Publications by authors named "Bin He"

1,261 Publications

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Effectiveness of Herbal Medicine for Leukopenia/Neutropenia Induced by Chemotherapy in Adults with Colorectal Cancer: A Systematic Review and Meta-analysis.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211021654

Xiyuan Hospital,China Academy of Chinese Medical Sciences, Beijing, China.

Objective: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC).

Methods: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis.

Results: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM.

Conclusion: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.
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http://dx.doi.org/10.1177/15347354211021654DOI Listing
June 2021

MABAN: Multi-Agent Boundary-Aware Network for Natural Language Moment Retrieval.

IEEE Trans Image Process 2021 Jun 10;PP. Epub 2021 Jun 10.

The amount of videos over the Internet and electronic surveillant cameras is growing dramatically, meanwhile paired sentence descriptions are significant clues to select attentional contents from videos. The task of natural language moment retrieval (NLMR) has drawn great interests from both academia and industry, which aims to associate specific video moments with the text descriptions figuring complex scenarios and multiple activities. In general, NLMR requires temporal context to be properly comprehended, and the existing studies suffer from two problems: (1) limited moment selection and (2) insufficient comprehension of structural context. To address these issues, a multi-agent boundary-aware network (MABAN) is proposed in this work. To guarantee flexible and goal-oriented moment selection, MABAN utilizes multi-agent reinforcement learning to decompose NLMR into localizing the two temporal boundary points for each moment. Specially, MABAN employs a two-phase cross-modal interaction to exploit the rich contextual semantic information. Moreover, temporal distance regression is considered to deduce the temporal boundaries, with which the agents can enhance the comprehension of structural context. Extensive experiments are carried out on two challenging benchmark datasets of ActivityNet Captions and Charades-STA, which demonstrate the effectiveness of the proposed approach as compared to state-of-the-art methods. The project page can be found in rgb0,0,1.
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http://dx.doi.org/10.1109/TIP.2021.3086591DOI Listing
June 2021

A cross-sectional survey of preschool children: Exploring heavy metal exposure, neurotransmitters, and neurobehavioural relationships and mediation effects.

Ecotoxicol Environ Saf 2021 Jun 2;220:112391. Epub 2021 Jun 2.

School of Public Health, North China University of Science and Technology, 21 Bohai Road, Cao Fei Dian, Tangshan, Hebei 063210, China; The Laboratory Animal Center, North China University of Science and Technology, 21 Bohai Road, Cao Fei Dian, Tangshan, Hebei 063210, China. Electronic address:

Background: Exposure to heavy metals has been considered harmful and can cause cognitive deficits in preschool children.

Objective: To investigate the possible mediation effect of neurotransmitters on the relationship of heavy metal exposure with neurobehaviour.

Methods: The levels of blood heavy metals and neurotransmitters, along with the neurobehavioural scores, were determined in preschool children. Multiple linear regression was used to assess the relationship between heavy metals, neurotransmitters, and neurobehavioural scores. Furthermore, the mediating role of neurotransmitters was investigated.

Results: An interquartile range (IQR) increase in lead (6.10 μg/L) was associated with a decrease of 8.52%, 30.06%, and 20.10% for Glutamic acid (Glu), Glycine (Gly), and gamma-aminobutyric acid (GABA), respectively. An IQR increase in arsenic (19.37 μg/L) was associated with an increase of 6.32% and 2.09% for Gly and GABA, respectively. Further, an IQR increase in zinc (15.58 μg/L) was associated with an increase of 1.44% for Ser, whereas the IQR increase was associated with a decrease of 2.14%, 2.24%, and 1.89% for Glu, Gly, and GABA, respectively. An IQR increase in selenium (38.75 μg/L) was associated with an increase of 1.88% for GABA. Moreover, both Glu and Gly decreased by 2.87% for an IQR increase in manganese (16.92 μg/L). An IQR increase in mercury (15.22 μg/L) was associated with a decrease of 2.43% for Ser, but the IQR increase was associated with an increase of 4.99% and 3.09% for Gly and GABA, respectively. It was found that Glu and Serine (Ser) have a significant linear relationship with conduct score and impulsivity-hyperactivity index, and that there was a significant linear relationship between Ser and the learning disability index. GABA and conduct score and attention-deficit hyperactivity disorder (ADHD) index have a significant linear relationship. There is a significant linear relationship between Gly and conduct, anxiety, ADHD, and impulsivity-hyperactivity index. The results of the mediating effect analysis indicated that Ser, Glu, Gly, and GABA have a specific mediating effect between blood heavy metals and neurobehaviour.

Conclusion: We showed the mediating effect of neurotransmitters. The current study may provide valuable information regarding the prevention and management of metal-related neurological disorders in preschool children.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112391DOI Listing
June 2021

[Electroacupuncture combined with acupoint catgut embedding for postoperative pain after fistulotomy].

Zhen Ci Yan Jiu 2021 May;46(5):421-5

Department of Traditional Chinese Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China.

Objective: To evaluate the effect of electroacupuncture(EA) combined with acupoint catgut embedding the-rapy for postoperative pain after fistulotomy.

Methods: A total of 138 patients were randomly assigned into EA, acupoint catgut embedding and combination groups, with 46 patients in each group. The interventions were performed 30 min before surgery in all the three groups. The acupoints were Changqiang(GV1) and Chengshan(BL57). The visual analogue scale (VAS) score and limb activity score of the three groups at 6, 12, 24, 48 and 72 h after surgery, as well as maximum VAS score within 24 h(T24max VAS) of 1-3 d and total amounts of oral analgesic within 72 h after surgery were observed and recorded.

Results: The VAS score and limb activity score from the 6, 12 and 24 h after surgery, and T24max VAS score on the 1 day of the EA group were lower than those of the acupoint embedding group (<0.05). While the VAS pain score and limb activity score at the 48 h and 72 h after surgery, and T24max VAS score at the 2 to 3 day, and total dose of oral analgesic within 72 h in the acupoint embedding group were lower than those of the EA group (<0.05). The combination group was superior to the EA and acupoint embedding groups in terms of VAS score and limb activity score at different postoperative time, T24max VAS score at 1-3 d after surgery, and the total amounts of analgesic used within 72 h (<0.05).

Conclusion: EA combined with acupoint catgut embedding is more effective than simple EA or acupoint catgut embedding for postoperative pain after fistulotomy, with significant curative effect and no adverse reactions.
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http://dx.doi.org/10.13702/j.1000-0607.200603DOI Listing
May 2021

A Novel M2Ga2GeO7: N3+ (M = Ca, Ba, Sr; N = Cr, Nd, Er) Sub-micron Phosphor with Multiband NIR Emissions: Preparation, Structure, Properties, and LEDs.

Nanotechnology 2021 Jun 3. Epub 2021 Jun 3.

Chemical Engineering, Qingdao University, Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China, Qingdao, 266071, CHINA.

Near-infrared (NIR) emission materials can be widely applied in various fields, such as food detection, imaging, treatment, electronic products. With the trend of miniaturization of equipment, smaller materials are needed. In this work, we successfully synthesized a series of M2Ga2GeO7: N3+ (M = Ca, Ba, Sr; N = Cr, Nd, Er) samples and then focused on the study of Nd3+ doped Sr2Ga2GeO7 (SGGO). A series of SGGO: xNd3+ sub-micron phosphors were prepared via a microwave-assisted sol-gel process combined with subsequent calcination at 750 ℃, and the structural information and luminescent properties were systematically studied. SGGO is a representative tetragonal crystal and belonging to the space group of P4(-)21m (113). The Nd3+ ions occupy eight-coordinated Sr2+ sites in the crystal lattice. From SEM analysis, the average particle size distribution is 219.7 ± 41.4 nm. The sub-micron phosphors have rich excitation spectra ranging from 350 nm to 850 nm and can produce multiband NIR emissions of 1331, 1056, and 905 nm when excited by ultraviolet and NIR light. The maximum emission intensity was obtained by optimizing the doping ratio of Nd3+ ions. A commercial chip was then utilized to fabricate light-emitting diodes (LEDs) to verify its application potential in NIR-II mini-LEDs. Compared with blue light LEDs, the as-prepared LEDs had good imaging penetration depth and could be clearly observed under 10 mm of chicken breast coverage. The maximum imaging penetration depth can be 33 mm.
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http://dx.doi.org/10.1088/1361-6528/ac07d3DOI Listing
June 2021

Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells.

Nat Commun 2021 06 2;12(1):3285. Epub 2021 Jun 2.

Hunter James Kelly Research Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

In peripheral nerves, Schwann cells form myelin and provide trophic support to axons. We previously showed that the mitochondrial protein prohibitin 2 can localize to the axon-Schwann-cell interface and is required for developmental myelination. Whether the homologous protein prohibitin 1 has a similar role, and whether prohibitins also play important roles in Schwann cell mitochondria is unknown. Here, we show that deletion of prohibitin 1 in Schwann cells minimally perturbs development, but later triggers a severe demyelinating peripheral neuropathy. Moreover, mitochondria are heavily affected by ablation of prohibitin 1 and demyelination occurs preferentially in cells with apparent mitochondrial loss. Furthermore, in response to mitochondrial damage, Schwann cells trigger the integrated stress response, but, contrary to what was previously suggested, this response is not detrimental in this context. These results identify a role for prohibitin 1 in myelin integrity and advance our understanding about the Schwann cell response to mitochondrial damage.
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http://dx.doi.org/10.1038/s41467-021-23552-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172551PMC
June 2021

Benefits of deep learning classification of continuous noninvasive brain-computer interface control.

J Neural Eng 2021 Jun 9;18(4). Epub 2021 Jun 9.

Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, United States of America.

. Noninvasive brain-computer interfaces (BCIs) assist paralyzed patients by providing access to the world without requiring surgical intervention. Prior work has suggested that EEG motor imagery based BCI can benefit from increased decoding accuracy through the application of deep learning methods, such as convolutional neural networks (CNNs).. Here, we examine whether these improvements can generalize to practical scenarios such as continuous control tasks (as opposed to prior work reporting one classification per trial), whether valuable information remains latent outside of the motor cortex (as no prior work has compared full scalp coverage to motor only electrode montages), and the existing challenges to the practical implementation of deep-learning based continuous BCI control.. We report that: (1) deep learning methods significantly increase offline performance compared to standard methods on an independent, large, and longitudinal online motor imagery BCI dataset with up to 4-classes and continuous 2D feedback; (2) our results suggest that a variety of neural biomarkers for BCI, including those outside the motor cortex, can be detected and used to improve performance through deep learning methods, and (3) tuning neural network output will be an important step in optimizing online BCI control, as we found the CNN models trained with full scalp EEG also significantly reduce the average trial length in a simulated online cursor control environment.. This work demonstrates the benefits of CNNs classification during BCI control while providing evidence that electrode montage selection and the mapping of CNN output to device control will be important design choices in CNN based BCIs.
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http://dx.doi.org/10.1088/1741-2552/ac0584DOI Listing
June 2021

Dysfunction in Sertoli cells participates in glucocorticoid-induced impairment of spermatogenesis.

Mol Reprod Dev 2021 May 25. Epub 2021 May 25.

Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

The effect of stress on male fertility is a widespread public health issue, but less is known about the related signaling pathway. To investigate this, we established a hypercortisolism mouse model by supplementing the drinking water with corticosterone for four weeks. In the hypercortisolism mice, the serum corticosterone was much higher than in the control, and serum testosterone was significantly decreased. Moreover, corticosterone treatment induced decrease of sperm counts and increase of teratozoospermia. Increased numbers of multinucleated giant cells and apoptotic germ cells as well as downregulated meiotic markers suggested that corticosterone induced impaired spermatogenesis. Further, upregulation of macrophage-specific marker antigen F4/80 as well as inflammation-related genes suggested that corticosterone induced inflammation in the testis. Lactate content was found to be decreased in the testis and Sertoli cells after corticosterone treatment, and lactate metabolism-related genes were downregulated. In vitro phagocytosis assays showed that the phagocytic activity in corticosterone-treated Sertoli cells was downregulated and accompanied by decreased mitochondrial membrane potential, while pyruvate dehydrogenase kinase-4 inhibitor supplementation restored this process. Taken together, our results demonstrated that dysfunctional phagocytosis capacity and lactate metabolism in Sertoli cells participates in corticosterone-induced impairment of spermatogenesis.
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http://dx.doi.org/10.1002/mrd.23515DOI Listing
May 2021

Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways.

PLoS Genet 2021 May 20;17(5):e1009573. Epub 2021 May 20.

School of Life Sciences, Chongqing University, Chongqing, China.

Coordinated regulation of stress response pathways is crucial for cellular homeostasis. However, crosstalk between the different stress pathways and the physiological significance of this crosstalk remain poorly understood. In this study, using the model organism C. elegans, we discovered that suppression of the transcription factor LET-607/CREBH, a regulator of cellular defense and proteostatic responses, triggers adaptive induction of DAF-16-dependent stress responses. Suppression of LET-607 improves stress resistance and extends C. elegans lifespan in a DAF-16-dependent manner. We identified the sphingomyelin synthase SMS-5 to be a central mediator in the communication between LET-607 and DAF-16. SMS-5 reduces the contents of unsaturated phosphatidylcholine (PC), which activates DAF-16 through ITR-1-dependent calcium signaling and calcium-sensitive kinase PKC-2. Our data reveal the significance of crosstalk between different stress pathways in animal fitness and identify LET-607/CREBH and specific PC as regulators of DAF-16 and longevity.
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http://dx.doi.org/10.1371/journal.pgen.1009573DOI Listing
May 2021

injection of dual-delivery PEG based MMP-2 sensitive hydrogels for enhanced tumor penetration and chemo-immune combination therapy.

Nanoscale 2021 Jun;13(21):9577-9589

Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266073, China.

Improving the deep penetration of nanoparticles and realizing the combination of chemotherapy and immunotherapy have become a promising strategy for cancer treatment. Herein, a nuclear-targeted tetrahedral DNA nanostructure (NLS-TDNs, NT) was synthesized to construct matrix metalloproteinase (MMP-2) sensitive hydrogels as delivery vehicles with co-loaded disulfide cross-linked polyethyleneimine (PSP)/nuclear-targeted tetrahedral DNA (NLS-TDNs, NT)/doxorubicin (DOX) nanoparticles (NPs) (PSP/NT/DOX NPs and PNT/DOX NPs) and an immune adjuvant imiquimod (R837) to realize a combination of chemotherapy and immunization for metastatic breast cancer. Due to the membrane-breaking ability of the PNT/DOX NPs, the nanoparticles could effectively achieve deep penetration into tumor tissues, and the in situ generation of tumor-associated antigens by PNT/DOX elicited a strong immune response in the presence of R837, achieving a chemo-immune combination therapy of breast cancer, inducing the maturation of dendritic cells (DCs) and secretion of related cytokines, such as interleukin-6 (IL-6), interleukin-12 (IL-12p70) and tumor necrosis factor (TNF-α) in vitro. The combination significantly promoted the proportions of cytotoxic T cells (CD8+ CTL) and cytotoxic T cells/regulatory T cells (CD8+ CTL/Treg) (5.52% and 11.46%, respectively) and the secretion of cytokines, which cooperatively eradicated primary tumor growth (the tumor growth inhibition (TGI) value was 78.3%) and inhibited the tumor from metastasizing effectively in vivo. Our study provided the basis for activating the antitumor immune system to realize chemo-immunotherapy and tumor metastasis therapy.
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http://dx.doi.org/10.1039/d1nr01155cDOI Listing
June 2021

A tumor extracellular pH-sensitive PD-L1 binding peptide nanoparticle for chemo-immunotherapy of cancer.

J Mater Chem B 2021 May;9(20):4201-4210

Department of Urology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Chemo-immunotherapy is a promising model for the combination treatment of cancer. Many solid tumors overexpress programmed cell death ligand (PD-L1) for immune suppression. In this study, a PD-L1 binding peptide conjugate (DCS) nanoparticle with tumor extracellular pH-responsiveness was developed for efficient chemo-immunotherapy of colon cancer. A hydrophilic D-type polypeptide (D-PPA) and two hydrophobic stearyl chains were linked with a pH-sensitive linker to obtain amphiphilic DCS, which could self-assemble into nanoparticles (NPs). Anticancer agent doxorubicin (DOX) was loaded to obtain [email protected] NPs, which could accumulate at the tumor site by enhanced permeability and retention effect and release D-PPA at tumor extracellular pH. The release of D-PPA could not only lead to instability and aggregation of NPs for enhanced tumor retention but also block PD-1/PD-L1 to avoid immune escape and elicit enhanced immune response. In addition, DOX could induce immunogenic cell death (ICD) of cancer cells and promote anti-tumor immune response with the combination of PD-1/PD-L1 blocking. [email protected] showed efficient inhibition of CT26 tumors and induced immune response both in vitro and in vivo. Overall, our study reported a facile yet robust nanosystem based on an immune blocking peptide and a chemotherapeutic ICD inducer for efficient chemo-immunotherapy of cancer.
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http://dx.doi.org/10.1039/d1tb00537eDOI Listing
May 2021

Application and exploration of "hand as foot" teaching method in the clinical practice teaching of hydrocele.

Asian J Surg 2021 May 12. Epub 2021 May 12.

Inner Mongolia Medical University, Department of Emergency Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot North Street, Inner Mongolia, 010050, China.

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http://dx.doi.org/10.1016/j.asjsur.2021.04.036DOI Listing
May 2021

Using Weibo and WeChat social media channels to assess public awareness and practices related to antimicrobial resistance, China, 2019.

BMC Public Health 2021 05 14;21(1):921. Epub 2021 May 14.

Health Communication Center (National 12320 Health Hotline Management Office), Chinese Center for Disease Control and Prevention, No.155 Changbai Rd, Changping District, Beijing, China.

Background: Antimicrobial resistance (AMR) is a global healthcare problem, including in China where high rates of resistance to common bacterial infections have been documented. In 2016, the National Health and Family Planning Commission (NHFPC) in China established a comprehensive strategic plan to increase awareness about AMR through education programs.

Methods: We conducted an online survey to assess changes in public knowledge, awareness and practices related to AMR in China since 2016. The survey was administered using China's national and provincial level 12320 Health Hotline Weibo (micro-blog site) and WeChat (text messaging service) social media accounts from April 12, 2019 to May 7, 2019. All persons ≥16 years of age able to read Chinese were eligible to participate.

Results: A total of 2773 respondents completed the survey. Of the 2633 respondents indicating recent use of antibiotics, 84% (2223) reported obtaining their course of antibiotics from a hospital or pharmacy, 9% (246) of respondents reported using antibiotics saved from a previous prescription or treatment course, and 42% (1115) of respondents reported that they had stopped taking antibiotics as soon as they started feeling better. Most respondents correctly indicated that antibiotics can effectively treat urinary tract infections (86% [2388]) and skin infections (76% [2119]), but many incorrectly indicated that antibiotics can also treat viral infections such as measles (32% [889]) or a cold or flu (26% [726]). Of all respondents, 95% (2634) had heard of 'antibiotic resistance'. Almost half (47% [1315]) reported using antibiotics within the last 6 months.

Conclusion: While awareness of AMR was high in this survey of social media users in China, inappropriate antibiotic use remains common, including the believe that antibiotics can effectively treat viral infections. Multiple interventions targeting the correct use of antibiotics and information on the cause AMR are likely needed. The 12320 Health Hotline provides a platform for conducting routine surveys to monitor antibiotic use and knowledge about AMR.
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http://dx.doi.org/10.1186/s12889-021-10648-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120725PMC
May 2021

Vector soliton dynamics in a high-repetition-rate fiber laser.

Opt Express 2021 Apr;29(8):12049-12065

The existence of vector solitons that arise from the birefringence nature of optical fibers has been increasingly of interest for the stability of mode-locked fiber lasers, particularly for those operating in the high-fundamental-repetition-rate regime, where a large amount of fiber birefringence is required to restore the phase relation between the orthogonally polarized vector solitons, resulting in stable mode-locking free of polarization rotation. These vector solitons can exhibit diverse time-varying polarization dynamics, which prevent industrial and scientific applications requiring stable and uniform pulse trains at high fundamental repetition rates. This pressing issue, however, has so far been rarely studied. To this end, here we theoretically and experimentally dissect the formation of vector solitons in a GHz-repetition-rate fiber laser and investigate effective methods for suppressing roundtrip-to-roundtrip polarization dynamics. Our numerical model can predict both dynamic and stable regimes of high-repetition-rate mode-locking by varying the amount of fiber birefringence, resulting in the polarization rotation vector soliton (PRVS) and linearly polarized soliton (LPS), respectively. These dynamic behaviors are further studied by using an analytical approach. Interestingly, our theoretical results indicate a cavity-induced locking effect, which can be a complementary soliton trapping mechanism for the co-propagating solitons. Finally, these theoretical predications are experimentally verified, and we obtain both PRVS and LPS by adjusting the intracavity fiber birefringence.
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http://dx.doi.org/10.1364/OE.423811DOI Listing
April 2021

Biocompatible diameter-oscillating fiber with microlens endface.

Opt Express 2021 Apr;29(8):12024-12032

Optical fibers have been widely applied to life science, such as laser delivering, fluorescence collection, biosensing, bioimaging, etc. To resolve the challenges of advanced multiphoton biophotonic applications utilizing ultrashort laser pulses, here we report a flexible diameter-oscillating fiber (DOF) with microlens endface fabricated by using Polydimethylsiloxane (PDMS) elastomers. The diameter of the DOF is designed to longitudinally vary for providing accurate dispersion management, which is important for near-infrared multiphoton biophotonics that usually involves ultrashort laser pulses. The variation range and period of the DOF's diameter can be flexibly adjusted by controlling the parameters during the fabrication, such that dispersion curves with different oscillation landscapes can be obtained. The dispersion oscillating around the zero-dispersion baseline gives rise to a minimized net dispersion as the ultrashort laser pulse passes through the DOF - reducing the temporal broadening effect and resulting in transform-limited pulsewidth. In addition, the endface of the DOF is fabricated with a microlens, which is especially useful for laser scanning/focusing and fluorescence excitation. It is anticipated that this new biocompatible DOF is of great interest for biophotonic applications, particularly multiphoton microscopy deep inside biological tissues.
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http://dx.doi.org/10.1364/OE.421996DOI Listing
April 2021

Fraxinellone Has Anticancer Activity by Inducing Osteosarcoma Cell Apoptosis via Promoting Excessive Autophagy Flux.

Front Pharmacol 2021 19;12:653212. Epub 2021 Apr 19.

Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Osteosarcoma is a malignant bone tumor that is easy to metastasize in the early stage and has a very poor prognosis. Fraxinellone (FRA) is one of the main components isolated from the plant. Its anti-inflammatory and neuroprotective effects have been confirmed, but the research on the anti-cancer effect of FRA and its potential mechanism is relatively scarce. In this study, we found that FRA inhibited the proliferation and migration of osteosarcoma cells HOS and MG63 in a dose-dependent manner. Immunofluorescence, fluorescence staining and western blotting analysis showed that FRA could simultaneously induce osteosarcoma cell apoptosis and increase autophagy flux. Subsequent turnaround experiments suggested that the pro-apoptotic effect of FRA was achieved through excessive autophagy flux. The results of the xenograft orthotopic model further supported the anti-cancer effects of FRA, indicating that FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved . These studies provide new ideas for the future treatment of osteosarcoma and offer theoretical support for the anti-cancer mechanism of FRA.
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http://dx.doi.org/10.3389/fphar.2021.653212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090933PMC
April 2021

Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation.

Nat Commun 2021 05 4;12(1):2519. Epub 2021 May 4.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.
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http://dx.doi.org/10.1038/s41467-021-22743-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097024PMC
May 2021

Quality of frozen porcine Longissimus lumborum muscles injected with l-arginine and l-lysine solution.

Meat Sci 2021 Sep 28;179:108530. Epub 2021 Apr 28.

Engineering Research Center of Bio-Process, Ministry of Education, Hefei, University of Technology, Hefei 230009, Anhui, PR China; School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. Electronic address:

This study investigated the effects of l-arginine and l-lysine on the water holding capacity, shear force, color, and protein denaturation of frozen porcine Longissimus lumborum. Four batches were prepared, each corresponding to samples of an experimental treatment: without a cryoprotective solution, injecting a 0.3% sodium tripolyphosphate and 0.5% NaCl solution, a 0.5% l-arginine solution, or a 0.5% l-lysine solution. The results showed that both l-arginine and l-lysine decreased thawing loss, cooking loss, shear force, L values, b values, and surface hydrophobicity, but they increased pH values, a values, percentages of peak areas for T relaxation times, and Ca-ATPase activity. Additionally, both histological and transmission electron microscopy images showed that l-lysine, and especially l-arginine could inhibit the formation of gaps between fiber bundles, alleviate the disruption of intracellular spaces, and maintain the structural integrity of sarcomeres. Overall, the results showed that both l-arginine and l-lysine hindered the structural damage of muscle fibers during freezing and protected myofibrillar proteins from denaturation, ultimately contributing to superior quality attributes.
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http://dx.doi.org/10.1016/j.meatsci.2021.108530DOI Listing
September 2021

Thermosensitive polymer hydrogel as a physical shield on colonic mucosa for colitis treatment.

J Mater Chem B 2021 May;9(18):3874-3884

Department of Stomatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), is a chronic disease characterized by diffuse mucosal inflammation limited to the colon. Topical drug delivery systems that could be facilely performed and efficiently retained at colon sites are attractive for clinical IBD treatment. Herein, we report the exploration of an injectable thermosensitive copolymer hydrogel as a topical formulation for IBD treatment and demonstrate its feasibility in UC treatment by shielding ulcer sites from the external environment and being a drug reservoir for sustained release. Poly(aliphatic ester)-based triblock copolymer, poly(dl-lactic acid)-poly(ethylene glycol)-poly(dl-lactic acid) (PDLLA-PEG-PDLLA), adopts the solution state at room temperature yet a gel state at body temperature when the polymer concentration is more than 11%. The gel acts not only as a physical mucosal barrier for protecting ulcer sites from microorganisms like bacteria but also as a mesalazine depot for enhanced drug retention in the colon for localized, sustained drug release. In vivo UC treatment reveals that blank gel as a mucosal protector shows nearly the same treatment effect to mesalazine SR granules. Mesalazine-loaded gel significantly suppresses inflammation and has the best outcomes of indices such as colonic length, mucosal injury index, pathological tissue, and inflammatory factor. The injectable thermosensitive polymer hydrogel represents a novel, robust platform for the efficient treatment of IBD by acting as a physical shield to block out the pro-inflammatory factors as well as a drug depot for enhanced drug retention and controlled delivery.
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http://dx.doi.org/10.1039/d1tb00499aDOI Listing
May 2021

A double-layer dura mater based on poly(caprolactone--lactide) film and polyurethane sponge: preparation, characterization, and biodegradation study.

J Mater Chem B 2021 May;9(18):3863-3873

National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.

Synthetic, biodegradable polymers hold great potential in dura mater substitution. In this study, a dura mater-mimetic double-layer [email protected] composite was developed. The composite contains a poly(caprolactone-co-lactide) (PCLA) film and polyurethane (PU) sponge, which simulates the hard and soft layers of dura mater, respectively. PCLA films were prepared by a solution-casting method and showed excellent mechanical properties and tolerance to water. PU sponge was hydrophilic and had a high water-absorption rate (about 500%). The double-layer composite ([email protected]) integrated the good mechanical properties of the films and the good water absorption of the sponge. The excellent biocompatibility and biodegradability of the PCLA [email protected] sponge composites were verified by in vitro degradation and cytotoxicity study and the in vivo implantation in the back of rats. Importantly, the [email protected] composite had a suitable degradation rate and good biocompatibility, holding potential in the field of dural repair.
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http://dx.doi.org/10.1039/d1tb00454aDOI Listing
May 2021

Effective easing of the side effects of copper intrauterine devices using ultra-fine-grained Cu-0.4Mg alloy.

Acta Biomater 2021 Apr 24. Epub 2021 Apr 24.

Graduate School of Peking Union Medical College, Beijing 100730, China; Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China. Electronic address:

Copper intrauterine device is one of the most adopted contraceptive methods with high effectiveness (over 99 %), low cost, spontaneous reversibility and long-lasting usage. However, the side effects induced from the initial burst release of copper ions (Cu) hinder the continuation of the Cu-IUD made of Coarse-Grained Copper (CG Cu). We proposed to tailor the bio-corrosion behaviors of better control of Cu release via the addition of bioactive Mg into the Ultra-Fine Grained (UFG) Bulk Cu. Thus, UFG bulk Cu with 0.4 wt.% Mg was produced via equal-channel angular pressing. The microstructures of the UFG Cu-0.4Mg was observed using electron backscatter diffraction and transmission electron microscopy techniques. The in vitro long-term corrosion behaviors in simulated uterine fluid, cytotoxicity to four cell lines, in vivo biocompatibility and contraceptive efficacy were all studied on CG Cu, UFG Cu and UFG Cu-0.4Mg materials. The results demonstrate that both the ultrafine grains and the addition of bioactive Mg into Cu contribute to the suppression of the burst release of Cu in the initial stage and the maintenance of high level Cu in long-term release. Moreover, the UFG Cu-0.4Mg also exhibited much improved cell and tissue biocompatibility from both the in vitro and in vivo evaluations. Therefore, the contraceptive efficacy of UFG Cu-0.4Mg is still maintained as high as the CG Cu and UFG Cu while the side effects are significantly eased, suggesting the high potential of the UFG Cu-0.4Mg alloy as a new upgrading or alternative material for Cu-IUD. STATEMENT OF SIGNIFICANCE: The side effects from burst release of Cu at the initial implantation stage of Cu-containing intrauterine devices (Cu-IUD) is one of the main drawbacks of these devices. In this work, an ultra-fine-grained Cu (UFG Cu) alloyed with a low amount of bioactive Mg was used for a Cu-IUD. The UFG Cu-0.4Mg alloy exhibited suppressed burst release of Cu at initial implantation, while active Cu release for long-term usage was maintained, comparable to coarse-grained pure Cu. Furthermore, the UFG Cu-0.4Mg alloy displayed significantly improved biocompatibility with human uterus cells and a much decreased inflammatory response within the uterus. Therefore, the side effects from Cu-IUD were eased, while high antifertility efficacy of the UFG Cu-0.4Mg alloy was maintained. The UFG Cu-0.4Mg alloy is promising for Cu-IUD.
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http://dx.doi.org/10.1016/j.actbio.2021.04.037DOI Listing
April 2021

A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model.

Acta Biomater 2021 Apr 22. Epub 2021 Apr 22.

Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, China. Electronic address:

Osteochondral regeneration is an orchestrated process of inflammatory immunity, host cell response, and implant degradation in tissue engineering. Here, the effects of a platelet-rich plasma (PRP)-gelatin methacryloyl (GelMA) hydrogel scaffold fabricated using the digital micro-mirror device (DMD) technique for osteochondral repair were investigated in a rabbit model. GelMA hydrogels with different PRP concentrations were fabricated, and their roles in bone marrow mesenchymal stem cells (BMSCs) and macrophage polarization in vitro were investigated. The incorporation of 20% PRP into the hydrogel showed optimal effects on the proliferation, migration, and osteogenic and chondrogenic differentiation of BMSCs. The 20% PRP-GelMA (v/v) hydrogel also promoted M2 polarization with high expression of Arg1 and CD206. Compared to the 20% PRP group, the 50% PRP group showed similar biological roles in BMSCs but less extent of osteogenesis. In the vivo study, the 20% PRP-GelMA composite was used for osteochondral reconstruction and showed more cartilage and subchondral bone regeneration than that observed using the pure GelMA hydrogel. The PRP-GelMA group exhibited more M2 macrophage infiltration and less M1 macrophage presentation at three time points as compared to the nontreatment group. The expression of Arg1 in the PRP-GelMA group increased significantly at 6 weeks but decreased to a lower level at 12 weeks, while CD163 showed sustained high expression until 18 weeks. Our findings demonstrated that the 3D-printed PRP-GelMA composite could promote osteochondral repair through immune regulation by M2 polarization and could be a potential candidate for osteochondral tissue engineering. STATEMENT OF SIGNIFICANCE: PRP-GelMA hydrogels promoted the migration and osteogenic and chondrogenic differentiation of BMSCs. PRP-GelMA hydrogels participated in immune regulation and M1-to-M2 transition of macrophages. PRP-GelMA hydrogels coordinated and promoted several overlapping osteochondral repair events, including dynamic immune regulation, chemotaxis of MSCs, and osteochondral differentiation. PRP-GelMA hydrogels showed superior cartilage and subchondral bone repair properties.
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http://dx.doi.org/10.1016/j.actbio.2021.04.010DOI Listing
April 2021

Genome-wide identification of the GATA transcription factor family and their expression patterns under temperature and salt stress in Aspergillus oryzae.

AMB Express 2021 Apr 19;11(1):56. Epub 2021 Apr 19.

Jiangxi Key Laboratory of Bioprocess Engineering and Co-Innovation Center for In-Vitro Diagnostic Reagents and Devices of Jiangxi Province, College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang, 330013, China.

GATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillus oryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A. oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A. oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein-protein interaction network of A. oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A. oryzae.
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http://dx.doi.org/10.1186/s13568-021-01212-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055810PMC
April 2021

Noninvasive high-frequency oscillations riding spikes delineates epileptogenic sources.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213;

High-frequency oscillations (HFOs) are a promising biomarker for localizing epileptogenic brain and guiding successful neurosurgery. However, the utility and translation of noninvasive HFOs, although highly desirable, is impeded by the difficulty in differentiating pathological HFOs from nonepileptiform high-frequency activities and localizing the epileptic tissue using noninvasive scalp recordings, which are typically contaminated with high noise levels. Here, we show that the consistent concurrence of HFOs with epileptiform spikes (pHFOs) provides a tractable means to identify pathological HFOs automatically, and this in turn demarks an epileptiform spike subgroup with higher epileptic relevance than the other spikes in a cohort of 25 temporal epilepsy patients (including a total of 2,967 interictal spikes and 1,477 HFO events). We found significant morphological distinctions of HFOs and spikes in the presence/absence of this concurrent status. We also demonstrated that the proposed pHFO source imaging enhanced localization of epileptogenic tissue by 162% (∼5.36 mm) for concordance with surgical resection and by 186% (∼12.48 mm) with seizure-onset zone determined by invasive studies, compared to conventional spike imaging, and demonstrated superior congruence with the surgical outcomes. Strikingly, the performance of spike imaging was selectively boosted by the presence of spikes with pHFOs, especially in patients with multitype spikes. Our findings suggest that concurrent HFOs and spikes reciprocally discriminate pathological activities, providing a translational tool for noninvasive presurgical diagnosis and postsurgical evaluation in vulnerable patients.
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http://dx.doi.org/10.1073/pnas.2011130118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092606PMC
April 2021

Reduction-sensitive polymeric micelles as amplifying oxidative stress vehicles for enhanced antitumor therapy.

Colloids Surf B Biointerfaces 2021 Jul 1;203:111733. Epub 2021 Apr 1.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

Chemotherapy-photodynamic therapy (PDT)-based combination therapy is a currently frequently used means in cancer treatment that photosensitizer was able to generate reactive oxygen species (ROS) for improving chemotherapy, owing to the high oxidative stress of the tumor microenvironment (TME). Whereas, cancer cells were accustomed to oxidative stress by overexpression of antioxidant such as glutathione (GSH), which would consume the damage of ROS, as well as it could result in ineffective treatment. Herein, amplification of oxidative stress preferentially in tumor cells by consuming GSH or generating ROS is a reasonable treatment strategy to develop anticancer drugs. To achieve excellent therapeutic effects, we designed a GSH-scavenging and ROS-generating polymeric micelle mPEG-S-S-PCL-Por (MSLP) for amplifying oxidative stress and enhanced anticancer therapy. The amphiphilic polymer of methoxy poly(ethylene glycol) (mPEG)-S-S-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por) was self-assembled into polymeric micelles with the anticancer drug doxorubicin (DOX) for treatment and tracking via FRET. Spherical DOX/MSLP micelles with the average size of 88.76 ± 3.52 nm was procured with negatively charged surface, reduction sensitivity and high drug loading content (17.47 ± 1.53 %). The intracellular ROS detection showed that the MSLP could deplete glutathione and regenerate additional ROS. The cellular uptake of DOX/MSLP micelles was grabbed real-time monitoring by the Fluorescence resonance energy transfer (FRET) effect between DOX and MSLP. The reduction-sensitive polymeric micelles MSLP as amplifying oxidative stress vehicles combined chemotherapy and PDT exhibited significant antitumor activity both in vitro (IC50 = 0.041 μg/mL) and much better antitumor efficacy than that of mPEG-PCL-Por (MLP) micelles in vivo.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111733DOI Listing
July 2021

High-conductivity, stable Ag/cellulose paper prepared via in situ reduction of fractal-structured silver particles.

Carbohydr Polym 2021 Jun 12;262:117923. Epub 2021 Mar 12.

Shaanxi Provincial Key Laboratory of Papermaking Technology and Specialty Paper Development, National Demonstration Center for Experimental Light Chemistry Engineering Education, Key Laboratory of Paper Based Functional Materials of China National Light Industry, Shaanxi University of Science and Technology, Xian, 710021, China.

Flexible electronics products have attracted wide attention because of their excellent flexibility, conductivity and stability. In this study, the liquid phase reduction method was used to in situ reduce fractal-structured silver particles (FSSPs) on cellulose surface to prepare conductive paper with excellent conductivity, and good stability and flexibility. The experimental results show that when the mass ratio of silver to cellulose was 1.5:1, the sheet resistance of conductive paper is as low as 0.02 Ω·sq, and the conductivity reaches 1041.33 S cm, which shows excellent conductivity. In order to expand the application of conductive paper in the field of flexible wearable electronic products, the mechanical stability and oxidation resistance of conductive paper were tested. The results show that the conductive paper has good stability and is expected to replace the flexible electronics products made of plastic.
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http://dx.doi.org/10.1016/j.carbpol.2021.117923DOI Listing
June 2021

Continuous sensorimotor rhythm based brain computer interface learning in a large population.

Sci Data 2021 04 1;8(1):98. Epub 2021 Apr 1.

Carnegie Mellon University, Pittsburgh, PA, USA.

Brain computer interfaces (BCIs) are valuable tools that expand the nature of communication through bypassing traditional neuromuscular pathways. The non-invasive, intuitive, and continuous nature of sensorimotor rhythm (SMR) based BCIs enables individuals to control computers, robotic arms, wheel-chairs, and even drones by decoding motor imagination from electroencephalography (EEG). Large and uniform datasets are needed to design, evaluate, and improve the BCI algorithms. In this work, we release a large and longitudinal dataset collected during a study that examined how individuals learn to control SMR-BCIs. The dataset contains over 600 hours of EEG recordings collected during online and continuous BCI control from 62 healthy adults, (mostly) right hand dominant participants, across (up to) 11 training sessions per participant. The data record consists of 598 recording sessions, and over 250,000 trials of 4 different motor-imagery-based BCI tasks. The current dataset presents one of the largest and most complex SMR-BCI datasets publicly available to date and should be useful for the development of improved algorithms for BCI control.
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http://dx.doi.org/10.1038/s41597-021-00883-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016873PMC
April 2021

Performance of noninvasive prenatal screening in twin pregnancies: a retrospective study of 5469 twin pregnancies.

J Matern Fetal Neonatal Med 2021 Apr 1:1-9. Epub 2021 Apr 1.

Department of Obstetrics & Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

Objectives: To evaluate the performance of noninvasive prenatal screening (NIPS) for the fetal common aneuploidy screening in twin pregnancies.

Methods: The data of 5469 women with twin pregnancies were collected in this retrospective observational study between January 2017 and December 2018. Patients underwent NIPS as first-line screening or after standard serum screening for fetal aneuploidy. The performance of NIPS was examined, and a regression analysis was performed to investigate testing failure in cases of low fetal fraction.

Results: In this study, 2231 (40.8%) patients opted for NIPS as the primary prenatal screening test, and 3238 (59.2%) opted for serum screening, including 440 patients who opted for NIPS after serum screening. Among the 2671 pregnancies with available NIPS outcomes, 11 cases of aneuploidy were identified, seven of trisomy 21 and four of sex chromosome aneuploidy (SCA). The sensitivity and specificity for trisomy 21 were 100% (95% CI, 56.1-100.0%) and 100% (95% CI, 99.8-100.0%), respectively. The positive predictive value (PPV) for SCA was 40.0% (95% CI, 13.7-72.6%). No false negatives were found, with a negative predictive value (NPV) of 100% (95% CI, 99.8-100.0%) in total. In 32 pregnancies who failed NIPS test without available NIPS outcomes due to low fetal fraction, the regression analysis demonstrated that increasing BMI and assisted reproductive technology treatment were significant independent predictors.

Conclusions: NIPS is a high-performing routine primary prenatal screening test in twin pregnancies, with a high PPV and low false positive rate for detecting trisomy 21. It is also useful to identify common sex chromosome aneuploidies in twin pregnancies, with similar performance to that reported in singleton pregnancy.
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http://dx.doi.org/10.1080/14767058.2021.1903860DOI Listing
April 2021

Micro1278 Leads to Tumor Growth Arrest, Enhanced Sensitivity to Oxaliplatin and Vitamin D and Inhibits Metastasis KIF5B, CYP24A1, and BTG2, Respectively.

Front Oncol 2021 11;11:637878. Epub 2021 Mar 11.

Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.

Colorectal cancer (CRC) is the most common cancer type in the digestive tract. Chemotherapy drugs, such as oxaliplatin, are frequently administered to CRC patients diagnosed with advanced or metastatic disease. A better understanding of the molecular mechanism underlying CRC tumorigenesis and the identification of optimal biomarkers for assessing chemotherapy sensitivity are essential for the treatment of CRC. Various microRNAs, constituting class of non-coding RNAs with 20-22 nucleotides, have served as oncogenes or tumor suppressors in CRC. We analyzed miR-1278 expression in clinical samples by qRT-PCR. We then explored the role of miR-1278 in CRC growth and as well as sensitivity to oxaliplatin RNA-seq and gain- and loss-of-function assays. We found that miR-1278 was downregulated in CRC samples, correlating with advanced clinical stage, and overexpression of miR-1278 led to tumor growth arrest and increased sensitivity to oxaliplatin enhanced apoptosis and DNA damage. Suppression of KIF5B by miR-1278 through direct binding to its 3'UTR was the mechanism for the miR-1278-mediated effects in CRC, miR-1278 inhibits metastasis of CRC through upregulation of BTG2. Additionally, we also found that the expression of CYP24A1, the main enzyme determining the biological half-life of calcitriol, was significantly inhibited by miR-1278, according to data from clinical, RNA-seq and functional assays, which allowed miR-1278 to sensitize CRC cells to vitamin D. In summary, our data demonstrated that miR-1278 may serve as a potential tumor suppressor gene and biomarker for determining sensitivity to oxaliplatin and vitamin D in CRC.
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http://dx.doi.org/10.3389/fonc.2021.637878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006274PMC
March 2021

The herpesvirus accessory protein γ134.5 facilitates viral replication by disabling mitochondrial translocation of RIG-I.

PLoS Pathog 2021 Mar 26;17(3):e1009446. Epub 2021 Mar 26.

Department of Microbiology and Immunology University of Illinois College of Medicine, Chicago, Illinois, United States of America.

RIG-I and MDA5 are cytoplasmic RNA sensors that mediate cell intrinsic immunity against viral pathogens. While it has been well-established that RIG-I and MDA5 recognize RNA viruses, their interactive network with DNA viruses, including herpes simplex virus 1 (HSV-1), remains less clear. Using a combination of RNA-deep sequencing and genetic studies, we show that the γ134.5 gene product, a virus-encoded virulence factor, enables HSV growth by neutralization of RIG-I dependent restriction. When expressed in mammalian cells, HSV-1 γ134.5 targets RIG-I, which cripples cytosolic RNA sensing and subsequently suppresses antiviral gene expression. Rather than inhibition of RIG-I K63-linked ubiquitination, the γ134.5 protein precludes the assembly of RIG-I and cellular chaperone 14-3-3ε into an active complex for mitochondrial translocation. The γ134.5-mediated inhibition of RIG-I-14-3-3ε binding abrogates the access of RIG-I to mitochondrial antiviral-signaling protein (MAVS) and activation of interferon regulatory factor 3. As such, unlike wild type virus HSV-1, a recombinant HSV-1 in which γ134.5 is deleted elicits efficient cytokine induction and replicates poorly, while genetic ablation of RIG-I expression, but not of MDA5 expression, rescues viral growth. Collectively, these findings suggest that viral suppression of cytosolic RNA sensing is a key determinant in the evolutionary arms race of a large DNA virus and its host.
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http://dx.doi.org/10.1371/journal.ppat.1009446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996975PMC
March 2021