa interacting protein 3 (BNIP3). Our previous studies have found that excessive production of ROS and the decreased expression of HIF-1α in the ovaries of PCOS rats. Thus, we hypothesized that excessive ROS leads to mitochondrial dysfunction, attenuates HIF-1α/BNIP3-mediated mitophagy in the ovaries of PCOS rats, and further reduces the mitophagic defense. Firstly, the oxidative stress status was detected and found excessive ROS damages ovarian tissue in PCOS rats. Secondly, the marker proteins of mitochondrial biosynthesis/dynamics and amount were examined and found that their expression levels were abnormal, which showed that the abnormal mitochondrial quality control system leads to accumulate the excess or damaged mitochondria in PCOS ovaries. Finally, we detected the HIF-1α/BNIP3 pathway and found HIF-1α-mediated mitophagy is impaired in the ovaries of PCOS rats. Together, these results clearly demonstrated excessive ROS causes mitochondrial dysfunction via the abnormal mitochondrial quality control system, and attenuates HIF-1α/BNIP3-mediated mitophagic defense in the granulosa cells of PCOS rats, which will provide a new direction for further understanding the role of HIF-1α in the molecular mechanism of mitochondrial dysfunction in PCOS ovaries.
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http://dx.doi.org/10.1007/s10735-022-10096-4DOI Listing
August 2022

Mapping developmental regionalization and patterns of cortical surface area from 29 post-menstrual weeks to 2 years of age.

Proc Natl Acad Sci U S A 2022 Aug 8;119(33):e2121748119. Epub 2022 Aug 8.

Department of Radiology and Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.

Surface area of the human cerebral cortex expands extremely dynamically and regionally heterogeneously from the third trimester of pregnancy to 2 y of age, reflecting the spatial heterogeneity of the underlying microstructural and functional development of the cerebral cortex. However, little is known about the developmental patterns and regionalization of cortical surface area during this critical stage, due to the lack of high-quality imaging data and accurate computational tools for pediatric brain MRI data. To fill this critical knowledge gap, by leveraging 1,037 high-quality MRI scans with the age between 29 post-menstrual weeks and 24 mo from 735 pediatric subjects in two complementary datasets, i.e., the Baby Connectome Project (BCP) and the developing Human Connectome Project (dHCP), and state-of-the-art dedicated image-processing tools, we unprecedentedly parcellate the cerebral cortex into a set of distinct subdivisions purely according to the developmental patterns of the cortical surface. Our discovered developmentally distinct subdivisions correspond well to structurally and functionally meaningful regions and reveal spatially contiguous, hierarchical, and bilaterally symmetric patterns of early cortical surface expansion. We also show that high-order association subdivisions, where cortical folds emerge later during prenatal stages, undergo more dramatic cortical surface expansion during infancy, compared with the central regions, especially the sensorimotor and insula cortices, thus forming a distinct central-pole division in early cortical surface expansion. These results provide an important reference for exploring and understanding dynamic early brain development in health and disease.
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http://dx.doi.org/10.1073/pnas.2121748119DOI Listing
August 2022

Biomimetic macrophage membrane-coated gold-quantum dots with tumor microenvironment stimuli-responsive capability for tumor theranostic.

Mater Today Bio 2022 Dec 12;16:100359. Epub 2022 Jul 12.

Research Center of Pharmaceutical Preparations and Nanomedicine, College of Pharmacy, Chongqing Medical University, Chongqing, 40016, China.

Tumor microenvironment (TME) is intently related to tumor growth, progression and invasion, leading to drug resistance and insufficient therapeutic efficacy. However, remodeling TME and utilizing TME for exploring intelligent nanomaterials that can realize tumor theranostic is still challenging. Nowadays, the theranostic based on chemotherapy exposes some deficiencies, such as low targeting, weak permeability and premature clearance. Furthermore, it is challenging to cure drug-resistant tumors effectively. For the sake of solving these problems, a biomimetic decomposable nano-theranostic (MMV-Au-CDs-DOX) was well-established in this work. The Au-CDs are coated with macrophage-derived microvesicle to realize drug release accurately and enhance the biocompatibility of internal nanoparticles. Furthermore, MMV-Au-CDs-DOX would locate in the inflammation position of tumor, and disintegrate correspondingly into pieces with certain different functions stimulated by TME. Subsequently, the released anti-tumor nanodrugs were used for multimodal therapy, including chemotherapy and hemodynamic therapy. In addition, combined with the ability of Au-CDs to recognize GSH specifically, the off-on fluorescent probe was constructed to monitor the GSH of tumor cells and provided information on chemotherapy resistance.
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http://dx.doi.org/10.1016/j.mtbio.2022.100359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352966PMC
December 2022

Human activities induce potential aquatic threats of micropollutants in Danjiangkou Reservoir, the largest artificial freshwater lake in Asia.

Sci Total Environ 2022 Aug 4:157843. Epub 2022 Aug 4.

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Freshwater biodiversity and ecosystem services may decline because of toxicant input, and other environmental variables often co-occur with contaminants to jeopardize the freshwater ecosystem. In this study, Danjiangkou Reservoir (DJKR) in central China was selected as the target research area to investigate the impact of multiple categories of micropollutants coupled with other stressors on the reservoir ecosystem. A total of 140 samples were collected from 28 sites in DJKR, and 124 micropollutants, including pesticides, organophosphate esters (OPEs), psychoactive substances, antiviral drugs, and pharmaceutical and personal care products, were quantified. A total of 108 micropollutants were detected in the water samples, with sum concentrations ranging from 82.35 ng·L to 1436.57 ng·L, and 71 of them had a detection frequency above 50 %, indicating the prevailing micropollutant contamination in the reservoir. The most severe pollution and risks were observed in the tributaries of DJKR. Pesticides (neonicotinoid and triazine) and OPEs were the major contributors to the ecological risk in the reservoir. Insecticides, herbicides, and OPEs accounted for the majority of the risks to fish, algae, and invertebrates, respectively. The determined priority pollutants should be paid increased attention. Environmental variables and human activities, such as human land use, induced the potential aquatic threats of micropollutants in DJKR. Results demonstrated that micropollutant pollution was one of the dominant pressures faced by aquatic organisms and human beings, and human activities played important roles as well.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157843DOI Listing
August 2022

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA.

BMC Cancer 2022 Aug 5;22(1):858. Epub 2022 Aug 5.

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Baiyun District, Jingxi Street, Guangzhou, 510515, People's Republic of China.

Background: Inflammatory parameters and Epstein-Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA.

Methods: A total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher's exact test.

Results: The optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters.

Conclusions: The SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.
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http://dx.doi.org/10.1186/s12885-022-09942-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356473PMC
August 2022

In vivo processing of digital information molecularly with targeted specificity and robust reliability.

Sci Adv 2022 Aug 5;8(31):eabo7415. Epub 2022 Aug 5.

Department of Chemistry, Tsinghua University, Beijing, China.

DNA has attracted increasing interest as an appealing medium for information storage. However, target-specific rewriting of the digital data stored in intracellular DNA remains a grand challenge because the highly repetitive nature and uneven guanine-cytosine content render the encoded DNA sequences poorly compatible with endogenous ones. In this study, a dual-plasmid system based on gene editing tools was introduced into to process information accurately. Digital data containing large repeat units in binary codes, such as text, codebook, or image, were involved in the realization of target-specific rewriting in vivo, yielding up to 94% rewriting reliability. An optical reporter was introduced as an advanced tool for presenting data processing at the molecular level. Rewritten information was stored stably and amplified over hundreds of generations. Our work demonstrates a digital-to-biological information processing approach for highly efficient data storage, amplification, and rewriting, thus robustly promoting the application of DNA-based information technology.
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http://dx.doi.org/10.1126/sciadv.abo7415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355361PMC
August 2022

Simultaneous incorporation of gallium oxide and tantalum microparticles into micro-arc oxidation coating of titanium possessing antibacterial effect and stimulating cellular response.

Biomater Adv 2022 Apr 22;135:212736. Epub 2022 Apr 22.

Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address:

Orthopedic implants with both osteogenesis and antibacterial functions are particularly promising for bone repair and substitutes. In this study, a micro-arc oxidation (MAO) coating containing titanium dioxide (TiO), gallium oxide (GaO) and tantalum oxide (TaO) on the titanium surface (MGT) was fabricated by dispersing GaO and Ta microparticles in the electrolyte. The results showed that the simultaneous incorporation of GaO and Ta microparticles into the MAO coating resulted in optimized surface performance (e.g., micro-topography, roughness, wettability, surface energy, and protein absorption) of MGT compared with pure titanium (pTi). In addition, MGT exhibited outstanding corrosion resistance owing to the presence of both GaO and Ta microparticles, which exhibit excellent corrosion resistance and their microparticles were incorporated into the micropores of the coating. Moreover, MGT with good cytocompatibility and optimized surface resulted in improved cellular responses (e.g., proliferation and osteogenic differentiation) of rat bone mesenchymal stem cells, which was attributed to Ta microparticles with outstanding osteogenic bioactivity. Furthermore, the excellent antibacterial effect of MGT was attributed to the slow release of Ga from the coating. Thus, the simultaneous incorporation of GaO and Ta microparticles into the MAO coating of MGT exhibited excellent cytocompatibility, osteogenic bioactivity, antibacterial functions, and corrosion resistance, suggesting that MGT possesses great potential for bone repair applications.
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http://dx.doi.org/10.1016/j.bioadv.2022.212736DOI Listing
April 2022

Ketamine induces rapid antidepressant effects via the autophagy-NLRP3 inflammasome pathway.

Psychopharmacology (Berl) 2022 Aug 4. Epub 2022 Aug 4.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Sub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD). However, the mechanism underlying ketamine's antidepressant properties remains unclear. Recent studies have reported an interrelationship between autophagy and the inflammasome, both of which are involved in the pathophysiology of MDD. In this study, we assess whether ketamine exerts its antidepressant effects via an association with the autophagy-NLRP3 inflammasome pathway.

Methods: We established a depressive-like rat model by treating Wistar Kyoto rats with chronic restraint stress (CRS) for 28 days. Microglial cells from newborn Sprague-Dawley rats were used for in vitro experiments.

Results: We found sub-anesthetic ketamine treatment reversed depressive-like behavior in CRS rats. Ketamine triggered autophagy in the microglia of prefrontal cortex (PFC) and (hippocampus) HPC, with increased levels of LC3B, decreased levels of p62 protein, and elevated autophagosomes both in vivo and in vitro. Moreover, NLRP3 inflammasome activation was also inhibited by ketamine, with reduced expression of NLRP3-ASC-CASP1 assembly and decreased IL-1β levels in cerebrospinal fluid (CSF) as well as in the serum. Increased BDNF levels and synaptophysin levels were detected in the ketamine-treated group. The rapid anti-depressive effects, elevation of autophagy, reduction in NLRP3, and neuroplasticity-related factors induced by ketamine could be significantly blocked by the autophagy inhibitor Baf A1 (0.1 mg/kg).

Conclusions: Our findings demonstrate that sub-anesthetic doses of ketamine exert their antidepressant-like effects by inhibiting inflammation and initiating neuroprotection via autophagy activation. These data might help expand future investigations on the antidepressant properties of ketamine.
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http://dx.doi.org/10.1007/s00213-022-06201-wDOI Listing
August 2022

Identification of Ten-Gene Related to Lipid Metabolism for Predicting Overall Survival of Breast Invasive Carcinoma.

Contrast Media Mol Imaging 2022 11;2022:8348780. Epub 2022 Jul 11.

Medical College, Jiangsu Vocational College of Medicine, YanCheng 224000, Jiangsu, China.

Background: Predicting the risk of poor prognosis of breast cancer is crucial to treating breast cancer. This study investigated the prognostic assessment of 10 lipid metabolism-related genes constructed as breast cancer models based on this study.

Methods: The TCGA database was used to obtain clinical information and expression data of breast cancer patients, and GSEA analysis and univariate and multivariate Cox proportional risk regression models were performed to identify lipid metabolism genes closely associated with overall survival (OS) of breast cancer patients and to construct a prognostic risk score model based on lipid metabolism gene markers. The Kaplan-Meier method was used to analyze the survival status of patients with high and low-risk scores, and ROC curves assessed the accuracy of this risk score. Finally, the relationship between this risk score and clinicopathological characteristics of BRCA was analyzed in a stratified manner, and the validity of this risk score as an independent prognostic factor was determined using univariate and multivariate Cox regression analyses.

Results: One hundred and forty-four differentially expressed lipid metabolism-related genes were identified in cancer and paracancerous tissues in BRCA, 21 of which were associated with overall survival (OS) in BRCA ( < 0.05). Univariate and multivariate Cox analyses revealed that age, grade, and risk score were independent prognostic factors for BRCA. Multivariate Cox regression analysis further identified APOL4, NR1H3, SLC25A5, APOL3, OSBPL1A, DYNLT1, IMMT, MAP2K6, ZDHHC8, and RAB2A lipid metabolism-related genes as independent prognostic markers for BRCA. A prognostic risk score model was developed by labeling lipid metabolism genes with these 10 genes, and patients with BRCA with high-risk scores in the model sample had significantly worse OS than those with low-risk ( < 0.01). The ROC curve area (AUC) of this risk score model was 0.712.

Conclusion: By mining the TCGA database, we identified 10 lipid metabolism-related genes APOL4, NR1H3, SLC25A5, APOL3, OSBPL1A, DYNLT1, IMMT, MAP2K6, ZDHHC8, and RAB2A, which are closely related to the prognosis of BRCA patients, and constructed a prognostic risk scoring system based on 10 lipid metabolism genes tags.
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http://dx.doi.org/10.1155/2022/8348780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293542PMC
August 2022

Clinical Features and Prognosis of Young and Middle-Aged Adults With Skin Sebaceous Adenocarcinoma.

Dermatol Surg 2022 Aug 21;48(8):797-801. Epub 2022 Jun 21.

Department of Dermatology and Venerology, National Clinical Research Center for Geriatrics, Sichuan University West China Hospital, Chengdu, China.

Background: Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated.

Objective: To explore the clinical features and prognosis of young and middle-aged adults with SAC.

Materials And Methods: Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study.

Results: Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history.

Conclusion: An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome.
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http://dx.doi.org/10.1097/DSS.0000000000003506DOI Listing
August 2022

DTSyn: a dual-transformer-based neural network to predict synergistic drug combinations.

Brief Bioinform 2022 Aug 1. Epub 2022 Aug 1.

Baidu, Inc., 701, Na Xian Road, 201210, Shanghai, China.

Drug combination therapies are superior to monotherapy for cancer treatment in many ways. Identifying novel drug combinations by screening is challenging for the wet-lab experiments due to the time-consuming process of the enormous search space of possible drug pairs. Thus, computational methods have been developed to predict drug pairs with potential synergistic functions. Notwithstanding the success of current models, understanding the mechanism of drug synergy from a chemical-gene-tissue interaction perspective lacks study, hindering current algorithms from drug mechanism study. Here, we proposed a deep neural network model termed DTSyn (Dual Transformer encoder model for drug pair Synergy prediction) based on a multi-head attention mechanism to identify novel drug combinations. We designed a fine-granularity transformer encoder to capture chemical substructure-gene and gene-gene associations and a coarse-granularity transformer encoder to extract chemical-chemical and chemical-cell line interactions. DTSyn achieved the highest receiver operating characteristic area under the curve of 0.73, 0.78. 0.82 and 0.81 on four different cross-validation tasks, outperforming all competing methods. Further, DTSyn achieved the best True Positive Rate (TPR) over five independent data sets. The ablation study showed that both transformer encoder blocks contributed to the performance of DTSyn. In addition, DTSyn can extract interactions among chemicals and cell lines, representing the potential mechanisms of drug action. By leveraging the attention mechanism and pretrained gene embeddings, DTSyn shows improved interpretability ability. Thus, we envision our model as a valuable tool to prioritize synergistic drug pairs with chemical and cell line gene expression profile.
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http://dx.doi.org/10.1093/bib/bbac302DOI Listing
August 2022

HER2-targeted dual radiotracer approach with clinical potential for noninvasive imaging of trastuzumab-resistance caused by epitope masking.

Theranostics 2022 18;12(12):5551-5563. Epub 2022 Jul 18.

Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.

The decreased HER2-accessibility by epitope masking is a primary trastuzumab-resistance mechanism. In this study, we developed a HER2-targeted dual radiotracer approach to predict the HER2-trastuzumab engagement noninvasively. Two novel HER2-specific VHHs, MIRC208 and MIRC213, were acquired by immunizing alpaca with human HER2 protein, and were site-specifically labeled with Tc. Biodistribution and SPECT/CT imaging studies were performed in mice bearing HER2-positive and HER2-negative tumors. The HER2 binding sites of Tc-MIRC208 and Tc-MIRC213 were investigated by cell binding and SPECT/CT imaging studies. We evaluated the therapeutic predictive ability of our dual-radiotracer imaging approach for trastuzumab treatment in mice bearing MUC4-positive tumors (trastuzumab-resistant JIMT-1 and 87MUC4) and MUC4-negative tumors (trastuzumab-sensitive 7HER2 and NCI-N87). The preliminary clinical studies of Tc-MIRC208 were performed in two patients with HER2-positive breast tumors. Tc-MIRC208 and Tc-MIRC213 clearly visualized HER2-positive tumors, but not HER2-negative tumors. Tc-MIRC208 competes with trastuzumab for HER2-binding while Tc-MIRC213 recognizes HER2 on an epitope that is not masked by MUC4. The SPECT/CT studies with Tc-MIRC208 and Tc-MIRC213 clearly showed that the MUC4-negative and trastuzumab-sensitive 7HER2 and NCI-N87 tumors had very similar tumor uptake with the SUV/SUV (2 h) ratios of 1.11 ± 0.17 in 7HER2 and 1.25 ± 0.22 in NCI-N87. However, the MUC4-positive JIMT-1 tumors showed the decreased SUV/SUV (2 h) ratio (0.63 ± 0.07), which correlated well with the low response rate to trastuzumab therapy. The SUV/SUV (2 h) ratio was reduced to 0.72 ± 0.02 in MUC4-expressing NCI-N87 cells, and resulting in the decreased trastuzumab sensitivity, further supporting the correlation between the SUV/SUV (2 h) ratio and trastuzumab-sensitivity. The primary and metastatic HER2-positive lesions of patients were clearly visualized by Tc-MIRC208 SPECT at 2 h post injection. Overall, we demonstrated that the dual radiotracer imaging strategy is a valid noninvasive approach for the cancer patient selection before trastuzumab therapy. Tc-MIRC213 SPECT is utilized to quantify the tumor HER2 expression and screen HER2-positive cancer patients, while Tc-MIRC208 SPECT is used to determine the HER2-accessibility of trastuzumab. The SUV/SUV (2 h) ratio is an important biomarker to determine the responsiveness of trastuzumab therapy.
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http://dx.doi.org/10.7150/thno.74154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330517PMC
August 2022

The clinical pattern differentiates ANCA-positive infective endocarditis patients from ANCA-associated vasculitis patients: a 23 years' retrospective cohort study in China and follow-ups.

Clin Rheumatol 2022 Jul 29. Epub 2022 Jul 29.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, China.

Objectives: Patients with infective endocarditis (IE) may present rheumatic manifestations concurrent with various autoantibodies and thus mimic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study aims to characterize the specific features in a long-term cohort of ANCA-positive IE patients and to perform comparative analysis with primary AAV patients.

Methods: We performed a retrospective thorough review of 475 consecutive IE patients over 23 years, identifying 22 patients positive for proteinase 3 and/or myeloperoxidase and 36 treatment-naïve AAV patients. The clinical, laboratory, and follow-up data were collected to perform comparative analysis.

Results: Our study illustrated that ANCA-positive IE patients were younger and had a shorter duration than AAV patients. Pulmonary lesions, ENT signs, peripheral neuropath, and proteinuria were more commonly seen in AAV patients, while heart valve involvement, spleen enlargement, and cerebral hemorrhage were more typical for IE patients (all p < 0.05). Besides, ANCA-positive IE patients presented a higher level of PR3-ANCA but lower C3 (both p < 0.05). Hyperleukocytosis and thrombocytopenia were more frequently found in AAV patients (both p < 0.05). No significant difference was noticed in the survival rate.

Conclusions: Our study urges the early differential diagnosis of IE in ANCA-positive patients. It supports the claim that ANCA-positive IE patients and AAV patients do not share the same clinical spectrum. Echocardiography, serological profiles, and evaluation of multi-organ involvement might be required to improve diagnostic accuracy. Key Points •Early differential diagnosis of ANCA-positive IE from AAV is challenging even for expert rheumatologists. •Our study is so far one of the largest to include 22 ANCA-positive IE patients in one single center and spanning over 23 years. It is also the first study to include both ANCA-positive IE patients and AAV patients in one center. •Our study aides to identify a clinical picture to differentiate ANCA-Positive IE Patients from AAV Patients.
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http://dx.doi.org/10.1007/s10067-022-06313-wDOI Listing
July 2022

Identifying the Subtypes of Major Depressive Disorder Based on Somatic Symptoms: A Longitudinal Study Using Latent Profile Analysis.

Front Psychiatry 2022 12;13:759334. Epub 2022 Jul 12.

Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Two-thirds of major depressive disorder (MDD) patients initially present with somatic symptoms, yet no study has used approaches based on somatic symptoms to subtype MDD. This study aimed to classify MDD somatic symptoms and tracked the prognosis of each subtype.

Methods: Data were obtained from the study of Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD). We recruited 395 subjects who received monotherapy of mirtazapine or escitalopram and conducted 2-, 4-, 6-, 8-, and 12-week follow-up assessments ( = 311, 278, 251, 199, and 178, respectively). Latent profile analysis (LPA) was performed on somatic symptom items of the depression and somatic symptoms scale (DSSS). Generalized linear mixed models (GLMM) were used to study the longitudinal prognosis of the subtypes classed by LPA. Primary outcome measures were the Hamilton Depression Rating Scale (HAMD), HAMD score reduction rate, as well as somatic and depressive items of DSSS.

Results: Three subtypes of MDD were found, namely, depression with mild somatic symptoms (68.9%), depression with moderate somatic symptoms (19.2%), and depression with severe somatic symptoms (11.9%). Scores of HAMD ( = 3.175, = 0.001), somatic ( = 23.594, < 0.001), and depressive ( = 4.163, < 0.001) DSSS items throughout the 12-week follow-up showed statistical difference among the three subtypes. The moderate group displayed a higher HAMD-17 score and a lower reduction rate at the 6th week, and more severe depressive symptoms both at the 4th and 6th weeks.

Conclusion: The results indicate that somatic symptoms should be emphasized in patients with MDD, and more attention is needed for those with moderate somatic symptoms, which may be relevant to a worse prognosis.
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http://dx.doi.org/10.3389/fpsyt.2022.759334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314656PMC
July 2022

Stochastic models of routing strategies under the class-based storage policy in fishbone layout warehouses.

Sci Rep 2022 Jul 27;12(1):12876. Epub 2022 Jul 27.

School of Information, Beijing Wuzi University, Beijing, 101149, China.

In order to improve the picking efficiency of warehouses, shorten the time cost and promote the development of the logistics industry, this study analyzes the routing strategies in fishbone layout warehouses under the class-based storage strategy. The fishbone layout was divided into three storage areas for class A, class B, and class C items according to the proportion using the straight line, to meet the classification requirements of items. Under the class-based storage strategy, to evaluate the performance of the return routing strategy and the S-shape routing strategy, the stochastic models of the expected walking distance of the two routing strategies in the fishbone layout warehouse are established by calculating the sum of the expected walking distances in diagonal cross-aisles and picking aisles. Finally, the stochastic models of the two routing strategies are simulated and verified, and the impacts of the two routing strategies on walking distances are analyzed by comparing the expected distances under different ordering frequencies and space allocation strategies. The numerical results show that the return routing strategy has an advantage over the S-shape routing strategy when determining the relevant parameters of the fishbone layout and picking orders. Meanwhile, it also provides a theoretical basis for research on stochastic models of routing strategies in fishbone layout warehouses under the class-based storage strategy.
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http://dx.doi.org/10.1038/s41598-022-17240-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329334PMC
July 2022

Pseudorabies Virus Tegument Protein UL13 Suppresses RLR-Mediated Antiviral Innate Immunity through Regulating Receptor Transcription.

Viruses 2022 07 2;14(7). Epub 2022 Jul 2.

Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian 271018, China.

Pseudorabies virus (PRV) has evolved various strategies to escape host antiviral immune responses. However, it remains unclear whether and how PRV-encoded proteins modulate the RIG-I-like receptor (RLR)-mediated signals for immune evasion. Here, we show that the PRV tegument protein UL13 functions as an antagonist of RLR-mediated antiviral responses via suppression of the transcription of RIG-I and MDA5, but not LGP2. UL13 overexpression significantly inhibits both the mRNA and protein levels of RIG-I and MDA5, along with RIG-I- or MDA5-mediated antiviral immune responses, whereas overexpression of RIG-I or MDA5 counteracts such UL13-induced suppression. Mechanistically, UL13 suppresses the expression of RIG-I and MDA5 by inhibiting activation of the transcription factor NF-κB. Consequently, overexpression of p65 promotes the activation of and promoters. Moreover, deletion of the p65-binding sites in the promoters of or abolishes the suppression role of UL13. As a result, mutant PRV lacking UL13 elicits stronger host antiviral immune responses than PRV-WT. Hence, our results provide a novel functional role of UL13-induced suppression of host antiviral immunity through modulating receptors' transcription.
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http://dx.doi.org/10.3390/v14071465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317333PMC
July 2022

Thermal Probing Techniques for a Single Live Cell.

Sensors (Basel) 2022 Jul 7;22(14). Epub 2022 Jul 7.

School of Electronics, Peking University, Beijing 100871, China.

Temperature is a significant factor in determining and characterizing cellular metabolism and other biochemical activities. In this study, we provide a brief overview of two important technologies used to monitor the local temperatures of individual living cells: fluorescence nano-thermometry and an array of micro-/nano-sized thin-film thermocouples. We explain some key technical issues that must be addressed and optimised for further practical applications, such as in cell biology, drug selection, and novel antitumor therapy. We also offer a method for combining them into a hybrid measuring system.
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http://dx.doi.org/10.3390/s22145093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317922PMC
July 2022

Palmitic Acid-Conjugated Radiopharmaceutical for Integrin αβ-Targeted Radionuclide Therapy.

Pharmaceutics 2022 Jun 23;14(7). Epub 2022 Jun 23.

Medical Isotopes Research Center and Department of Radiation Medicine, State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Peptide receptor radionuclide therapy (PRRT) is an emerging approach for patients with unresectable or metastatic tumors. Our previously optimized RGD peptide (3PRGD) has excellent targeting specificity for a variety of integrin αβ/αβ-positive tumors and has been labeled with the therapeutic radionuclide [Lu]LuCl for targeted radiotherapy of tumors. However, the rapid clearance of [Lu]Lu-DOTA-3PRGD (Lu-3PRGD) in vivo requires two doses of 111 MBq/3 mCi to achieve effective tumor suppression, limiting its further clinical application. Albumin binders have been attached to drugs to facilitate binding to albumin in vivo to prolong the drug half-life in plasma and obtain long-term effects. In this study, we modified 3PRGD with albumin-binding palmitic acid (Palm-3PRGD) and then radiolabeled Palm-3PRGD with Lu. [Lu]Lu-DOTA-Palm-3PRGD (Lu-Palm-3PRGD) retained a specific binding affinity for integrin αβ/αβ, with an IC value of 5.13 ± 1.16 nM. Compared with Lu-3PRGD, the Lu-Palm-3PRGD circulation time in blood was more than 6 times longer (slow half-life: 73.42 min versus 11.81 min), and the tumor uptake increased more than fivefold (21.34 ± 4.65 %IA/g and 4.11 ± 0.70 %IA/g at 12 h post-injection). Thus, the significant increase in tumor uptake and tumor retention resulted in enhanced efficacy of targeted radiotherapy, and tumor growth was completely inhibited by a single and relatively lowdose of 18.5 MBq/0.5 mCi. Thus, Lu-Palm-3PRGD shows great potential for clinical application.
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http://dx.doi.org/10.3390/pharmaceutics14071327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321335PMC
June 2022

Electron delocalization triggers nonradical Fenton-like catalysis over spinel oxides.

Proc Natl Acad Sci U S A 2022 Aug 25;119(31):e2201607119. Epub 2022 Jul 25.

Chinese Academy of Sciences Key Laboratory of Urban Pollutant Conversion, Department of Environmental Science and Engineering, University of Science & Technology of China, Hefei 230026, China.

Nonradical Fenton-like catalysis offers opportunities to overcome the low efficiency and secondary pollution limitations of existing advanced oxidation decontamination technologies, but realizing this on transition metal spinel oxide catalysts remains challenging due to insufficient understanding of their catalytic mechanisms. Here, we explore the origins of catalytic selectivity of Fe-Mn spinel oxide and identify electron delocalization of the surface metal active site as the key driver of its nonradical catalysis. Through fine-tuning the crystal geometry to trigger Fe-Mn superexchange interaction at the spinel octahedra, ZnFeMnO with high-degree electron delocalization of the Mn-O unit was created to enable near 100% nonradical activation of peroxymonosulfate (PMS) at unprecedented utilization efficiency. The resulting surface-bound PMS* complex can efficiently oxidize electron-rich pollutants with extraordinary degradation activity, selectivity, and good environmental robustness to favor water decontamination applications. Our work provides a molecule-level understanding of the catalytic selectivity and bimetallic interactions of Fe-Mn spinel oxides, which may guide the design of low-cost spinel oxides for more selective and efficient decontamination applications.
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http://dx.doi.org/10.1073/pnas.2201607119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351537PMC
August 2022

Association of Fatigue With Sleep Duration and Bedtime During the Third Trimester.

Front Psychiatry 2022 6;13:925898. Epub 2022 Jul 6.

Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.

Purpose: To investigate the association between fatigue and sleep habits of pregnant women to further explore the effect of sleep duration and bedtime on fatigue during the third trimester.

Materials And Methods: A total of 465 Chinese Han pregnant women in the third trimester (after 28 weeks) with a singleton gestation were recruited. Sleep habits (such as bedtime, sleep onset latency, and night sleep duration) and the 14-item Fatigue Scale scores (FS-14, used to assess fatigue) were collected.

Results: The effects of sleep duration and bedtime on FS-14 physical and total scores were significant. FS-14 physical scores and total scores of the participants in the group of sleep before 23 o'clock (SBC) of short sleep duration (<7 h) were significantly higher as compared to the participants in the group of SBC of normal sleep duration, and those of the participants in the group of SBC of normal sleep duration were significantly lower than the participants in the group of sleep after 23 o'clock of normal sleep duration. There were negative correlations of sleep duration with FS-14 physical score and total score in the SBC of short sleep duration group.

Conclusion: Sleep less than 7 h or bedtime after 23 o'clock was associated with increased fatigue levels of pregnant women in the third trimester. Therefore, it is necessary to develop good sleep habits (enough sleep duration and early bedtime) to keep fatigue at a low level for pregnant women in the third trimester.
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http://dx.doi.org/10.3389/fpsyt.2022.925898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299247PMC
July 2022

The Protective Mechanism of Afuresertib against Esophageal Cancer.

Dis Markers 2022 14;2022:1832241. Epub 2022 Jul 14.

Department of Gastroenterology, Jinhu County People's Hospital, Huai'an, 223600 Jiangsu, China.

Esophageal cancer (EC) is a common malignant tumor of the digestive system. Exploring the molecular biological mechanism of EC will help to clarify its carcinogenesis mechanism, find important molecular targets in the process of carcinogenesis, and provide new ideas for the diagnosis and treatment of EC. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the signal transduction pathways most closely related to cell proliferation and apoptosis. The regulation of various downstream molecules affects the proliferation and growth of tumor cells. In this study, we determined the effect of different concentrations of afuresertib on cell viability by MTT assay and determined the effect of afuresertib on cell apoptosis by Annexin V-FITC/PI dual staining. Animal experiments verified the effects of afuresertib on VEGF, bFGF, and PI3K/Akt. Our results indicated that afuresertib is closely related to the survival, proliferation, and apoptosis of esophageal cancer cell lines. More importantly, we found that afuresertib could reduce tumor volume and mass in EC rats through in vivo experiments. In conclusion, afuresertib may exert its antitumor effect by inhibiting the expression of PI3K and Akt-related proteins in rat tumor tissues.
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http://dx.doi.org/10.1155/2022/1832241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303141PMC
July 2022

COVID-19 vaccine affects neither prothrombotic antibody profile nor thrombosis in primary antiphospholipid syndrome: a prospective study.

Rheumatology (Oxford) 2022 Jul 22. Epub 2022 Jul 22.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To explore whether inactivated COVID-19 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary antiphospholipid syndrome (APS) patients.

Methods: We enrolled 39 primary APS patients who received two doses of inactivated SARS-CoV-2 vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and four weeks after the 2nd dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments.

Results: There was no significant difference in the presence of all eleven autoantibodies detected before and four weeks after vaccination: for aCL, IgG (14 vs. 16, P= 0.64), IgM (13 vs. 19, P= 0.34), IgA (2 vs. 3, P= 0.64); anti-β2GP1, IgG (12 vs. 12, P= 1.00), IgM (5 vs. 8, P= 0.36), IgA (4 vs. 3, P= 0.69); aPS/PT IgG (13 vs. 16, P= 0.48), IgM (17 vs. 22, P= 0.26); LAC (22 vs. 28, P= 0.16); aPF4-heparin (0 vs. 0, P= 1.00), and antinuclear antibody (ANA) (23 vs. 26, P= 0.48). Notably, the distribution of aPL profile in pre- and post- vaccination cohort was not affected by SARS-CoV-2 vaccination: for patients with low-risk aPL profile (11 vs. 10, P= 0.799) and patients with high-risk aPL profile (28 vs. 29, P= 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination.

Conclusions: Inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.
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http://dx.doi.org/10.1093/rheumatology/keac400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384505PMC
July 2022
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