Publications by authors named "Yang Song"

2,456 Publications

  • Page 1 of 1

Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial.

J Gen Intern Med 2022 Aug 9. Epub 2022 Aug 9.

Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Background: Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making.

Objectives: To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001).

Conclusions: Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated.

Trial Registration: ClinicalTrials.gov Registration: NCT01206062.
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http://dx.doi.org/10.1007/s11606-022-07753-5DOI Listing
August 2022

Polybrominated diphenyl ether quinone exposure leads to ROS-driven lysosomal damage, mitochondrial dysfunction and NLRP3 inflammasome activation.

Environ Pollut 2022 Aug 6:119846. Epub 2022 Aug 6.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China. Electronic address:

Polybrominated diphenyl ethers (PBDEs) are aromatic compounds that containing bromine atoms, which possess high efficiency, good thermal stability. However, PBDEs had various known toxic effects and were characterized as persistent environmental pollutants. Exposure to a quinone-type metabolite of PBDEs (PBDEQ) is linked with excess production of intracellular reactive oxygen species (ROS) in our previous studies. Here, we observed that PBDEQ exposure led to ROS and mitochondrial dysfunction, which promoted canonical and non-canonical Nod-like receptor protein 3 (NLRP3) inflammasome activation. Further experiments demonstrated that PBDEQ exposure activated Toll-like receptors (TLRs), subsequently regulating nuclear factor kappa B (NF-κB) signaling. Moreover, lysosomal damage and K efflux were involved in PBDEQ-driven NLRP3 inflammasome activation. Our in vivo study also illustrated that PBDEQ administration induced liver inflammation in male C57BL/6J mice. Cumulatively, our current finding provided novel insights into PBDEQ-induced pro-inflammatory responses.
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http://dx.doi.org/10.1016/j.envpol.2022.119846DOI Listing
August 2022

Acute hypoxia promotes the liver angiogenesis of largemouth bass (Micropterus salmoides) by HIF - Dependent pathway.

Fish Shellfish Immunol 2022 Aug 5. Epub 2022 Aug 5.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China. Electronic address:

A 24-hour hypoxia exposure experiment was conducted to determine how hypoxia exposure induce liver angiogenesis in largemouth bass. Nitrogen (N) was pumped into water to exclude dissolved oxygen into 1.2 ± 0.2 mg/L, and liver tissues were sampled during hypoxia exposure of 0 h, 4 h, 8 h, 12 h, 24 h and re-oxygenation for 12 h. Firstly, the results showed that hypoxia exposure promoted the angiogenesis occurrence by immunohistochemical analysis of vascular endothelial growth factor receptor 2 (VEGFR2). Secondly, the concentration of vasodilation factor increased and it's activity was elevated during 8 h exposure, such as nitric oxide (NO) and nitric oxide synthase (NOS) (p < 0.05). Thirdly, hypoxia exposure promoted angiogenesis through up-regulation the expression of matrix metalloproteinase 2 (MMP-2), jagged, protein kinase B (AKT), phosphoinositide-3-kinase (PI3K), mitogen-activated protein kinase (MAPK) at 4 h; contrarily, the expression of inhibiting angiogenesis genes presented up-regulated at 8 h (p < 0.05), such as matrix metalloproteinase inhibitor-2 (TIMP-2), matrix metalloproteinase inhibitor-3 (TIMP-3). Finally, the genes and proteins that regulate angiogenesis presented obvious chronological order. Parts of them promoted the budding and extension of blood vessels were up-regulated during 4 h-8 h (p < 0.05), such as vascular endothelial growth factor a (VEGFA), VEGFR2, monocarboxylic acid transporter 1 (MCT1), CD147, prolyl hydroxylase (PHD), nuclear factor kappa-B (NF-κB); other part of them promoted blood vessel maturation were highly expressed during 12 h-24 h (p < 0.05), such as angiogenin-1 (Ang-1) and angiogenin-2 (Ang-2). In short, acute hypoxia can promote the liver angiogenesis of largemouth bass by HIF - dependent pathway.
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http://dx.doi.org/10.1016/j.fsi.2022.08.007DOI Listing
August 2022

Combined maize straw-biochar and oxalic acids induced a relay activity of abundant specific degraders for efficient phenanthrene degradation: Evidence based on the DNA-SIP technology.

Environ Pollut 2022 Aug 5:119867. Epub 2022 Aug 5.

CAS Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China; University of the Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Biochar-oxalic acid composite application (BCOA) have shown to be efficient in the remediation of polycyclic aromatic hydrocarbon (PAH)-contaminated soil, but the functional degraders and the mechanism of improving biodegradation remains unclear. In this study, with the help of stable isotope probing technology of phenanthrene (Phe), we determined that BCOA significantly improved Phe mineralization by 2.1 times, which was ascribed to the increased numbers and abundances of functional degraders. The BCOA increased contents of dissolved organic carbon and available nutrients and decreased pH values in soil, thus promoting the activity, diversity and close cooperation of the functional Phe-degraders, and stimulating their functions associated with Phe degradation. In addition, there is a relay activity among more and diverse functional Phe-degraders in the soil with BCOA. Specifically, Pullulanibacillus persistently participated in Phe-degradation in the soil with BCOA throughout the incubation period. Moreover, Pullulanibacillus, Blastococcus, Alsobacter, Ramlibacter, and Mizugakiibacter were proved to be potential Phe-degraders in soil for the first time. The specific Phe degraders and their relay and cooperation activity in soils as impacted by BCOA were first identified with DNA-stable isotope probing technology. Our findings provided a novel perspective to understand the efficient degradation of PAH in the BCOA treatments, revealed the potential of soil native microbes in the efficient bioremediation of PAH-contaminated natural soil, and provided a basis for the development of in-situ phytoremediation technologies to remediate PAH pollution in future.
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http://dx.doi.org/10.1016/j.envpol.2022.119867DOI Listing
August 2022

Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up.

Atherosclerosis 2022 Jul 31;356:1-8. Epub 2022 Jul 31.

Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China. Electronic address:

Background And Aims: We aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome.

Methods: The primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years.

Results: This was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125-11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040).

Conclusions: LR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.
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http://dx.doi.org/10.1016/j.atherosclerosis.2022.07.013DOI Listing
July 2022

Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish.

J Exp Med 2022 Sep 8;219(9). Epub 2022 Aug 8.

Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA.

The zebrafish has proven to be a valuable model organism for studying hematopoiesis, but relatively little is known about zebrafish immune cell development and functional diversity. Elucidating key aspects of zebrafish lymphocyte development and exploring the breadth of effector functions would provide valuable insight into the evolution of adaptive immunity. We performed single-cell RNA sequencing on ∼70,000 cells from the zebrafish marrow and thymus to establish a gene expression map of zebrafish immune cell development. We uncovered rich cellular diversity in the juvenile and adult zebrafish thymus, elucidated B- and T-cell developmental trajectories, and transcriptionally characterized subsets of hematopoietic stem and progenitor cells and early thymic progenitors. Our analysis permitted the identification of two dendritic-like cell populations and provided evidence in support of the existence of a pre-B cell state. Our results provide critical insights into the landscape of zebrafish immunology and offer a foundation for cellular and genetic studies.
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http://dx.doi.org/10.1084/jem.20220038DOI Listing
September 2022

Abdominal massage alleviates functional diarrhea in immature rats via modulation of intestinal microbiota and tight junction protein.

Front Pediatr 2022 22;10:922799. Epub 2022 Jul 22.

School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou, China.

Functional diarrhea (FD) is a common type of chronic diarrhea in children. Recurrent diarrhea can negatively impact children's quality of life and raise healthcare costs significantly. However, conventional treatments are ineffective and limited. Moreover, children with chronic conditions have poor medication compliance. Therefore, non-pharmacological and complementary treatments are urgently needed. In China, abdominal massage is widely used to treat diarrhea in children. Numerous clinical studies have verified its usefulness in treating gastrointestinal disorders as well. Nevertheless, its intrinsic mechanisms are still unclear, and the impact of massage direction on treatment effects has received less attention. In our study, we found that FD was not associated with pathogen infection. A dysbiosis of the intestinal microbiota and disruption of the intestinal barrier are most likely to cause FD. Moreover, this study also substantiates that abdominal massage can mitigate functional diarrhea by altering the intestinal microbiota structure and decreasing the number of bacteria that damage intestinal mucosal barriers. The reduction of and at the genus level potentially mediated the beneficial effects of abdominal massage on alleviating diarrhea. Furthermore, massaging from two different directions, clockwise (CW) and counter-clockwise (CCW) massage, would not significantly influence the effect of the massage on intestinal microbiota or tight junction proteins. In summary, abdominal massage is an effective complementary therapy for children suffering from functional diarrhea.
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http://dx.doi.org/10.3389/fped.2022.922799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354804PMC
July 2022

Chromosome-level genome assembly of largemouth bass (Micropterus salmoides) using PacBio and Hi-C technologies.

Sci Data 2022 08 6;9(1):482. Epub 2022 Aug 6.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

The largemouth bass (Micropterus salmoides) has become a cosmopolitan species due to its widespread introduction as game or domesticated fish. Here a high-quality chromosome-level reference genome of M. salmoides was produced by combining Illumina paired-end sequencing, PacBio single molecule sequencing technique (SMRT) and High-through chromosome conformation capture (Hi-C) technologies. Ultimately, the genome was assembled into 844.88 Mb with a contig N50 of 15.68 Mb and scaffold N50 length of 35.77 Mb. About 99.9% assembly genome sequences (844.00 Mb) could be anchored to 23 chromosomes, and 98.03% assembly genome sequences could be ordered and directed. The genome contained 38.19% repeat sequences and 2693 noncoding RNAs. A total of 26,370 protein-coding genes from 3415 gene families were predicted, of which 97.69% were functionally annotated. The high-quality genome assembly will be a fundamental resource to study and understand how M. salmoides adapt to novel and changing environments around the world, and also be expected to contribute to the genetic breeding and other research.
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http://dx.doi.org/10.1038/s41597-022-01601-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357066PMC
August 2022

Proteasomal and autophagy-mediated degradation of mutp53 proteins through mitochondria-targeting aggregation-induced-emission materials.

Acta Biomater 2022 Aug 2. Epub 2022 Aug 2.

School of Medicine, South China University of Technology, Guangzhou 510006, China. Electronic address:

Close to half of human cancers harbor point mutations in the tumor-suppressor p53 gene, giving rise to the cellular accumulation of mutant p53 (mutp53) proteins with novel neomorphic gain-of-function (GOF) properties. The destruction of mutp53 proteins through either autophagic or proteasomal degradation is a viable strategy for the targeted therapy of p53-mutated cancers. Several nanomaterials, including zinc-iron and ZIF-8 nanoparticles (NPs), have been reported to induce the proteasomal degradation of mutp53 proteins. However, how autophagy, the other major cellular degradative pathway, influences NP-induced mutp53 degradation has not been investigated. This article shows that AIE-Mit-TPP, a mitochondria-targeting material with aggregation-induced emission (AIE) characteristics, elicits ubiquitination-dependent proteasomal degradation of a broad range of mutp53 proteins. Meanwhile, AIE-Mit-TPP also induces massive mitochondrial damage and autophagy. The inhibition of autophagy further increases AIE-Mit-TPP-elicited mutp53 degradation, revealing the negative impact of autophagy on AIE-Mit-TPP-induced mutp53 degradation. As expected, the degradation of mutp53 proteins by AIE-Mit-TPP abrogated mutp53-manifested GOF, leading to reductions in cell proliferation and migration and increases in cell cycle arrest and cell death. Consequently, AIE-Mit-TPP inhibited the growth of mutp53 tumors. This paper unravels the interesting interplay between the proteasomal and autophagic degradative pathways and pinpoints the modulation of autophagy as a potential strategy for optimizing NP-induced mutp53 degradation and p53-targeted cancer therapy. STATEMENT OF SIGNIFICANCE: We have designed three different types of AIE materials: non-targeting (AIE-Br), mitochondria-targeting (AIE-Mit-TPP), lysosome-targeting (AIE-Lyso). Our results proved that mitochondria-targeting AIE material induced degradation of mutp53 proteins via the proteasome degradation pathway and abrogated mutp53-conferred GOF phenotypes. Furthermore, we performed in vitro studies on the effect of the tested materials in mutp53-expressing cancer cells and demonstrated our findings via in vivo investigations in a mouse subcutaneous p53 TOV112D ovarian cancer model. Our results confirmed the link between the proteasome pathway and autophagy and thus proposed a strategy of combining AIE-Mit-TPP with autophagy inhibitors for the targeted treatment of mutp53-associated tumors. Finally, we found that AIE-Mit-TPP could induce degradation of a wide-spectrum mutp53 proteins, which makes mitochondria-targeting AIE materials an effective therapeutic strategy for p53-mutated cancers.
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http://dx.doi.org/10.1016/j.actbio.2022.07.057DOI Listing
August 2022

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors the Inhibition of Inflammation Mediated by Nitric Oxide Synthase.

Front Pharmacol 2022 19;13:920201. Epub 2022 Jul 19.

Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine nitroglycerin (NTG) injection. The experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1β, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). , XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.
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http://dx.doi.org/10.3389/fphar.2022.920201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344691PMC
July 2022

Transient nuclear deformation primes epigenetic state and promotes cell reprogramming.

Nat Mater 2022 Aug 4. Epub 2022 Aug 4.

Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.

Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation. These global changes in chromatin at the early stage of cell reprogramming boost the conversion of fibroblasts into neurons and can be partially reproduced by inhibition of histone H3 lysine 9 and DNA methylation. This mechanopriming approach also triggers macrophage reprogramming into neurons and fibroblast conversion into induced pluripotent stem cells, being thus a promising mechanically based epigenetic state modulation method for cell engineering.
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http://dx.doi.org/10.1038/s41563-022-01312-3DOI Listing
August 2022

Development and validation of a deep-learning based assistance system for enhancing laparoscopic control level.

Int J Med Robot 2022 Aug 3:e2449. Epub 2022 Aug 3.

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.

Background And Aims: Inter-operator variations in the level of intraoperative laparoscope control by surgeons influence surgical outcomes. We aimed to construct a laparoscopic surgery quantification system (LSQS) for real-time evaluation of the surgeon's laparoscope control to improve intraoperative manipulation of the laparoscope.

Methods: Using 1888 images from 80 laparoscopic videos for training, the U-Net, PSPNet, LinkNet, and DeepLabv3+ models were used to segment surgical instruments. The percentage of the instruments in central area was defined as the new indicator and the threshold was determined from 20 laparoscopic videos. The differences between expert and non-expert laparoscopic operators before and after LSQS were compared.

Results: Among the three segmentation models (U-Net, PSPNet, and LinkNet), the PSPNet model had the highest index (precision 0.9135; F1 score 0.9058; mIoU 0.8280). The validation experiment showed that LSQS could help non-expert users to more easily achieve expert-level control of the laparoscope.

Conclusions: Deep-learning technology successfully fed back real-time intraoperative information on level of laparoscope control and may facilitate better visualization of the surgical field. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/rcs.2449DOI Listing
August 2022

Are private equity and venture capital helping small and medium-sized enterprises during the COVID-19 pandemic? Evidence from China.

Authors:
Song Yang

Econ Anal Policy 2022 Dec 28;76:1-14. Epub 2022 Jul 28.

School of Mathematics and Statistics, Guizhou University of Finance and Economics, Guizhou 550025, China.

The rapid spread of COVID-19 worldwide since 2020 has, undeniably, negatively influenced the global economy and environment. Small and medium-sized enterprises (SMEs) are among the worst-hit victims of COVID-19, particularly in developing countries. As primary channels financing SMEs, what roles have private equity and venture capital (PE/VC) played in this crisis? Using the 2010-2021 data of 4462 listed companies, we aimed to assess the impact of PE/VC on financial risk among Chinese SMEs. We constructed a capital structure selection model to assess the risk preference of PE/VC and explored the roles of PE/VC in the financial risk management of enterprises during COVID-19. Based on both theory and empirical evidence, PE/VC negatively impacts the financial risk of enterprises, implying that intervention by the management of PE/VC can aggravate the financial risk. However, in reality, PE/VC positively impacted enterprise financial risk during COVID-19. Thus, the government should implement some easing policies to stimulate access and investment policies of PE/VC as well as provide more practical policies to support investment institutions in China and other counties.
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http://dx.doi.org/10.1016/j.eap.2022.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329138PMC
December 2022

Computer-aided extraction of select MRI markers of cerebral small vessel disease: A systematic review.

Neuroimage 2022 Jul 29;261:119528. Epub 2022 Jul 29.

Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine, University of New South Wales, NSW 2052, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW 2031, Australia.

Cerebral small vessel disease (CSVD) is a major vascular contributor to cognitive impairment in ageing, including dementias. Imaging remains the most promising method for in vivo studies of CSVD. To replace the subjective and laborious visual rating approaches, emerging studies have applied state-of-the-art artificial intelligence to extract imaging biomarkers of CSVD from MRI scans. We aimed to summarise published computer-aided methods for the examination of three imaging biomarkers of CSVD, namely cerebral microbleeds (CMB), dilated perivascular spaces (PVS), and lacunes of presumed vascular origin. Seventy classical image processing, classical machine learning, and deep learning studies were identified. Transfer learning and weak supervision techniques have been applied to accommodate the limitations in the training data. While good performance metrics were achieved in local datasets, there have not been generalisable pipelines validated in different research and/or clinical cohorts. Future studies could consider pooling data from multiple sources to increase data size and diversity, and evaluating performance using both image processing metrics and associations with clinical measures.
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http://dx.doi.org/10.1016/j.neuroimage.2022.119528DOI Listing
July 2022

Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma.

Cell Chem Biol 2022 Jul 20. Epub 2022 Jul 20.

State Key Laboratory of Drug Research, Centre for Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address:

The mitochondrial caseinolytic protease P (ClpP) is a target candidate for treating leukemia; however, the effects of ClpP modulation on solid tumors have not been adequately explored. Here, we report a potent activator of ClpP with the therapeutic potential for pancreatic ductal adenocarcinoma (PDAC). We first validated that aberrant ClpP activation leads to growth arrest of PDAC cells and tumors. We then performed high-throughput screening and synthetic optimization, from which we identified ZG111, a potent activator of ClpP. ZG111 binds to ClpP and promotes the ClpP-mediated degradation of respiratory chain complexes. This degradation activates the JNK/c-Jun pathway, induces the endoplasmic reticulum stress response, and consequently causes the growth arrest of PDAC cells. ZG111 also produces inhibitory effects on tumor growth in cell line-derived and patient-derived xenograft mouse models. Altogether, our data demonstrate a promising therapeutic strategy for PDAC suppression through the chemical activation of ClpP.
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http://dx.doi.org/10.1016/j.chembiol.2022.07.002DOI Listing
July 2022

Diagnostic accuracy of CRISPR technology for detecting SARS-CoV-2: a systematic review and meta-analysis.

Expert Rev Mol Diagn 2022 Aug 5:1-9. Epub 2022 Aug 5.

School of Public Health, Jilin University, Changchun, Jilin, China.

Objective: To evaluate the diagnostic accuracy of CRISPR-Cas technology for SARS-CoV-2.

Methods: RT-qPCR is defined as the reference standard. Data was collected and assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. A bivariate model for pooling was employed and subgroups analysis was used to explore heterogeneity.

Results: 2264 samples from 28 articles were extracted for evaluating the accuracy of CRISPR technology for diagnosing SARS-CoV-2. The pooled sensitivity and specificity of CRISPR technology were 0.98 (95% CI: 0.95-0.99) and 1.0 (95% CI: 0.98-1.00), respectively. High risks in patient selection bias and unclear risk of index test bias may affect accuracy. Subgroup analysis showed that CRISPR-Cas12 is applicable for molecular diagnostics for its active editing characteristics. RT-LAMP and RT-RPA are usually used for pre-amplification and fluorescence detection to output results quantitatively. Nasopharyngeal swabs and dual-genes perform greatly in our study.

Conclusion: The results concluded from all studies showed that CRISPR technology is a promising molecular method for detecting SARS-CoV-2. Standard methods including comparable sample material, patient selection, operating procedure and operators should be established.
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http://dx.doi.org/10.1080/14737159.2022.2107425DOI Listing
August 2022

Long noncoding RNA HCP5 promotes osteosarcoma cell proliferation, invasion, and migration via the miR-29b-3p-LOXL2 axis.

Kaohsiung J Med Sci 2022 Jul 28. Epub 2022 Jul 28.

Department of Orthopaedic Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan Province, China.

Osteosarcoma (OS) is the second most common primary malignant bone tumors in adolescents that causes cancer-related deaths. Previous studies have confirmed the promoting role of lncRNA HCP5 in the development of OS, but the specific mechanism is still not well understood. MiRNA levels were measured via RT-qPCR and protein expression was detected via western blotting. Cell proliferation was analyzed by CCK-8 assays and colony formations assay were conducted to measure colony formation ability. Dual-luciferase reporter assay was performed to detect the targeting relationship between HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2. Wound healing assays and Transwell assays were conducted to verify the migration and invasion abilities of OS cells. Correlations between the levels of HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2 were determined by Pearson correlation coefficient analysis. MiR-29b-3p expression was decreased and HCP5 and LOXL2 levels were increased in OS tissues and cell lines. MiR-29b-3p could directly act on LOXL2 and knockdown of LOXL2 restrained the proliferation, migration, and invasion of OS cells. Moreover, transfection with sh-HCP5-1 and sh-HCP5-2 suppressed the malignant biological behavior of OS cells. HCP5 directly targeted miR-29b-3p, and promoted OS proliferation, migration, and invasion via the miR-29b-3p/LOXL2 axis. The lncRNA HCP5 may upregulate LOXL2 expression by targeting miR-29b-3p, thereby promoting OS proliferation, migration, and invasion.
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http://dx.doi.org/10.1002/kjm2.12577DOI Listing
July 2022

Dynamic Transcriptomic Profiling During Liver Development in .

Front Physiol 2022 11;13:928858. Epub 2022 Jul 11.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.

Liver is an important organ for glucose and lipid metabolism, immunity, and detoxification in fish. However, the gene regulatory network of postnatal liver development still remains unknown in teleost fish. In this study, we performed transcriptome analysis on the liver of at three stages. A total of 1692 differentially expressed genes (DGEs) were identified across three liver developmental stages. The oil red O staining and PAS staining revealed that the lipid content of liver was increased and the glycogen content of liver was decreased during liver development. The fatty acids biosynthesis related genes were upregulated in adult and young stages compared with juvenile stage, while lipid degradation related genes were downregulated. The genes related to glycolysis, gluconeogenesis and glycogenolysis were upregulated in juvenile or young stages compared with adult stage. Further pathway analysis indicated that the CYP450 pathway, cell cycle and amino acid metabolic pathway were induced in the process of liver maturation. Our study presents the gene expression pattern in different liver development stages of and may guide future studies on metabolism of liver.
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http://dx.doi.org/10.3389/fphys.2022.928858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309550PMC
July 2022

Differentiation of Benign From Malignant Parotid Gland Tumors Using Conventional MRI Based on Radiomics Nomogram.

Front Oncol 2022 11;12:937050. Epub 2022 Jul 11.

Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Objectives: We aimed to develop and validate radiomic nomograms to allow preoperative differentiation between benign- and malignant parotid gland tumors (BPGT and MPGT, respectively), as well as between pleomorphic adenomas (PAs) and Warthin tumors (WTs).

Materials And Methods: This retrospective study enrolled 183 parotid gland tumors (68 PAs, 62 WTs, and 53 MPGTs) and divided them into training (n = 128) and testing (n = 55) cohorts. In total, 2553 radiomics features were extracted from fat-saturated T2-weighted images, apparent diffusion coefficient maps, and contrast-enhanced T1-weighted images to construct single-, double-, and multi-sequence combined radiomics models, respectively. The radiomics score (Rad-score) was calculated using the best radiomics model and clinical features to develop the radiomics nomogram. The receiver operating characteristic curve and area under the curve (AUC) were used to assess these models, and their performances were compared using DeLong's test. Calibration curves and decision curve analysis were used to assess the clinical usefulness of these models.

Results: The multi-sequence combined radiomics model exhibited better differentiation performance (BPGT . MPGT, AUC=0.863; PA . MPGT, AUC=0.929; WT . MPGT, AUC=0.825; PA . WT, AUC=0.927) than the single- and double sequence radiomics models. The nomogram based on the multi-sequence combined radiomics model and clinical features attained an improved classification performance (BPGT . MPGT, AUC=0.907; PA . MPGT, AUC=0.961; WT . MPGT, AUC=0.879; PA . WT, AUC=0.967).

Conclusions: Radiomics nomogram yielded excellent diagnostic performance in differentiating BPGT from MPGT, PA from MPGT, and PA from WT.
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http://dx.doi.org/10.3389/fonc.2022.937050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309371PMC
July 2022

Effectiveness of Augmented Reality for Lower Limb Rehabilitation: A Systematic Review.

Appl Bionics Biomech 2022 18;2022:4047845. Epub 2022 Jul 18.

Doctoral School on Safety and Security Sciences, Obuda University, Budapest 1034, Hungary.

Augmented reality- (AR-) based interventions have shown potential benefits for lower limb rehabilitation. However, current literature has not revealed these benefits as a whole. The main purposes of this systematic review were to determine the efficacy of AR-based interventions on lower limb recovery of the larger population based on the current process that has been made in this regard. Relevant studies were retrieved from five electronic databases (Web of Science, PubMed, ScienceDirect, Scopus, and Cochrane Library) using "augmented reality" OR "AR" AND "lower limb" OR "lower extremity" AND "intervention" OR "treatment". Sixteen studies that met the eligibility criteria were included in this review, and they were further grouped into three categories based on the participant types. Seven studies focused on the elderly adults, six on the stroke patients, and the last three on Parkinson patients. Based on the findings of these trials, the significant effects of AR-based interventions on lower limb rehabilitation (i.e., balance, gait, muscle, physical performance, and fall efficacy) have been initially confirmed. Favorable results were achieved at least the same as the interventions without AR except for the turning and timing in the freezing of gait of Parkinson patients. However, given the infancy of this technology in clinical practices, more robust trials with larger sample sizes and greater homogeneity in terms of devices and treatment settings are warranted for further verification.
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http://dx.doi.org/10.1155/2022/4047845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314155PMC
July 2022

Clinical efficacy analysis of 110 cases of childhood vitiligo with non-surgical combined therapy.

J Dermatolog Treat 2022 Jul 26:1-5. Epub 2022 Jul 26.

Department of Dermatology and Venerology, First Hospital of Jilin University, Changchun, China.

Background: Vitiligo has a negative effect on children's physical and psychological health. Few studies have examined long-term treatment efficacy for childhood vitiligo. Therefore, we evaluated the long-term effectiveness of non-surgical combination therapy in pediatric patients with vitiligo and analyzed factors that affect its efficacy.

Methods: Pediatric patients (⩽12 years) with vitiligo who were treated with topical corticosteroids/topical calcineurin inhibitors and phototherapy for 12 months were retrospectively studied. Short-term systemic corticosteroids were administered according to individual clinical conditions. All lesions were photographed to assess repigmentation at 3-month intervals. Clinical data, the treatment effectiveness, and factors affecting the therapeutic effect were analyzed.

Results: Overall, 110 children (51 [53.6%] girls; mean [SD] age, 7.1 ± 3.0 years; 104 [94.5%] with activity status) were treated for a mean period of 23.13 ± 14.03 months (range, 5-86 months). The overall >50% repigmentation rate was 64.5%. A longer duration of treatment was associated with a higher repigmentation rate ( = 36.229,  < .001). The vitiligo disease activity score at the first visit was positively correlated with the overall repigmentation rate ( = 0.301, = .001).

Conclusions: Treatment lasting longer than 1 year is recommended in children with vitiligo. The best repigmentation effect can be achieved by combination therapy in the rapid progression stage.
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http://dx.doi.org/10.1080/09546634.2022.2104443DOI Listing
July 2022

Influences of the Periodicity in Molecular Architecture on the Phase Diagrams and Microphase Transitions of the Janus Double-Brush Copolymer with a Loose Graft.

Polymers (Basel) 2022 Jul 13;14(14). Epub 2022 Jul 13.

Huzhou Nanxun District Jianda Ecological Environment Innovation Center, Shandong Jianzhu University, Jinan 250101, China.

The backbone of the Janus double-brush copolymer may break during long-term service, but whether this breakage affects the self-assembled phase state and microphase transitions of the material is still unknown. For the Janus double-brush copolymers with a periodicity in molecular architecture ranging from 1 to 10, the influences of the architectural periodicity on their phase diagrams and order-disorder transitions (ODT) were investigated by the self-consistent mean field theory (SCFT). In total, nine microphases with long-range order were found. By comparing the phase diagrams between copolymers of different periodicity, a decrease in periodicity or breakage along the copolymer backbone had nearly no influence on the phase diagrams unless the periodicity was too short to be smaller than 3. For copolymers with neutral backbones, a decrease in periodicity or breakage along the copolymer backbone reduced the critical segregation strengths of the whole copolymer at ODT. The equations for the critical segregation strengths at ODT, the architectural periodicity, and the volume fraction of the backbone were established for the Janus double-brush copolymers. The theoretical calculations were consistent with the previous theoretical, experimental, and simulation results.
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http://dx.doi.org/10.3390/polym14142847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320146PMC
July 2022

Contact Pattern Recognition of a Flexible Tactile Sensor Based on the CNN-LSTM Fusion Algorithm.

Micromachines (Basel) 2022 Jun 30;13(7). Epub 2022 Jun 30.

School of Electronic and Information Engineering, Anhui Jianzhu University, Hefei 230601, China.

Recognizing different contact patterns imposed on tactile sensors plays a very important role in human-machine interaction. In this paper, a flexible tactile sensor with great dynamic response characteristics is designed and manufactured based on polyvinylidene fluoride (PVDF) material. Four contact patterns (stroking, patting, kneading, and scratching) are applied to the tactile sensor, and time sequence data of the four contact patterns are collected. After that, a fusion model based on the convolutional neural network (CNN) and the long-short term memory (LSTM) neural network named CNN-LSTM is constructed. It is used to classify and recognize the four contact patterns loaded on the tactile sensor, and the recognition accuracies of the four patterns are 99.60%, 99.67%, 99.07%, and 99.40%, respectively. At last, a CNN model and a random forest (RF) algorithm model are constructed to recognize the four contact patterns based on the same dataset as those for the CNN-LSTM model. The average accuracies of the four contact patterns based on the CNN-LSTM, the CNN, and the RF algorithm are 99.43%, 96.67%, and 91.39%, respectively. All of the experimental results indicate that the CNN-LSTM constructed in this paper has very efficient performance in recognizing and classifying the contact patterns for the flexible tactile sensor.
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http://dx.doi.org/10.3390/mi13071053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317185PMC
June 2022

Effect of Heel Lift Insoles on Lower Extremity Muscle Activation and Joint Work during Barbell Squats.

Bioengineering (Basel) 2022 Jul 8;9(7). Epub 2022 Jul 8.

Faculty of Sports Science, Ningbo University, Ningbo 315211, China.

The effect of heel elevation on the barbell squat remains controversial, and further exploration of muscle activity might help find additional evidence. Therefore, 20 healthy adult participants (10 males and 10 females) were recruited for this study to analyze the effects of heel height on lower extremity kinematics, kinetics, and muscle activity using the OpenSim individualized musculoskeletal model. One-way repeated measures ANOVA was used for statistical analysis. The results showed that when the heel was raised, the participant's ankle dorsiflexion angle significantly decreased, and the percentage of ankle work was increased ( < 0.05). In addition, there was a significant increase in activation of the vastus lateralis, biceps femoris, and gastrocnemius muscles and a decrease in muscle activation of the anterior tibialis muscle ( < 0.05). An increase in knee moments and work done and a reduction in hip work were observed in male subjects ( < 0.05). In conclusion, heel raises affect lower extremity kinematics and kinetics during the barbell squat and alter the distribution of muscle activation and biomechanical loading of the joints in the lower extremity of participants to some extent, and there were gender differences in the results.
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http://dx.doi.org/10.3390/bioengineering9070301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312299PMC
July 2022

Detection and Molecular Characterization of Porcine Parvovirus 7 in Eastern Inner Mongolia Autonomous Region, China.

Front Vet Sci 2022 6;9:930123. Epub 2022 Jul 6.

Preventive Veterinary Laboratory, College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China.

Porcine parvoviruses (PPV) and porcine circoviruses type 2 (PCV2) are widespread in the pig population. Recently, it was suggested that PPV7 may stimulate PCV2 and PCV3 replication. The present study aimed to make detection and molecular characterization of PPV7 for the first time in eastern Inner Mongolia Autonomous Region, China. Twenty-seven of ninety-four samples (28.72%) and five in eight pig farms were PPV7 positive. Further detection showed that the co-infection rate of PPV7 and PCV2 was 20.21% (19/94), and 9.59% (9/94) for PPV7 and PCV3. In addition, the positive rate of PPV7 in PCV2 positive samples was higher than that in PCV2 negative samples, supporting that PCV2 could act as a co-factor for PPV7 infection. In total, four PPV7 strains were sequenced and designated as NM-14, NM-19, NM-4, and NM-40. The amplified genome sequence of NM-14 and NM-40 were 3,999nt in length, while NM-19 and NM-4 were 3,996nt with a three nucleotides deletion at 3,097-3,099, resulting in an amino acid deletion in the Cap protein. Phylogenetic analysis based on the capsid amino acid (aa) sequences showed that 52 PPV7 strains were divided into two clades, and the four PPV7 strains in this study were all clustered in clade 1. The genome and capsid amino acid sequence of the four PPV7 strains identified in this study shared 80.0-96.9% and 85.9-100% similarity with that of 48 PPV7 reference strains selected in NCBI. Simplot analysis revealed that NM-19 and NM-4 strains were probably produced by recombination of two PPV7 strains from China. The amino acid sequence alignment analysis of capsid revealed that the four PPV7 strains detected in Inner Mongolia had multiple amino acid mutations in the 6 B cell linear epitopes compared with the reference strains, suggesting that the four PPV7 strains may have different characteristics in receptor binding and immunogenicity. In summary, this paper reported the PPV7 infection and molecular characterization in the eastern of Inner Mongolia Autonomous Region for the first time, which is helpful to understand the molecular epidemic characteristics of PPV7.
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http://dx.doi.org/10.3389/fvets.2022.930123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298536PMC
July 2022

Comparison of the performance of hydrochar, raw biomass, and pyrochar as precursors to prepare porous biochar for the efficient sorption of phthalate esters.

Sci Total Environ 2022 Jul 21:157511. Epub 2022 Jul 21.

New Zealand Forest Research Institute (Scion), Christchurch 8440, New Zealand.

In this study, three high-performance porous biochars were synthesized by the cocarbonization of Pistia stratiotes-derived precursors (raw biomass, hydrochar and pyrochar) with potassium hydroxide and utilized for the sorption of diethyl phthalate from aqueous solution. The developed pore structure, surface functional groups, high hydrophobicity characteristic and graphene structure of porous biochars contributed to the excellent sorption quantity of up to 813 mg g (C, 25 mg L). Among the three precursors, hydrochar-derived porous biochar showed better properties in terms of its specific surface area and hydrophobicity, and it displayed the highest sorption capacity. The sorption kinetics and isotherm experiments confirmed that pore filling and partitioning dominated the sorption capacity while the mass transfer, hydrogen bonding and π-π stacking in the hydrochar limited the sorption rate. This finding helped to propose a feasible method for the efficient utilization of invasive aquatic plants and provided novel insight into the selection of precursors for preparing porous biochars.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157511DOI Listing
July 2022

Are active video games useful in the development of gross motor skills among non-typically developing children? A meta-analysis.

BMC Sports Sci Med Rehabil 2022 Jul 23;14(1):140. Epub 2022 Jul 23.

School of Physical Education, Shanghai University of Sport, Hengren Road 200, Shanghai, 200438, China.

Background: Proficiency in gross motor skills (GMS) lays the foundation for developing more complex motor skills. Improving these motor skills may provide enhanced opportunities for the development of a variety of perceptual, social, and cognitive skills. However, GMS development and intervention effects are not ideal for many non-typically developing children.

Objective: To systematically evaluate the effect of active video games on the development of gross motor skills in non-typically developing children and adolescents.

Methods: Seven Chinese and English databases were searched for randomized controlled trials, and the risk of bias in included studies were qualitative evaluation according to the revised Cochrane risk of bias tool for randomised trials (RoB 2). Then a meta-analysis was conducted to estimate the overall effect of active video games on the development of gross motor skills in non-typically developing children.

Results: Twenty papers were included. In the three subordinate concepts of gross motor skills, active video games significantly improved locomotor skills [ SMD = 0.59, 95% CI (0.40, 0.77)] and non-locomotor skills [SMD = 0.51, 95% CI (0.20, 0.81)] in non-typically developing children. However, there was no significant difference compared with the control group [ SMD = 0.32, 95% CI (- 0.17, 0.82)] in object control skills.

Conclusions: The study shows that active video games can improve locomotor skill and stability skill in non-typically developing children, but the effect on object control skill is uncertain, and more high-quality literature needs to be included in the future. Trial registration The meta-analysis was registered on INPLASY (202,250,124) and is available in full on inplasy.com ( https://inplasy.com/inplasy-2022-5-0124/ ).
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http://dx.doi.org/10.1186/s13102-022-00532-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308223PMC
July 2022

Eryptosis is an indicator of hematotoxicity in the risk assessment of environmental amorphous silica nanoparticles exposure: The role of macromolecule corona.

Toxicol Lett 2022 Jul 20;367:40-47. Epub 2022 Jul 20.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Rd, Haidian District, Beijing 100085, China. Electronic address:

Silica nanoparticles (SiO NPs) have been widely manufactured for various applications and unintentionally generated in various industrial processes. SiO NPs exposure is potentially hazardous to human health. Incremental evidence has indicated the presence of SiO NPs in systemic circulation, which warranted their interaction with blood components. Due to the obvious weakness of hemolysis in the risk assessment of environmental NPs, we for the first time use eryptosis as a sensitive indicator to assess the hematotoxicity of SiO NPs. In vitro results showed that the exposure of erythrocytes to pristine SiO NPs resulted in typical features of eryptosis, including oxidative stress, calcium influx, phosphatidylserine externalization and hemolysis. However, SiO NPs covered with mouse plasma ([email protected]) or grafted with polyvinylpyrrolidone ([email protected]) did not stimulate eryptosis. Interestingly, neither bare nor macromolecule-decolorated SiO NPs caused eryptosis in our in vivo mouse model, highlighting the protective role of coronal proteins on the amelioration of SiO NPs-induced hematotoxicity. These results emphasized the influences of surface modification on the toxicity of environmental NPs.
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http://dx.doi.org/10.1016/j.toxlet.2022.07.007DOI Listing
July 2022

Synergistic hydroxyl radical formation, system XC- inhibition and heat shock protein crosslinking tango in ferrotherapy: A prove-of-concept study of "sword and shield" theory.

Mater Today Bio 2022 Dec 7;16:100353. Epub 2022 Jul 7.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Rd, Haidian District, Beijing, 100085, China.

Ferroptosis provide new insights into designing nanomedicines for enhanced cancer therapy; however, its antitumor efficacy is relatively low, mainly due to self-protective mechanism of cancer cells, , heat shock protein (HSP) overexpression. Since HSPs can be modified/inhibited by lipid peroxidation (LPO) ending products, we construct a nanoplatform, namely [email protected], to amplify intracellular reactive oxygen species (ROS) and LPO for synergistic ferrotherapy. Upon tumor acidic microenvironment and local near-infrared stimuli, this nanoplatform releases FeO and reacts with intracellular hydrogen peroxide (HO) to promote Fenton reaction, and yields significant intracellular ROS (specifically hydroxyl radical, OH) and LPO. In turn, LPO ending products crosslink HSPs to destroy self-preservation pathways of cancer cells to enhance anticancer effect. Meanwhile, the released erastin inhibits system X signal pathway to depletes glutathione. FeO loading further provides magnetic resonance imaging T2-weighted signal to guide anti-tumor treatment. Together, this nanoplatform not only provides OH (as a "sword" to attack tumor cells), but also inhibits system X signal pathway and crosslinks HSP (break down the "shield" of tumor cells) to maximize synergistic ferro-therapeutic effect. [email protected] plus laser irradiation possessed highly efficient tumor suppression with magnified the levels of OH and inactive glutathione peroxidase 4 (GPX4), which can promote the development of precise cooperative cancer therapy.
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http://dx.doi.org/10.1016/j.mtbio.2022.100353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294558PMC
December 2022

County-Level Social Vulnerability is Associated With In-Hospital Death and Major Adverse Cardiovascular Events in Patients Hospitalized With COVID-19: An Analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry.

Circ Cardiovasc Qual Outcomes 2022 Jul 18:101161CIRCOUTCOMES121008612. Epub 2022 Jul 18.

Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.S.K., W.T., Y.S., R.K.W.).

Background: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the United States. However, it is unknown whether hospitalized patients with COVID-19 from socially vulnerable communities experience higher rates of death and/or major adverse cardiovascular events (MACEs). Thus, we evaluated the association between county-level social vulnerability and in-hospital mortality and MACE in a national cohort of hospitalized COVID-19 patients.

Methods: Our study population included patients with COVID-19 in the American Heart Association COVID-19 Cardiovascular Disease Registry across 107 US hospitals between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Centers for Disease Control and Prevention, was used to classify the county-level social vulnerability of patients' place of residence. We fit a hierarchical logistic regression model with hospital-level random intercepts to evaluate the association of SVI with in-hospital mortality and MACE.

Results: Among 16 939 hospitalized COVID-19 patients in the registry, 5065 (29.9%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in the lowest quartile of SVI, patients in the highest quartile were younger (age 60.2 versus 62.3 years) and more likely to be Black adults (36.7% versus 12.2%) and Medicaid-insured (31.1% versus 23.0%). After adjustment for demographics (age, sex, race/ethnicity) and insurance status, the highest quartile of SVI (compared with the lowest) was associated with higher likelihood of in-hospital mortality (OR, 1.25 [1.03-1.53]; =0.03) and MACE (OR, 1.26 [95% CI, 1.05-1.50]; =0.01). These findings were not attenuated after accounting for clinical comorbidities and acuity of illness on admission.

Conclusions: Patients hospitalized with COVID-19 residing in more socially vulnerable communities experienced higher rates of in-hospital mortality and MACE, independent of race, ethnicity, and several clinical factors. Clinical and health system strategies are needed to improve health outcomes for socially vulnerable patients.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.008612DOI Listing
July 2022
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