Publications by authors named "Lin Mei"

713 Publications

Piezo-photocatalytic effect mediating reactive oxygen species burst for cancer catalytic therapy.

Mater Horiz 2021 Aug 25;8(8):2273-2285. Epub 2021 Jun 25.

Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin 300072, China.

A piezo-photocatalytic therapy based on thermally treated natural sphalerite nanosheet (NSH700 NS) heterojunction was applied to efficiently induce intracellular ROS burst and apoptosis of cancer cells. Upon ultrasound and laser irradiation, the formation of a polarized electric field and band bending of NSH700 NSs allow the directional separation of charges both in the bulk and their interface, thereby minimizing the probability of charge recombination. The piezo-photocatalytic effect leads to an efficient catalytic performance, exhibiting high-performance superoxide radical (˙O) and hydroxyl radical (˙OH) generation and glutathione (GSH) depletion, which results in a intracellular ROS burst-triggered apoptosis of cancer cells both in vitro and in vivo.
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http://dx.doi.org/10.1039/d1mh00492aDOI Listing
August 2021

Neuregulin 1 and ErbB4 kinase actively regulate sharp wave ripples in the hippocampus.

J Neurosci 2021 Nov 29. Epub 2021 Nov 29.

Department of Neurosciences, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.

Sharp wave ripples (SW-Rs) in the hippocampus are synchronized bursts of hippocampal pyramidal neurons (PyNs), critical for spatial working memory. However, the molecular underpinnings of SW-Rs remain poorly understood. We show that SW-Rs in hippocampal slices from both male and female mice were suppressed by neuregulin 1 (NRG1), an epidermal growth factor whose expression is enhanced by neuronal activity. Pharmacological inhibition of ErbB4, a receptor tyrosine kinase for NRG1, increases SW-R occurrence rate in hippocampal slices. These results suggest an important role of NRG1-ErbB4 signaling in regulating SW-Rs. To further test this notion, we characterized SW-Rs in freely moving male mice, chemical genetic mutant mice, where ErbB4 can be specifically inhibited by the bulky inhibitor 1NMPP1. Remarkably, SW-R occurrence was increased by 1NMPP1. We found that 1NMPP1 increased the firing rate of PyN neurons, yet disrupted PyN neuron dynamics during SW-R events. Furthermore, 1NMPP1 increased SW-R occurrence during both non rapid eye movement sleep (NREM) states and wake states with a greater impact on SW-Rs during wake states. In accord, spatial working memory was attenuated in male mice. Together these results indicate that dynamic activity of ErbB4 kinase is critical to SW-Rs and spatial working memory. This study reveals a novel regulatory mechanism of SW-Rs and a novel function of the NRG1-ErbB4 signaling.SW-Rs are a hippocampal event, important for memory functioning. Yet the molecular pathways that regulate SW-Rs remain unclear. NRG1, previously known to be increased in PyN in an activity dependent manner, signals to its receptor, ErbB4 kinase, that is in important regulator of GABAergic transmission and long-term potentiation in the hippocampus. Our findings demonstrate that SW-Rs are regulated by this signaling pathway in a dynamic manner. Not only so, we show that this signaling pathway is dynamically needed for spatial working memory. These data suggest a molecular signaling pathway, NRG1-ErbB4 that regulates an important network event of the hippocampus, SW-Rs, that underlies memory functioning.
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http://dx.doi.org/10.1523/JNEUROSCI.1022-21.2021DOI Listing
November 2021

PEI-PEG-Coated Mesoporous Silica Nanoparticles Enhance the Antitumor Activity of Tanshinone IIA and Serve as a Gene Transfer Vector.

Evid Based Complement Alternat Med 2021 8;2021:6756763. Epub 2021 Nov 8.

Clinical Laboratory, Taizhou People's Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, Jiangsu 225300, China.

Tanshinone IIA (TanIIA) and gene therapy both hold promising potentials in hepatocellular carcinoma (HCC) treatment. However, low solubility and poor bioavailability of TanIIA limit its clinical application. Similarly, gene therapy with GPC3-shRNA, a type of short hairpin RNAs (shRNAs) capable of silencing the glypican-3 (GPC3) expression, is seriously limited due to its susceptibility to nuclease degradation and high off-target effects. In the present study, polyethyleneimine (PEI)-polyethylene glycol (PEG)-coated mesoporous silica nanoparticles (MSN-PEG) were used as a drug carrier. By encapsulating TanIIA into MSN-PEG, we synthesized MSN-TanIIA-PEG nanoparticles and observed the involved characteristics. This was followed by exploration of antitumor activity on the HepG2 cell lines . Meanwhile, in order to construct GPC3-shRNA plasmids, a shRNA sequence targeting GPC3 was synthesized and cloned into the pSLenti-U6 vector. Accordingly, the performance of MSN-PEG as a gene transfer carrier for GPC3-shRNA gene therapy of HCC was evaluated, including transfection efficiency and DNA binding biological characteristics. The results indicated successful encapsulation of TanIIA in MSN-PEG, which had satisfactory efficacy, favorable dispersity, suitable particle size, and sustained release effect. The anti-HCC effects of nano-TanIIA were greatly improved, which outperformed free-TanIIA in terms of proliferation and invasion inhibition, as well as apoptosis induction of HCC cells. As expected, MSN-PEG possessed excellent gene delivery capacity with good binding, release, and protection from RNase digestion. Using MSN-PEG as a gene carrier, the plasmids were successfully transfected into HepG2 cells, and both the mRNA and protein expressions of GPC3 were significantly downregulated. It was thus concluded that a sustained release TanIIA delivery system for HCC treatment was synthesized and that MSN-PEG could also serve as a gene transfer carrier for gene therapy. More interestingly, MSN-PEG may be a potential delivery platform that combines TanIIA and GPC3-shRNA together to enhance their synergistic effect.
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http://dx.doi.org/10.1155/2021/6756763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592735PMC
November 2021

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial.

J Immunother Cancer 2021 11;9(11)

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

Background: Toripalimab is a humanized immunoglobulin G monoclonal antibody against programmed death 1. We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC).

Methods: We conducted a single-arm, phase II trial with patients with rNPC who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate at 3 months post radiotherapy. The secondary endpoints included safety profiles, progression-free survival (PFS).

Results: Between May 2019 and January 2020, a total of 25 patients with rNPC were enrolled (18 men (72.0%) and 7 women (28.0%); median (IQR) age, 49.0 (43.5-52.5) years). With a median (IQR) follow-up duration of 14.6 months (13.1-16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month PFS was 91.8% (95% CI 91.7% to 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine kinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively.

Conclusions: Toripalimab combined with IMRT was tolerable and showed promising antitumor activity in patients with rNPC.

Trial Registration Number: NCT03854838.
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http://dx.doi.org/10.1136/jitc-2021-003290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593727PMC
November 2021

Parkinson's in the bone.

Cell Biosci 2021 Nov 5;11(1):190. Epub 2021 Nov 5.

Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.

Patients with Parkinson's disease (PD) exhibit systemic deficits, including arthritis and osteoporosis-like symptoms. However, the questions, how the deficits in periphery organs or tissues occur in PD patients, and what are the relationship (s) of the periphery tissue deficits with the brain pathology (e.g., dopamine neuron loss), are at the beginning stage to be investigated. Notice that both PD and osteoporosis are the products of a complex interaction of genetic and environmental risk factors. Genetic mutations in numerous genes have been identified in patients either with recessive or autosomal dominant PD. Most of these PD risk genes are ubiquitously expressed; and many of them are involved in regulation of bone metabolism. Here, we review the functions of the PD risk genes in regulating bone remodeling and homeostasis. The knowledge gaps in our understanding of the bone-to-brain axis in PD development are also outlined.
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http://dx.doi.org/10.1186/s13578-021-00702-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569842PMC
November 2021

[Effects of Human Immunodeficiency Virus-positive Mothers Receiving Antiretroviral Therapy to Prevent Mother-to-child Transmission on the Growth and Development of 18-month-old Children in Lingshan County of Guangxi].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Oct;43(5):743-748

Institute of AIDS Prevention and Control,Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention,Nanning 530028,China.

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(=33.520,<0.001).Conclusion After HIV-positive mothers in Lingshan County of Guangxi received ART for PMTCT,the incidence of growth stunting in 18-month-old children increased.
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http://dx.doi.org/10.3881/j.issn.1000-503X.14371DOI Listing
October 2021

CTNNA3 genetic polymorphism may be a new genetic signal of type 2 diabetes in the Chinese Han population: a case control study.

BMC Med Genomics 2021 10 30;14(1):257. Epub 2021 Oct 30.

Department of General Practice, Hainan General Hospital, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People's Republic of China.

Background: Type 2 Diabetes (T2D) is the result of a combination of genes and environment. The identified genetic loci can only explain part of T2D risk. Our study is aimed to explore the association between CTNNA3 single nucleotide polymorphisms (SNPs) and T2D risk.

Methods: We conducted a 'case-control' study among 1002 Chinese Han participants. Four candidate SNPs of CTNNA3 were selected (rs10822745 C/T, rs7920624 A/T, rs2441727 A/G, rs7914287 A/G), and logistic regression analysis was used to evaluate the association between candidate SNPs and T2D risk. We used single factor analysis of variance to analyze the differences of clinical characteristics among different genotypes. In this study, haplotype analysis was conducted by plink1.07 and Haploview software and linkage disequilibrium (LD) was calculated. The interaction of candidate SNPs in T2D risk was evaluated by multi-factor dimensionality reduction (MDR). Finally, we conducted a false-positive report probability (FPRP) analysis to detect whether the significant findings were just chance or noteworthy observations.

Results: The results showed that CTNNA3-rs7914287 was a risk factor for T2D ('T': OR = 1.33, p = 0.003; 'TT': OR = 2.21, p = 0.001; 'TT' (recessive): OR = 2.09, p = 0.001; Log-additive: OR = 1.34, p = 0.003). The results of subgroup analysis showed that rs7914287 was significantly associated with the increased risk of T2D among participants who were older than 60 years, males, smoking, drinking, or BMI > 24. We also found that rs2441727 was associated with reducing the T2D risk among participants who were older than 60 years, smoking, or drinking. In addition, rs7914287 was associated with T2D patients with no retinal degeneration; rs10822745 and rs7920624 were associated with the course of T2D patients. High density lipoprotein levels had significant differences under different genotypes of rs10822745. Under the different genotypes of rs7914287, the levels of aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase were also significantly different.

Conclusion: We found that CTNNA3 genetic polymorphisms can be used as a new genetic signal of T2D risk in Chinese Han population. Especially, CTNNA3-rs7914287 showed an outstanding and significant association with T2D risk in both overall analysis and subgroup analysis.
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http://dx.doi.org/10.1186/s12920-021-01105-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556947PMC
October 2021

Dysregulation of miR-638 in diabetic nephropathy and its role in inflammatory response.

Diabetol Metab Syndr 2021 Oct 29;13(1):122. Epub 2021 Oct 29.

Department of Nephrology, University of Chinese Academy of Sciences Shenzhen Hospital, 4221 Songbai Road, Shenzhen, 518000, Guangdong, China.

Background: MicroRNA (miRNA) can be used as a biomarker for the early diagnosis of diabetic nephropathy (DN). The purpose of this study was to evaluate the diagnostic value of miR-638 in DN and to analyse its regulatory effect on inflammation.

Methods: This retrospective study involved 98 subjects, including non-diabetic healthy controls (n = 30), patients with type 2 diabetes (T2DM, n = 36) without complications and patients with DN (n = 32). After the anthropometric and biochemical evaluation, serum miR-638 levels were assessed by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The levels of inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha [TNF-α]) were detected using enzyme-linked immunosorbent assay. The Spearman correlations were used to analyze the correlation between miR-638 and urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and inflammatory factors. Furthermore, the receiver operating characteristic (ROC) curve was used to measure the diagnostic value of miR-638 in DN. Human mesangial cells (HMCs) were treated with normal glucose (NG, 5.5 mM glucose), high glucose (HG, 30 mM glucose), or high osmotic pressure solution (HO, 5.5 mM glucose + 24.5 mM mannitol) in vitro to simulate the hyperglycamic state in vivo. Subsequently, the HMCs were transfected with miR-638 mimics to regulate the level of miR-638 in the cells and detect its regulation on cell inflammation and proliferation.

Results: Compared with healthy controls and patients with T2DM, serum miR-638 in patients with DN was significantly lower. The reduced miR-638 expression has a significant diagnostic value, which can significantly distinguish patients with DN from healthy controls or patients with T2DM. Inflammatory factors were significantly upregulated in patients with DN and negatively correlated with miR-638 levels. In addition, miR-638 was negatively correlated with UAE and positively correlated with eGFR. HG decreased the level of miR-638 and promoted the expression of inflammatory factors and proliferation in HMCs. However, miR-638 mimic significantly decreased the levels of inflammatory factors and inhibited the proliferative ability induced by HG.

Conclusions: Serum miR-638 expression was low in DN and can be a potentially valuable biomarker for DN. This miRNA seems to influence inflammatory responses and participate in the progression of DN by regulating proliferation.
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http://dx.doi.org/10.1186/s13098-021-00744-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555262PMC
October 2021

Molecular mechanism of Zopolrestat in improving airway inflammation induced by house dust mite in mice.

Minerva Surg 2021 Oct 25. Epub 2021 Oct 25.

Department of Respiratory and Critical Care Medicine, Wuhan Third Hospital, Wuhan, China.

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http://dx.doi.org/10.23736/S2724-5691.21.09114-0DOI Listing
October 2021

Enhancing the Health and Well-Being of People with Chronic Diseases: Assessment and Sustainable Development Planning for Therapeutic Landscapes after Urban Expansion.

J Healthc Eng 2021 8;2021:2828141. Epub 2021 Oct 8.

Faculty of Humanities and Arts, Macau University of Science and Technology, Macau 999078, China.

Under the influence of economic, environmental, and social structural changes, urban space expands and contracts to varying degrees and the everyday urban landscape changes in response. Over the past 20 years, a large number of cities in China have undergone a brief but rapid urban expansion and are moving toward shrinking cities. Most of these cities are now facing social problems such as an aging population and a high prevalence of chronic diseases. Therefore, the "therapeutic" role and impact of everyday landscapes in these cities need to be examined in the context of urban development processes through appropriate assessment methods. Therefore, this study applies the ANP-mV model to examine the therapeutic nature of everyday urban landscapes in different development periods, with the aim of enhancing the health and well-being of people with chronic diseases. Firstly, this study uses the city of Jinzhou in Northeast China as an example to develop a framework for assessing the therapeutic nature of everyday urban landscapes based on the health care needs of people with chronic diseases; secondly, it examines the therapeutic nature of the former Jinzhou Suburban Riverfront Forest Park as it has developed and evolved over the past 16 years; finally, it explores place-making and regeneration strategies for therapeutic landscapes from the perspectives of dynamic impact and sustainable development to enhance chronic illness patients' well-being. At the theoretical level, this study contributes by providing a methodology and research ideas for examining the "therapeutic" nature of everyday urban landscapes and proposing further development plans for renewal, constructing a framework for assessing therapeutic landscapes, and elucidating the relationship between networks of influence and the relative importance of various assessment dimensions/elements. At the practical application level, the contribution of this study is to provide local policymakers with a key decision basis for the future development planning of the East Lake Forest Park. The aim is to explore landscape creation and regeneration strategies for the East Lake Forest Park in the context of Jinzhou's progressive move toward a shrinking city, in order to sustain the well-being of the chronically ill.
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http://dx.doi.org/10.1155/2021/2828141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519705PMC
November 2021

Use of Immediate Postpartum Long-Acting Reversible Contraception Before and After a State Policy Mandated Inpatient Access.

Obstet Gynecol 2021 Nov;138(5):732-737

Obstetrics, Gynecology, & Women's Health Institute, and Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.

Objective: To assess the rate of immediate postpartum long-acting reversible contraceptive (LARC) use in a multihospital health care system 2 years before and after the policy was implemented, and to assess factors associated with LARC use and repeat pregnancy rates within 12 months after delivery.

Methods: We conducted a retrospective chart review of all patients giving birth at three Cleveland Clinic Ohio hospitals from July 1, 2015, to June 30, 2019. We reviewed the inpatient medication reconciliation to identify the LARC initiation rate. We compared all patients who received inpatient postpartum LARC to a 1:3 matched sample of patients who did not receive LARC, matched by delivery date and location, to identify patient characteristics associated with LARC use. The electronic medical record (Epic) was reviewed to identify new pregnancies occurring within 12 months postdelivery.

Results: We identified 17,848 deliveries prepolicy and 18,555 deliveries postpolicy. Immediate postpartum LARC was used by 0.5% (monthly range 0-2.1%) of patients prepolicy and 11.6% (monthly range 8.3-15.4%) of patients postpolicy. Levonorgestrel intrauterine devices (IUDs) were used by 56.5%, implants by 29.1%, and copper IUDs by 14.5% of LARC users. Characteristics associated with LARC use included younger age, public insurance, non-White race, Hispanic or Latina ethnicity, higher body mass index, sexually transmitted infection in pregnancy, and tobacco use. Long-acting reversible contraceptive users had a lower rate of repeat pregnancy at 12 months postpartum compared with the non-LARC group (1.9% vs 3.6%, P<.001).

Conclusion: Immediate postpartum LARC use increased after a state policy change mandated universal access and was associated with decreased pregnancy rates in the first year postdelivery.
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http://dx.doi.org/10.1097/AOG.0000000000004560DOI Listing
November 2021

Trehalose Phosphate Synthase Complex-Mediated Regulation of Trehalose 6-Phosphate Homeostasis Is Critical for Development and Pathogenesis in Magnaporthe oryzae.

mSystems 2021 Oct 5;6(5):e0046221. Epub 2021 Oct 5.

State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian University Key Laboratory for Plant-Microbe Interaction, College of Plant Protection, Fujian Agriculture and Forestry Universitygrid.256111.0, Fuzhou, China.

Trehalose biosynthesis pathway is a potential target for antifungal drug development, and trehalose 6-phosphate (T6P) accumulation is widely known to have toxic effects on cells. However, how organisms maintain a safe T6P level and cope with its cytotoxicity effects when accumulated have not been reported. Herein, we unveil the mechanism by which the rice blast fungus Magnaporthe oryzae avoids T6P accumulation and the genetic and physiological adjustments it undergoes to self-adjust the metabolite level when it is unavoidably accumulated. We found that T6P accumulation leads to defects in fugal development and pathogenicity. The accumulated T6P impairs cell wall assembly by disrupting actin organization. The disorganization of actin impairs the distribution of chitin synthases, thereby disrupting cell wall polymer distribution. Additionally, accumulation of T6P compromise energy metabolism. was able to overcome the effects of T6P accumulation by self-mutation of its gene at two different mutation sites. We further show that mutation of suppresses MoTps1 activity to reduce the intracellular level of T6P and partially restore Δ defects. Overall, our results provide insights into the cytotoxicity effects of T6P accumulation and uncover a spontaneous mutation strategy to rebalance accumulated T6P in . , the causative agent of the rice blast disease, threatens rice production worldwide. Our results revealed that T6P accumulation, caused by the disruption of , has toxic effects on fugal development and pathogenesis in . The accumulated T6P impairs the distribution of cell wall polymers via actin organization and therefore disrupts cell wall structure. uses a spontaneous mutation to restore T6P cytotoxicity. Seven spontaneous mutation sites were found, and a mutation in was further identified. The spontaneous mutation in can partially rescue Δ defects by suppressing MoTps1 activity to alleviate T6P cytotoxicity. This study provides clear evidence for better understanding of T6P cytotoxicity and how the fungus protects itself from T6P's toxic effects when it has accumulated to severely high levels.
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http://dx.doi.org/10.1128/mSystems.00462-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547450PMC
October 2021

Long Noncoding RNAs Regulate the Radioresistance of Breast Cancer.

Anal Cell Pathol (Amst) 2021 20;2021:9005073. Epub 2021 Sep 20.

Research Center of Clinical Medicine, Taizhou People's Hospital (the Affiliated Hospital 5 of Nantong University), Taizhou, 225300 Jiangsu Province, China.

Breast cancer (BRCA) has severely threatened women's health worldwide. Radiotherapy is a treatment for BRCA, which applies high doses of ionizing radiation to induce cancer cell death and reduce disease recurrence. Radioresistance is one of the most important elements that affect the therapeutic efficacy of radiotherapy. Long noncoding RNAs (lncRNAs) are suggested to dominate crucial roles in regulating the biological behavior of BRCA. Currently, some studies indicate that overexpression or inhibition of lncRNAs can greatly alter the radioresistance of BRCA. In this review, we summarized the knowledge on the classification and function of lncRNAs and the molecular mechanism of BRCA radioresistance, listed lncRNAs related to the BRCA radioresistance, highlighted their underlying mechanisms, and discussed the potential application of these lncRNAs in regulating BRCA radioresistance.
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http://dx.doi.org/10.1155/2021/9005073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478560PMC
September 2021

The effect of estrogen therapy on spermatogenesis in transgender women.

F S Rep 2021 Sep 11;2(3):347-351. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Cleveland Clinic Foundation, Cleveland, Ohio.

Objective: To describe the histopathologic parameters of orchiectomy specimens obtained after gender-affirming surgery from transgender women who used gender-affirming hormone therapy (GAHT), which included estrogen and spironolactone. Our hypothesis was that an increasing duration of GAHT affects testicular health.

Design: Retrospective cohort study.

Setting: Tertiary referral center.

Patients: All transgender women (individuals assigned male at birth who identified as female) who underwent orchiectomy with or without vaginoplasty between December 2015 and March 2020.

Interventions: GAHT (estrogen and spironolactone) in the setting of patients with orchiectomy with or without vaginoplasty.

Main Outcome Measures: Demographic and perioperative data and pathology records were reviewed. The following pathology parameters were recorded: testicular volume, testicular weight, presence of spermatogenesis (active vs. reduced), maturation arrest, testicular atrophy, hyalinization, scarring/fibrosis, and Sertoli cell and Leydig cell phenotypes. The patients were grouped into one of three categories describing the duration of GAHT use: 0-36 months, 37-60 months, and >60 months years. Descriptive statistics were performed and comparisons between outcomes (demographic data and pathology parameters) were made among the GAHT groups.

Results: Eighty-five (N = 85) patients underwent orchiectomy during the study period with 85.9% (n = 73) undergoing concurrent vaginoplasty. The mean (SD) age and body mass index of the cohort were 39 ±16 years and 28.4 ± 5.4 kg/m, respectively. In addition, although this was not statistically significant, patients in the 37-60 and >60-month groups were more likely to smoke marijuana than those in the 0-36-month group (26.3% and 21.2% vs. 4.2%, respectively). Mean testicular weight and volume across the cohort were 60.1 ± 24.9 grams and 65.5 ± 41.1 cm, respectively. Spermatogenesis was present in 28.2% (n = 24) of specimens with active spermatogenesis noted in 8.2% (n = 7). Hyalinization, scarring/fibrosis, and atrophy were present in 28.2% (n = 24), 20.0% (n = 17), and 25.9% (n = 22) of specimens, respectively. There were no differences in pathology parameters across the GAHT groups. Testicular weight and volume were not associated with any differences in pathology parameters. Additionally, age was not associated with testicular weight, volume, or pathology parameters with the exception of the following: when patients were categorized as either ≤40 years of age (n = 48) vs. > 40 years of age (n = 37), patients who were older were more likely to have hyalinization (43.2% vs. 16.7%) as well as atrophy (40.5% vs. 14.6%).

Conclusions: The duration of GAHT use was not associated with any differences in orchiectomy pathology parameters in patients undergoing gender-affirming surgery, and some patients may still have some spermatogenesis based on the parameters observed in this study.
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http://dx.doi.org/10.1016/j.xfre.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441557PMC
September 2021

Recent advances in fecal gene detection for colorectal cancer diagnosis.

Biomark Med 2021 Oct 21;15(14):1299-1308. Epub 2021 Sep 21.

Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China.

There has been a gradual increase in the incidence of colorectal cancer (CRC) in recent years. Most patients lack obvious early symptoms, but are commonly in mid and advanced stages when the symptoms become evident, with rather high mortalities. Early diagnosis, treatment and recurrence monitoring are crucial to improving the recovery rate of CRC. Studies have shown that tumor-related genes can be detected in the feces of CRC patients. Owing to non-invasiveness, convenient sampling and continuous dynamic monitoring, fecal gene detection may be applicable to CRC screening, diagnosis, prognostic assessment and recurrence monitoring. Herein, we review the research advances in fecal gene detection for CRC diagnosis.
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http://dx.doi.org/10.2217/bmm-2021-0269DOI Listing
October 2021

Preliminary study of genome-wide association identified novel susceptibility genes for thyroid-related hormones in Chinese population.

Genes Genomics 2021 Sep 17. Epub 2021 Sep 17.

Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People's Republic of China.

Background: Thyroid hormones are critical regulators of metabolism, development and growth in mammals. However, the genetic association of thyroid-related hormones in the Chinese Han population is not fully understood.

Objective: We aimed to identify the genetic loci associated with circulating thyroid-related hormones concentrations in the healthy Chinese Han population.

Methods: Genotyping was performed in 124 individuals using Applied Biosystems™ Axiom™ PMDA, and 796,288 single nucleotide polymorphisms (SNPs) were available for the GWAS analysis. For replication, eleven SNPs were selected as candidate loci for genotyping by Agena MassARRAY platform in additional samples (313 subjects). The values of p < 5 × 10 suggest a suggestively significant genome-wide association with circulating thyroid-related hormones concentrations.

Results: We identified that rs11178277 (PTPRB, p = 4.88 × 10) and rs7320337 (LMO7DN-KCTD12, p = 1.22 × 10) were associated with serum FT3 level. Three SNPs (rs4850041 in LOC105373394-LINC01249: p = 3.55 × 10, rs6867291 in LINC02208: p = 2.40 × 10 and rs79508321 in WWOX: p = 3.35 × 10) were related to circulating T3 level. Rs12474167 (LOC105373394-LINC01249, p = 1.65 × 10) and rs1864553 (IWS1, p = 2.00 × 10) were associated with circulating T4 concentration. The association with TGA concentration was for rs17163542 in DISP1 (p = 3.46 × 10) and rs12601151 in NOG-C17orf67 (p = 2.72 × 10). Two genome-level significant SNPs (rs2114707 in LINC01314, p = 1.69 × 10 and rs12601151, p = 1.41 × 10) associated with serum TMA concentration were identified. Moreover, rs6083269 (CST1-CST2, p = 3.36 × 10) was a significant locus for circulating TSH level. In replication, rs12601151 in NOG-C17orf67 was still associated with serum TGA level (p = 0.012).

Conclusions: The GWAS reported 11 new suggestively significant loci associated with circulating thyroid-related hormones levels among the Chinese Han population. These findings represented suggestively biological candidates for circulating thyroid-related hormones levels and provided new insights into the mechanisms of regulating serum TGA concentration.
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http://dx.doi.org/10.1007/s13258-021-01165-1DOI Listing
September 2021

A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors.

Front Oncol 2021 27;11:667847. Epub 2021 Aug 27.

CAMC Cancer Center, Charleston, WV, United States.

Introduction: Brain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed.

Methods: Variables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified.

Results: A total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85-0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 . 8.2 months; HR: 0.86; 95% CI: 0.82-0.90), TNBC (23.9 . 11.6 months; HR: 0.87; 95% CI: 0.82-0.92), and melanoma (27.6 . 16.8 months; HR: 0.80; 95% CI: 0.73-0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 . 14.0 months; HR: 0.96; 95% CI: 0.86-1.10).

Conclusions: Overall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted.
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http://dx.doi.org/10.3389/fonc.2021.667847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429930PMC
August 2021

Charge-reversal biodegradable MSNs for tumor synergetic chemo/photothermal and visualized therapy.

J Control Release 2021 10 10;338:719-730. Epub 2021 Sep 10.

Institute of Pharmaceutics, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China. Electronic address:

Given the difficulties of biodegradation of mesoporous silica nanoparticles (NPs), enrichment and penetration of tumor sites, and real-time monitoring of the treatment process, we developed a kind of mannose-doping doxorubicin-loading mesoporous silica nanoparticle (MSN-Man-DOX) and coated by polydopamine-Gd (PDAGd) metal-phenolic networks, as well as modified by poly (2-Ethyl-2-Oxazoline) (PEOz), constructing a novel nanomedicine [email protected] Its pH-responsive charge reversal, photothermal, biodegradation, drug release, and magnetic resonance imaging (MRI) properties were evaluated in vitro. Cellular uptake, tumor penetration, lysosomal escape properties, as well as cell safety and toxicity of the nanoplatform were investigated through cell experiments. Finally, the MRI, organ distribution, photothermal condition, and comprehensive anti-tumor therapy in vivo were evaluated comprehensively through animal experiments. Research results showed that [email protected] had outstanding tumor enrichment and penetration abilities, which can produce excellent treatment effects through the synergistic effect of chemotherapy and photothermal therapy (PTT) with the function of magnetic resonance imaging contrast agent for disease monitoring. Besides, after finishing the therapeutic effect [email protected] can be biodegraded, so it had a good prospect of clinical application.
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http://dx.doi.org/10.1016/j.jconrel.2021.09.005DOI Listing
October 2021

The impact of induction chemotherapy on long-term quality of life in patients with locoregionally advanced nasopharyngeal carcinoma: Outcomes from a randomised phase 3 trial.

Oral Oncol 2021 10 20;121:105494. Epub 2021 Aug 20.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort.

Methods: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period.

Results: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT.

Conclusion: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105494DOI Listing
October 2021

Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population.

Biol Trace Elem Res 2021 Aug 21. Epub 2021 Aug 21.

Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou #19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People's Republic of China.

Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in BCHE-LOC105374194, DTX2P1-UPK3BP1-PMS2P11, VAT1L, LINC00908-LINC00683, LINC01310-NONE, and rs6747410 in VWA3B were identified to be associated with serum Cu element concentration (p < 5 × 10). ADAMTSL1 rs17229526 (p = 4.96 × 10) was significantly associated with serum Zn element levels. Genetic loci in LRP1B, PIGZ-MELTF, LINC01365-LINC02502, and HAPLN3 were related to serum Ca element levels (p < 5 ×1 0). Three SNPs in ALPK1, ASAP1-ADCY8 and IER3IP1-SKOR2 also achieved a significant association with Mg element levels (p < 5 × 10). TACSTD2-MYSM1, LRP1B, and ASAP1-ADCY8 showed suggestive associations with serum Fe element levels (p < 5 × 10). Moreover, the two most significant SNPs associated with Pb were rs304234 in CADPS-LINC00698 (p = 2.47 × 10) and rs12666460 in LOC101928211-GPR37 (p = 1.81 × 10). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.
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http://dx.doi.org/10.1007/s12011-021-02854-4DOI Listing
August 2021

Hydrogel/nanoadjuvant-mediated combined cell vaccines for cancer immunotherapy.

Acta Biomater 2021 10 15;133:257-267. Epub 2021 Aug 15.

Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China. Electronic address:

Combined cell vaccines of tumor whole cells and dendritic cells (DCs) provide an effective individualized immunotherapy for malignant tumors. We propose an innovative strategy termed "biomaterial-mediated combined cell vaccines for immunotherapy," which combines tumor cell and DC vaccines with a cyclodextrin-polyethylene glycol hydrogel and a cytosine-phosphate-guanine (CpG) nanoadjuvant. The nanoadjuvant promotes antigen presentation and amplifies immune-eliciting potency by co-delivery of antigens and adjuvants. The hydrogel scaffold provides a better growth microenvironment for injected exogenous DCs and recruits endogenous DCs to maintain their viability for synergistic effect. The results indicated that, relative to live tumor cells, the immunogenically dying tumor cells activated DC maturation effectively with the auxiliary effect of immune adjuvant CpG nanoparticles. The increased T cell percentage, proliferation ability, cytokine secretion, and cytotoxic effect revealed the enhanced immunogenicity of the combined cell vaccines. The combined hydrogel/nanoadjuvant system showed the best efficiency in inhibiting tumor growth. Moreover, vaccination with a single dose of hydrogel-based combined vaccines significantly delayed the development of tumors. The biomaterial-mediated combined cell vaccines remarkably increased the infiltration of effector T cells, alleviated the intratumoral immunosuppressive microenvironment, and maximized the immune effect of the vaccines, thus improving cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cell-based vaccines, including tumor whole-cell vaccine or DC vaccine, have attracted wide attention as an effective method for cancer immunotherapy. However, it is difficult to gain satisfactory outcomes in clinical trials because of the low immunogenicity of tumor whole cell vaccine and the short-term survival of transferred DC vaccine. Therefore, improving the ability of cell-based vaccines to induce a strong and durable immune response is the primary objective for vaccine development. Biomaterial-mediated combined cell vaccines is an innovative strategy for cancer immunotherapy. The combined hydrogel/ nanoadjuvant system comprises immunogenically dying tumor cells, DCs, and nanoadjuvants. Nanoadjuvant-loaded immunogenically dying tumor cells can induce efficient immune response as the tumor cell vaccine. The hydrogel-based combined tumor cell/DC vaccine could be used for individualized immunotherapy.
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http://dx.doi.org/10.1016/j.actbio.2021.08.014DOI Listing
October 2021

GDF11 protects against glucotoxicity-induced mice retinal microvascular endothelial cell dysfunction and diabetic retinopathy disease.

Mol Cell Endocrinol 2021 Nov 12;537:111422. Epub 2021 Aug 12.

Department of Endocrinology, Nanhai District People's Hospital of Foshan, Foping Road 40, Foshan, 528200, Guangdong Province, China.

Growth differentiation factor 11 (GDF11) has been implicated in the regulation of embryonic development and age-related dysfunction, including the regulation of retinal progenitor cells. However, little is known about the functions of GDF11 in diabetic retinopathy. In this study, we demonstrated that GDF11 treatment improved diabetes-induced retinal cell death, capillary degeneration, pericyte loss, inflammation, and blood-retinal barrier breakdown in mice. Treatment of isolated mouse retinal microvascular endothelial cells with recombinant GDF11 in vitro attenuated glucotoxicity-induced retinal endothelial apoptosis and the inflammatory response. The protective mechanisms exerted are associated with TGF-β/Smad2, PI3k-Akt-FoxO1 activation,and NF-κB pathway inhibition. This study indicated that GDF11 is a novel therapeutic target for diabetic retinopathy.
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http://dx.doi.org/10.1016/j.mce.2021.111422DOI Listing
November 2021

Arsenene-mediated multiple independently targeted reactive oxygen species burst for cancer therapy.

Nat Commun 2021 08 6;12(1):4777. Epub 2021 Aug 6.

Center for Nanomedicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/AsO NSs) with type II heterojunction are fabricated with efficient ·O and O production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of AsO with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O from HO, but also inactivates main anti-oxidants to cut off the "retreat routes" of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/[email protected]@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/[email protected]@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy.
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http://dx.doi.org/10.1038/s41467-021-24961-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346549PMC
August 2021

Mediastinal Low-Grade Fibromyxoid Sarcoma With FUS-CREB3L2 Gene Fusion.

Cureus 2021 Jun 11;13(6):e15606. Epub 2021 Jun 11.

Oncology, Charleston Area Medical Center (CAMC), Charleston, USA.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare subclass of sarcoma. Histologically, they are characterized by bland-appearing fibroblastic spindle cells and are similar to sclerosing epithelioid fibrosarcoma (SEF) subtype. The standard treatment of this aggressive tumor subtype is surgical removal with wide excision in conjunction with doxorubicin chemotherapy. Due to the rarity of this disease, effective systemic therapies are lacking and patient outcomes remain poor. Herein, we report on a 50-year-old male who presented with severe shortness of breath. Subsequent imaging revealed pericardial effusion and large mediastinal mass consistent with locally advanced disease. Fine needle biopsy demonstrated malignant, Ewing-like round tumor cells. Further genetic analysis affirmed the presence of FUS-CREB3L2 gene fusion. The patient was treated with doxorubicin and survival time from the initial presentation was five months. To date, there are limited reports of this disease. Few targeted therapies or immunotherapies for LGFMS exist, and a dire need for new therapy development remains.
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http://dx.doi.org/10.7759/cureus.15606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273027PMC
June 2021

Electrochemical-induced hydroxylation of aryl halides in the presence of EtN in water.

Org Biomol Chem 2021 Jul;19(29):6417-6421

Faculty of Material and Chemical Engineering, Yibin University, Yibin 644000, China and Institute of Materia Medica, School of Pharmacy, Fujian Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou 350122, China.

A thorough study of mild and environmentally friendly electrochemical-induced hydroxylation of aryl halides without a catalyst is presented. The best protocol consists of hydroxylation of different aryl iodides and aryl bromides by water solution in the presence of Et3N under air, affording the target phenols in good isolated yields. Moreover, aryl chlorides were successfully employed as substrates. This methodology also provides a direct pathway for the formation of deoxyphomalone, which displayed a significant anti-proliferation effect.
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http://dx.doi.org/10.1039/d1ob00931aDOI Listing
July 2021

Characterization of LRP4/Agrin Antibodies From a Patient With Myasthenia Gravis.

Neurology 2021 09 7;97(10):e975-e987. Epub 2021 Jul 7.

From the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.

Background And Objective: To determine whether human anti-LRP4/agrin antibodies are pathogenic in mice and to investigate underpinning pathogenic mechanisms.

Methods: Immunoglobulin (Ig) was purified from a patient with myasthenia gravis (MG) with anti-LRP4/agrin antibodies and transferred to mice. Mice were characterized for body weight, muscle strength, twitch and tetanic force, neuromuscular junction (NMJ) functions including compound muscle action potential (CMAP) and endplate potentials, and NMJ structure. Effects of the antibodies on agrin-elicited muscle-specific tyrosine kinase (MuSK) activation and AChR clustering were studied and the epitopes of these antibodies were identified.

Results: Patient Ig-injected mice had MG symptoms, including weight loss and muscle weakness. Decreased CMAPs, reduced twitch and tetanus force, compromised neuromuscular transmission, and NMJ fragmentation and distortion were detected in patient Ig-injected mice. Patient Ig inhibited agrin-elicited MuSK activation and AChR clustering. The patient Ig recognized the β3 domain of LRP4 and the C-terminus of agrin and reduced agrin-enhanced LRP4-MuSK interaction.

Discussion: Anti-LRP4/agrin antibodies in the patient with MG is pathogenic. It impairs the NMJ by interrupting agrin-dependent LRP4-MuSK interaction.
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http://dx.doi.org/10.1212/WNL.0000000000012463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448554PMC
September 2021

LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease.

BMC Pulm Med 2021 Jul 7;21(1):213. Epub 2021 Jul 7.

Department of General Practice, Hainan General Hospital, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People's Republic of China.

Objective: Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility.

Methods: Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility.

Results: LINC01414 rs699467 (OR = 0.73, 95% CI 0.56-0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31-0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31-6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008).

Conclusion: Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.
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http://dx.doi.org/10.1186/s12890-021-01579-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261955PMC
July 2021

Correction to: Advances in PSMA-targeted therapy for prostate cancer.

Prostate Cancer Prostatic Dis 2021 Jul 6. Epub 2021 Jul 6.

Taizhou People's Hospital Affiliated to Nantong University, Taizhou, Jiangsu, China.

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http://dx.doi.org/10.1038/s41391-021-00421-5DOI Listing
July 2021

The Emergence and Evolution of Borophene.

Adv Sci (Weinh) 2021 06 2;8(12):2001801. Epub 2021 May 2.

School of Pharmaceutical Sciences (Shenzhen) Sun Yat-sen University Guangzhou 510275 P. R. China.

Neighboring carbon and sandwiched between non-metals and metals in the periodic table of the elements, boron is one of the most chemically and physically versatile elements, and can be manipulated to form dimensionally low planar structures (borophene) with intriguing properties. Herein, the theoretical research and experimental developments in the synthesis of borophene, as well as its excellent properties and application in many fields, are reviewed. The decade-long effort toward understanding the size-dependent structures of boron clusters and the theory-directed synthesis of borophene, including bottom-up approaches based on different foundations, as well as up-down approaches with different exfoliation modes, and the key factors influencing the synthetic effects, are comprehensively summarized. Owing to its excellent chemical, electronic, mechanical, and thermal properties, borophene has shown great promise in supercapacitor, battery, hydrogen-storage, and biomedical applications. Furthermore, borophene nanoplatforms used in various biomedical applications, such as bioimaging, drug delivery, and photonic therapy, are highlighted. Finally, research progress, challenges, and perspectives for the future development of borophene in large-scale production and other prospective applications are discussed.
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http://dx.doi.org/10.1002/advs.202001801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224432PMC
June 2021
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