Publications by authors named "Ying Sun"

1,931 Publications

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Total synthesis of crotophorbolone.

Chem Sci 2020 Jun 19;11(27):7177-7181. Epub 2020 Jun 19.

Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University 29 Wangjiang Rd. Chengdu Sichuan 610064 China

As a natural diterpenoid, crotophorbolone possesses a challenging ,-5/7/6 framework decorated with six contiguous stereogenic centers and is structurally and biogenetically related to tigliane-type diterpenoids with intriguing bioactivities such as phorbol and prostratin. Based on the convergent strategy, we completed an eighteen-step total synthesis of crotophorbolone starting from (-)-carvone and (+)-dimethyl-2,3--isopropylidene-l-tartrate. The key elements of the synthesis involve expedient installation of the six-membered ring and the five-membered ring with multiple functional groups at an early stage, cyclization of the seven-membered ring through alkenylation of the ketone between the five-membered ring and the six-membered ring, functional group-sensitive ring-closing metathesis and final selective introduction of hydroxyls at C and C.
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http://dx.doi.org/10.1039/d0sc02829kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159391PMC
June 2020

Colorimetry and SERS dual-mode sensing of serotonin based on functionalized gold nanoparticles.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 5;261:120057. Epub 2021 Jun 5.

College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China. Electronic address:

In this study, we reported a colorimetry and SERS dual-mode sensing of serotonin (5-HT) based on functionalized gold nanoparticles (AuNPs). Based on the amino and hydroxyl groups in 5-HT can react with dithiobis succinimidyl propionate (DSP) and N-acetyl-L-cysteine (NALC) respectively, we synthesized two kinds of functionalized AuNPs (DSP-AuNPs and NALC-AuNPs). A double interaction between functionalized nanoparticles and the hydroxyl and the amino group of serotonin led to interparticle-crosslinking aggregation. The aggregation of the two functionalized AuNPs can cause the plasmon coupling of AuNPs resulting in a color change visible to the naked eye and the enlargement of SERS "hot spot" area and the enhancement of SERS signal. Furthermore, two kinds of functionalized AuNPs can specifically recognize 5-HT and effectively reduce the interference of biomolecules with similar structure to 5-HT in the experiment. This dual-mode system has the advantages of low detection limit, high sensitivity and good selectivity, and the detection limit is 0.15 nmol L. Besides, the system was applied to the determination of 5-HT content in human serum, and the relative standard deviation (RSD) was lower than 3.75%, which indicated that the system had a good application prospect in the determination of biological samples.
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http://dx.doi.org/10.1016/j.saa.2021.120057DOI Listing
June 2021

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

Lancet 2021 Jun 4. Epub 2021 Jun 4.

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

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.

Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.

Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.

Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.

Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(21)01123-5DOI Listing
June 2021

Monitoring patient flow in a hospital emergency department: ARMA-based nonparametric GLRT scheme.

Health Informatics J 2021 Apr-Jun;27(2):14604582211021649

Department of Electrical Engineering, University of Sharjah, United Arab Emirates.

Overcrowding in emergency departments (EDs) is a primary concern for hospital administration. They aim to efficiently manage patient demands and reducing stress in the ED. Detection of abnormal ED demands (patient flows) in hospital systems aids ED managers to obtain appropriate decisions by optimally allocating the available resources following patient attendance. This paper presents a monitoring strategy that provides an early alert in an ED when an abnormally high patient influx occurs. Anomaly detection using this strategy involves the amalgamation of autoregressive-moving-average (ARMA) time series models with the generalized likelihood ratio (GLR) chart. A nonparametric procedure based on kernel density estimation is employed to determine the detection threshold of the ARMA-GLR chart. The developed ARMA-based GLR has been validated through practical data from the ED at Lille Hospital, France. Then, the ARMA-based GLR method's performance was compared to that of other commonly used charts, including a Shewhart chart and an exponentially weighted moving average chart; it proved more accurate.
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http://dx.doi.org/10.1177/14604582211021649DOI Listing
June 2021

Oral Microbiome Characteristics in Patients With Autoimmune Hepatitis.

Front Cell Infect Microbiol 2021 19;11:656674. Epub 2021 May 19.

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Autoimmune hepatitis (AIH) is a common cause of liver cirrhosis. To identify the characteristics of the oral microbiome in patients with AIH, we collected 204 saliva samples including 68 AIH patients and 136 healthy controls and performed microbial MiSeq sequencing after screening. All samples were randomly divided into discovery cohorts (46 AIH and 92 HCs) and validation cohorts (22 AIH and 44 HCs). Moreover, we collected samples of 12 AIH patients from Hangzhou for cross-regional validation. We described the oral microbiome characteristics of AIH patients and established a diagnostic model. In the AIH group, the oral microbiome diversity was significantly increased. The microbial communities remarkably differed between the two groups. Seven genera, mainly and , were dominant in the HC group, while 51 genera, and , were enriched in the AIH group. Notably, we found 23 gene functions, including Membrane Transport, Carbohydrate Metabolism, and Glycerolipid metabolism that were dominant in AIH and 31 gene functions that prevailed in HCs. We further investigated the correlation between the oral microbiome and clinical parameters. The optimal 5 microbial markers were figured out through a random forest model, and the distinguishing potential achieved 99.88% between 46 AIH and 92 HCs in the discovery cohort and 100% in the validation cohort. Importantly, the distinguishing potential reached 95.55% in the cross-regional validation cohort. In conclusion, this study is the first to characterize the oral microbiome in AIH patients and to report the successful establishment of a diagnostic model and the cross-regional validation of microbial markers for AIH. Importantly, oral microbiota-targeted biomarkers may be able to serve as powerful and noninvasive diagnostic tools for AIH.
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http://dx.doi.org/10.3389/fcimb.2021.656674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170700PMC
May 2021

Primary Intracranial Leiomyosarcoma Secondary to Glioblastoma: Case Report and Literature Review.

Front Oncol 2021 20;11:642683. Epub 2021 May 20.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.

Background: Leiomyosarcoma is a highly malignant soft-tissue sarcoma with a poor prognosis. In recent years, treatment for leiomyosarcoma has not shown much progress. Primary intracranial leiomyosarcoma (PILMS) is a much rarer type of neoplasm, which occurs more frequently in immunocompromised patients. PILMS cases reported in the literature are scarce and treatment strategy and prognosis are still under debate. In this study, a case of PILMS secondary to the total resection of giant cell glioblastoma is reported.

Case Description: A 38-year-old male was hospitalized with a three-month history of a temporal opisthotic bump. His medical history included a total resection of a tumor located in the right temporal lobe performed 4 years earlier. Pathological examination led to a diagnosis of giant cell glioblastoma, and the patient underwent postoperative chemotherapy with temozolomide for 6 weeks plus simultaneous radiotherapy with 63.66 Gary. Four years later, during regular follow-up, a preoperative MRI brain scan resulted in a well-defined signal pointing out two nodule-like features located at the right temporal lobe and subcutaneous soft tissue, respectively, and near the area where the previous giant cell glioblastoma was located. The mass was completely removed by a transtemporal approach and postoperative pathology revealed that the mass was a leiomyosarcoma. The patient underwent postoperative radiotherapy and no recurrence occurred until now.

Conclusions: To date, research on soft-tissue sarcoma, especially PILMS, has not made much progress, and a limited number of studies have provided few details on the management of PILMS. The treatment of choice for PILMS is aggressive multimodal treatment based on total tumor resection and radiotherapy. Moreover, systemic treatment with chemotherapy and targeted therapy, such as olaratumab, as well as further research still needs to be performed as many questions are left unanswered. To our knowledge, this is the first report on a case of PILMS secondary to glioblastoma, which might serve as a potential reference for clinicians and clinical studies.
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http://dx.doi.org/10.3389/fonc.2021.642683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173044PMC
May 2021

Effects of coexistence of tetracycline, copper and microplastics on the fate of antibiotic resistance genes in manured soil.

Sci Total Environ 2021 May 29;790:148087. Epub 2021 May 29.

College of Environmental Science and Engineering, State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China.

The coexistence of antibiotics, heavy metals and microplastics is becoming commonplace and may affect antibiotic resistance in manured soil. The current understanding of the role of microplastics in soil with combined pollution of antibiotics, heavy metals and antibiotic resistance genes (ARGs) is limited. Here, the effects of the coexistence of tetracycline (TC), Cu and environmental microplastics (EM) on the fate of nine ARGs and three heavy metal resistance genes in agricultural soil were investigated by batch and microcosm experiments. EM were obtained by exposing virgin microplastics to soil environments for 80 days, which exhibited higher adsorption affinity for Cu and TC than soil particles and virgin microplastics. 1% EM in soil increased bioavailable concentrations of TC and Cu by 79-138% and 88-135%, respectively, and decreased TC dissipation from 11.79 mg kg to 3.08 mg kg. Correspondingly, the total relative abundances of target ARGs increased by 219-348%. The significant correlations of tetG, tetB, tetQ, sul2, sul1 and intl1 with bioavailable fractions of TC and Cu in soil environments were revealed by network analysis. Moreover, scanning electron micrographs showed the special plastisphere around EM. Attributed to the biofilm generation and higher pollutant accumulation in the plastisphere, EM could be the source of antibiotic-resistant bacteria and ARGs in soil environments. Structure equation models further identified that indirect effects of EM acted a major role in the propagation of ARGs by altering soil properties, soil microbial diversity and intl1 abundance. This study revealed that EM could increase the stimulative effects of Cu and TC on antibiotic resistance and magnify the environmental risk of manure application in soil environments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148087DOI Listing
May 2021

Associations between prenatal exposure to cadmium and lead with neural tube defect risks are modified by single-nucleotide polymorphisms of fetal MTHFR and SOD2: a case-control study.

Environ Health 2021 Jun 5;20(1):66. Epub 2021 Jun 5.

Institute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.

Background: Prenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations.

Methods: This study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model.

Results: Higher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)].

Conclusions: Prenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.
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http://dx.doi.org/10.1186/s12940-021-00752-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180011PMC
June 2021

The association between severe or death COVID-19 and solid organ transplantation: A systematic review and meta-analysis.

Transplant Rev (Orlando) 2021 May 21;35(3):100628. Epub 2021 May 21.

Department of Geriatric Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan, China. Electronic address:

Background: The effect of solid organ transplantation (SOT) on the severity and mortality of coronavirus disease 2019 (COVID-19) remained controversial. There is still no consensus on whether solid organ transplantation (SOT) recipients with COVID-19 are at greater risk of developing severe or fatal COVID-19. Therefore, we conducted a systematic review and meta-analysis to investigate the association between SOT, severe COVID-19 illness, and mortality.

Methods: A systemically comprehensive search in Pubmed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure was performed for relevant studies and articles. Consequently, we pooled the odds ratio (OR) from individual studies and performed heterogeneity, quality assessment and subgroup/sensitivity analysis.

Results: A total number of 15 articles with 265,839 participants were included in this study. Among the total number of participants, 1485 were SOT recipients. The meta-analysis results showed that transplant patients with COVID-19 were remarkably associated with a higher risk of intensive care unit admission than non-transplant patients (OR = 1.57, 95%CI: 1.07 to 2.31, P = 0.02). On the other hand, there were no statistically significant differences between SOT recipients and non-SOT recipients in mechanical ventilation need (OR = 1.55, 95%CI: 0.98 to 2.44, P = 0.06). In addition, we found that SOT recipients with COVID-19 had 1.40-fold increased odds of mortality than non-SOT recipients (OR = 1.40, 95%CI: 1.10 to 1.79, P = 0.007). Moreover, pooled analysis of adjusted results revealed that SOT recipients had a greater risk of mortality compared with non-SOT patients (HR = 1.54, 95%CI: 1.03 to 2.32, P = 0.037).

Limitations: The main limitations in our study are attributed to the relatively small sample size, short follow-up period, and the fact that most of the studies included were retrospective in design.

Conclusions: The results of this study indicate that SOT recipients with COVID-19 had a more significant risk of COVID-19 severity and mortality than the general population.
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http://dx.doi.org/10.1016/j.trre.2021.100628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137345PMC
May 2021

Targeted Sequencing Facilitated Diagnosis of an Uncommon Patient Harboring Both Multiple Primary and Intrapulmonary Metastatic Lung Cancer: A Case Report.

Onco Targets Ther 2021 26;14:3455-3459. Epub 2021 May 26.

Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, 071000, People's Republic of China.

Estimated to comprise approximately 10% of lung cancer cases, multiple pulmonary lesions pose a diagnostic and therapeutic challenge in thoracic oncology. Distinction between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) directly affects tumor staging and clinical management. In equivocal cases in which the lesions are histopathologically indistinguishable, targeted sequencing can provide key additional evidence for differential diagnosis. Herein, we describe an unusual patient who presented with seven lung lesions that consisted of primary tumors and metastatic lesions, each showing distinct clonality status based on histomolecular findings. Specifically, the 45-year-old female never-smoker underwent a surgery that removed one invasive lepidic predominant adenocarcinoma and five microinvasive adenocarcinomas. Next-generation sequencing revealed three of the lesions to carry a clonal driver mutation p.L858R, supporting an IMP diagnosis. p.L858R was not detected in two other surgical specimens, which instead harbored respective oncogenic p.G469A and an uncommon p.G779F. These results led to diagnosis of the two lesions as primary tumors of lineages different from that of the metastases. The patient had achieved a recurrence-free survival of 21 months as of the latest follow-up. In this rare case that presented with evidence of both MPLC and IPM, targeted sequencing proved valuable in facilitating the diagnostic workup.
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http://dx.doi.org/10.2147/OTT.S309155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165299PMC
May 2021

Increased expression of transient receptor potential channels and neurogenic factors associates with cough severity in a guinea pig model.

BMC Pulm Med 2021 Jun 2;21(1):187. Epub 2021 Jun 2.

Department of Respiratory Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23rd Art Museum Backstreet, Dongcheng District, Beijing, 10010, China.

Background: Previous studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, although the details of mechanism are largely unknown. Here, we aimed to further explore the potential mechanism involved in IPF-related high cough sensitivity to capsaicin challenge in a guinea pig model of pulmonary fibrosis induced by bleomycin.

Methods: Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to measure the expression of TRP channel subfamily A, member 1 (TRPA1) and TRP vanilloid 1 (TRPV1), which may be involved in the cough reflex pathway. Immunohistochemical analysis and RT-qPCR were used to detect the expression of neuropeptides substance P (SP), Neurokinin-1 receptor (NK1R), and calcitonin gene-related peptide (CGRP) in lung tissues. Concentrations of nerve growth factor (NGF), SP, neurokinin A (NKA), neurokinin B (NKB), and brain-derived neurotrophic factor (BDNF) in lung tissue homogenates were measured by ELISA.

Results: Cough sensitivity to capsaicin was significantly higher in the model group than that of the sham group. RT-qPCR and immunohistochemical analysis showed that the expression of TRPA1 and TRPV1 in the jugular ganglion and nodal ganglion, and SP, NK1R, and CGRP in lung tissue was significantly higher in the model group than the control group. In addition, expression of TRP and neurogenic factors was positively correlated with cough sensitivity of the experimental animals.

Conclusion: Up-regulated expression of TRPA1 and TRPV1 in the cough reflex pathway and neurogenic inflammation might contribute to the IPF-related high cough sensitivity in guinea pig model.
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http://dx.doi.org/10.1186/s12890-021-01556-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173754PMC
June 2021

A minimally disruptive method for measuring water potential in planta using hydrogel nanoreporters.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;

Leaf water potential is a critical indicator of plant water status, integrating soil moisture status, plant physiology, and environmental conditions. There are few tools for measuring plant water status (water potential) in situ, presenting a critical barrier for developing appropriate phenotyping (measurement) methods for crop development and modeling efforts aimed at understanding water transport in plants. Here, we present the development of an in situ, minimally disruptive hydrogel nanoreporter (AquaDust) for measuring leaf water potential. The gel matrix responds to changes in water potential in its local environment by swelling; the distance between covalently linked dyes changes with the reconfiguration of the polymer, leading to changes in the emission spectrum via Förster Resonance Energy Transfer (FRET). Upon infiltration into leaves, the nanoparticles localize within the apoplastic space in the mesophyll; they do not enter the cytoplasm or the xylem. We characterize the physical basis for AquaDust's response and demonstrate its function in intact maize ( L.) leaves as a reporter of leaf water potential. We use AquaDust to measure gradients of water potential along intact, actively transpiring leaves as a function of water status; the localized nature of the reporters allows us to define a hydraulic model that distinguishes resistances inside and outside the xylem. We also present field measurements with AquaDust through a full diurnal cycle to confirm the robustness of the technique and of our model. We conclude that AquaDust offers potential opportunities for high-throughput field measurements and spatially resolved studies of water relations within plant tissues.
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http://dx.doi.org/10.1073/pnas.2008276118DOI Listing
June 2021

Application of Nano-Drug Delivery System Based on Cascade Technology in Cancer Treatment.

Int J Mol Sci 2021 May 27;22(11). Epub 2021 May 27.

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

In the current cancer treatment, various combination therapies have been widely used, such as photodynamic therapy (PDT) combined with chemokinetic therapy (CDT). However, due to the complexity of the tumor microenvironment (TME) and the limitations of treatment, the efficacy of current treatment options for some cancers is unsatisfactory. Nowadays, cascade technology has been used in cancer treatment and achieved good therapeutic effect. Cascade technology based on nanotechnology can trigger cascade reactions under specific tumor conditions to achieve precise positioning and controlled release, or amplify the efficacy of each drug to improve anticancer efficacy and reduce side effects. Compared with the traditional treatment, the application of cascade technology has achieved the controllability, specificity, and effectiveness of cancer treatment. This paper reviews the application of cascade technology in drug delivery, targeting, and release via nano-drug delivery systems in recent years, and introduces their application in reactive oxygen species (ROS)-induced cancer treatment. Finally, we briefly describe the current challenges and prospects of cascade technology in cancer treatment in the future.
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http://dx.doi.org/10.3390/ijms22115698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199020PMC
May 2021

miR-24 protects against ischemia-induced brain damage in rats via regulating microglia polarization by targeting Clcn3.

Neurosci Lett 2021 May 29;759:135998. Epub 2021 May 29.

Department of Emergency Neurology, Yidu Central Hospital of Weifang, Qingzhou 262500, Shandong Province, China.

Microglia and macrophages play important roles in ischemic brain injury. Changes in their M1/M2 polarization phenotypes significantly impact disease progression. The M2 microglia/macrophages are anti-inflammatory and have a protective effect against ischemic injury. The microRNA 24 (miR-24) promotes M2 macrophage polarization and suppresses inflammation. We tested the hypothesis that miR-24 is protective in ischemic brain injury by regulating microglia polarization. We treated rats with miR-24 inhibitor or mimic and subsequently subjected the rats to middle cerebral artery occlusion (MCAO) to induce ischemic brain injury. Neurological deficit and infarct volume were analyzed. Microglia and macrophages were assessed by fluorescence-activated cell sorting. Microglia polarization was determined by genes specific for M1 and M2 both in vivo and in BV-2 cells. The effect of miR-24 target Clcn3 on microglia polarization was examined. We found that miR-24 inhibition aggravated MCAO induced damage, while miR-24 overexpression alleviated brain injury by suppressing microglia/macrophage infiltration. miR-24 suppressed M1 and promoted M2 microglia polarization both in vivo and in vitro. Finally, we showed that miR-24 targeted Clcn3 to regulate microglia polarization. Our study indicates that miR-24 plays a neuroprotective role by promoting anti-proinflammatory microglia polarization during ischemic brain injury.
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http://dx.doi.org/10.1016/j.neulet.2021.135998DOI Listing
May 2021

Factors affecting the migration of ILC2s in allergic disease.

Cell Mol Immunol 2021 May 31. Epub 2021 May 31.

Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1038/s41423-021-00703-xDOI Listing
May 2021

The targetable nanoparticle [email protected] represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer.

J Nanobiotechnology 2021 May 31;19(1):165. Epub 2021 May 31.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.

Background: Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed.

Results: We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Database showed S1PR1 is highly expressed in BRCA and causes the poor prognosis of patients. Interrupting the expression of S1PR1 could inhibit the growth of human breast cancer cells (MCF-7 and MDA-MB-231) and suppress the angiogenesis of human umbilical vein endothelial cells (HUVECs) via affecting S1PR1/P-STAT3/VEGFA axis. Siponimod (BAF312) is a selective antagonist of S1PR1, which inhibits tumor growth and angiogenesis in vitro by downregulating the S1PR1/P-STAT3/VEGFA axis. We prepared pH-sensitive and tumor-targeted shell-core structure nanoparticles, in which hydrophilic PEG2000 modified with the cyclic Arg-Gly-Asp (cRGD) formed the shell, hydrophobic DSPE formed the core, and CaP (calcium and phosphate ions) was adsorbed onto the shell; the nanoparticles were used to deliver BAF312 ([email protected]). The size and potential of the nanoparticles were 109.9 ± 1.002 nm and - 10.6 ± 0.056 mV. The incorporation efficacy for BAF312 was 81.4%. Results confirmed [email protected] could dramatically inhibit tumor growth and angiogenesis in vitro and in MDA-MB-231 tumor-bearing mice via downregulating the S1PR1/P-STAT3/VEGFA axis.

Conclusions: Our data suggest a potent role for [email protected] in treating BRCA, especially TNBC by downregulating the S1PR1/P-STAT3/VEGFA axis.
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http://dx.doi.org/10.1186/s12951-021-00904-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167992PMC
May 2021

Assessment of Modifiable Factors for the Association of Marital Status With Cancer-Specific Survival.

JAMA Netw Open 2021 May 3;4(5):e2111813. Epub 2021 May 3.

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

Importance: Married patients with cancer have better cancer-specific survival than unmarried patients. Increasing the early diagnosis and definitive treatment of cancer among unmarried patients may reduce the survival gap.

Objectives: To evaluate the extent to which marriage is associated with cancer-specific survival, stage at diagnosis, and treatment among patients with 9 common solid cancers and to recommend methods for reducing the survival gap.

Design, Setting, And Participants: This retrospective, population-based cohort study included patients older than 18 years who were diagnosed with 1 of 9 common cancers between January 1, 2007, and December 31, 2016. Patient data were retrieved from the Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed from August 1 to October 1, 2020.

Exposures: Marital status, classified as married and unmarried (including single, separated, divorced, widowed, and unmarried patients or domestic partners).

Main Outcomes And Measures: The primary outcome was the time ratio (TR) of cancer-specific survival (married vs unmarried). Mediation analyses were conducted to determine the extent to which the association of marriage with cancer-specific survival was mediated by stage at diagnosis and treatment.

Results: This study included 1 733 906 patients (894 379 [51.6%] women; 1 067 726 [61.6%] married; mean [SD] age, 63.76 [12.60] years). Multivariate analyses found that those who were married were associated with better cancer-specific survival than unmarried patients (TR, 1.36; 95% CI, 1.35-1.37). Early diagnosis in breast cancer, colorectal cancer, endometrial cancer, and melanoma mediated the association between marital status and cancer-specific survival (breast cancer: proportion mediated [PM], 11.4%; 95% CI, 11.2%-11.6%; colorectal cancer: PM, 10.9%; 95% CI, 10.7%-11.2%; endometrial cancer: PM, 12.9%; 95% CI, 12.5%-13.3%; melanoma: PM, 12.0%; 95% CI, 11.7-12.4%). Surgery mediated the association between marital status and cancer-specific survival in lung (PM, 52.2%; 95% CI, 51.9%-52.4%), pancreatic (PM, 28.9%; 95% CI, 28.6%-29.3%), and prostate (PM, 39.3%; 95% CI, 39.0%-39.6%) cancers. Chemotherapy mediated the association of marital status with cancer-specific survival in lung (PM, 37.7%; 95% CI, 37.6%-37.9%) and pancreatic (PM, 28.6%; 95% CI, 28.4%-28.9%) cancers. Improved cancer-specific survival associated with marriage was greater among men than women (men: TR, 1.27; 95% CI, 1.25-1.28; women: TR, 1.20; 95% CI, 1.19-1.21). The contribution of receiving an early diagnosis and treatment with surgery or chemotherapy to the association between marital status and cancer-specific survival was greater among men than women (early diagnosis: PM, 21.7% [95% CI, 21.5%-21.9%] vs PM, 20.3% [95% CI, 20.2%-20.4%]; surgery: PM, 26.6% [95% CI, 26.4%-26.7%] vs PM, 11.1% [95% CI, 11.0%-11.2%]; chemotherapy: PM, 6.8% [95% CI, 6.7%-6.8%] vs PM, 5.1% [95% CI, 5.0%-5.2%]).

Conclusions And Relevance: In this study, survival disparities associated with marital status were attributable to early diagnosis in breast, colorectal, and endometrial cancers as well as melanoma and to treatment-related variables in lung, pancreatic, and prostate cancers. The findings also suggest that marriage may play a greater protective role in the cancer-specific survival of men than of women.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.11813DOI Listing
May 2021

Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade.

FASEB J 2021 Jun;35(6):e21555

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Preeclampsia (PE) is a life-threatening disease of pregnant women associated with severe hypertension, proteinuria, or multi-organ injuries. Mitochondrial-mediated placental oxidative stress plays a key role in the pathogenesis of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, regulating placental mitochondrial reactive oxygen species (ROS). We showed that Rnd3 is down-regulated in primary trophoblasts isolated from PE patients. Loss of Rnd3 in trophoblasts resulted in excessive ROS generation, cell apoptosis, mitochondrial injury, and proton leakage from the respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Rnd3 physically interacts with the peroxisome proliferators-activated receptor γ (PPARγ) and promotes the PPARγ-mitochondrial uncoupling protein 2 (UCP2) cascade. Forced expression of PPARγ rescues deficiency of Rnd3-mediated mitochondrial dysfunction. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling and highlight that downregulation of Rnd3 is a potential factor involved in PE pathogenesis.
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http://dx.doi.org/10.1096/fj.202002639RRRDOI Listing
June 2021

LDL‑induced NLRC3 inflammasome activation in cardiac fibroblasts contributes to cardiomyocytic dysfunction.

Mol Med Rep 2021 Jul 26;24(1). Epub 2021 May 26.

Department of Gastroenterology, Feicheng Mining Center Hospital, Feicheng, Shandong 271600, P.R. China.

Heart failure (HF) is a progressive myocardial disease that affects pulse rate. Notably, chronic inflammation serves a crucial role in cardiac dysfunction and HF. Appropriate cardiomyocyte‑fibroblast communication is essential for cardiac function. In addition, cardiac fibroblasts (CFs) are the main cellular population in the cardiac microenvironment; therefore, determining the role of CFs in HF progression and the associated molecular basis is important. In the present study, ELISAs were performed to detect inflammatory factors in the sera of patients with HF and their association with CF activation was analyzed using Pearson's correlation coefficient. The mechanism underlying the proinflammatory phenotype of CFs was investigated via western blotting. Notably, the levels of IL10 and TNF‑α were significantly increased in the sera of patients with HF. Further analysis revealed that CFs were extensively activated in the cardiac tissues of patients with HF and released excessive amounts of cytokines, which could impair the viability of cardiomyocytes. Moreover, low‑density lipoprotein (LDL)‑induced NLRC3 inflammasome was activated in CFs, which gave rise to proinflammatory phenotypes. Targeting LDL in CFs significantly improved the functioning of cardiomyocytes and inhibited apoptosis. These findings highlighted the critical role of LDL in inflammasome activation; to the best of our knowledge, the present study is the first to reveal that CF‑induced microenvironmental inflammation may suppress cardiomyocyte viability. The present study established the cellular basis for CF activation during HF progression and provided information on the cellular interactions important for HF treatment.
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http://dx.doi.org/10.3892/mmr.2021.12165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170230PMC
July 2021

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial.

Cancer Control 2021 Jan-Dec;28:1073274821997444

Department of Chemotherapy, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Objectives: The aim of this study was to assess the clinical usefulness of cetuximab and cisplatin alone or in combination with paclitaxel as the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Methodology: Three hundred patients with confirmed HNSCC from 20 different hospitals were included in this study. Patients in group I underwent a 2-hour infusion of 400 mg/m cetuximab (day 1), followed by a 1-hour infusion of 250 mg/m cetuximab weekly and 1-hour infusion of 100 mg/m cisplatin (days 1 and 21) per treatment cycle. Patients in group II were treated with a combination of cetuximab, cisplatin, and paclitaxel. Patients received 6 cycles of 175 mg/m paclitaxel given on days 1 and 21. The primary outcome of the study was progression-free survival (PFS); overall survival (OS) and objective response rate (ORR) were the secondary endpoints.

Results: The median PFS was 5 months and 8 months for patients in groups I and II, respectively (HR, 0.93; 95% CI, 0.85-1.78; > 0.05). Similarly, we found no significant differences in OS between the 2 groups (median OS, 13 vs. 11 months, respectively; HR, 0.67; 95% CI, 0.42-1.43; = 0.198). Moreover, we observed no significant difference in ORR between the 2 groups (ORR, 63.3% vs 69.9%, respectively; HR, 0.87; 95% CI, 0.36-1.67; = 0.231).

Conclusions: The combination of paclitaxel with cetuximab and cisplatin did not improve patient outcomes compared to cetuximab plus cisplatin alone. Therefore, the 2-drug regimen could be used as first-line treatment in patients with recurrent or metastatic HNSCC.
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http://dx.doi.org/10.1177/1073274821997444DOI Listing
May 2021

Evaluation of Oncology Trial Results Reporting Over a 10-Year Period.

JAMA Netw Open 2021 May 3;4(5):e2110438. Epub 2021 May 3.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, China.

Importance: Unreported clinical trial results represent a violation of human rights. Oncology trials account for nearly 30% of interventional biopharmaceutical clinical studies registered on ClinicalTrials.gov and are the most numerous among all disciplines.

Objective: To analyze the reporting of results among all interventional oncology trials registered on ClinicalTrials.gov from 2007 through 2017.

Design, Setting, And Participants: This cohort study analyzed all clinical studies registered between June 1, 2007, and May 8, 2017, on ClinicalTrials.gov, the largest public clinical trial registry in the world. Trials with a recruitment status of completed or terminated and a primary completion date of on or before September 30, 2017, were selected. Data were analyzed between February 20, 2021, and February 26, 2021.

Main Outcomes And Measures: The main outcome was the percentage of trials that reported results either on ClinicalTrials.gov or in journal publications within 24 months of the primary completion date. Journal publication was ascertained by searching ClinicalTrials.gov for a link to the publication, PubMed using national clinical trial number, and Embase using national clinical trial number and filters.

Results: Of the 12 240 clinical trials registered in ClinicalTrials.gov, 7425 trials (60.7%; 95% CI, 60.0%-61.5%) reported results, with a 34.0% (95% CI, 30.3%-37.7%) increase in 24-month reporting rate from 2007 to 2017. Multivariable analyses confirmed that more recent trials (adjusted hazard ratio [HR], 1.11 per year increase; 95% CI, 1.10-1.13) and trials with larger sample sizes (51-100 patients: adjusted HR, 1.17 [95% CI, 1.09-1.24]; >100 patients: adjusted HR, 1.43 [95% CI, 1.33-1.54]) were more likely to report results. Terminated trials were less likely to report results compared with completed trials (adjusted HR, 0.88; 95% CI, 0.83-0.93). Compared with trials funded by industry, those funded by the National Institutes of Health were more likely to report results (adjusted HR, 1.39; 95% CI, 1.29-1.49), whereas those funded by other academic or nonprofit organizations were less likely to report results (adjusted HR, 0.66; 95% CI, 0.62-0.70). Among all 7425 trials, the results of 2807 trials (37.8%; 95% CI, 36.7%-38.9%) were posted only on ClinicalTrials.gov. These trials tended to be terminated early and to have small sample sizes (≤50 patients) compared with trials that published results in journals.

Conclusions And Relevance: This study found a gradual improvement in results reporting among oncology trials over a 10-year period. Trial registries could serve as a results reporting platform for unpublished trials and as a data source of trial outcomes for future studies.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.10438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144925PMC
May 2021

Global Observations and CMIP6 Simulations of Compound Extremes of Monthly Temperature and Precipitation.

Geohealth 2021 May 1;5(5):e2021GH000390. Epub 2021 May 1.

State Key Laboratory of Earth Surface Processes and Resource Ecology Faculty of Geographical Science Beijing Normal University Beijing China.

Compound climate extremes, such as events with concurrent temperature and precipitation extremes, have significant impacts on the health of humans and ecosystems. This paper aims to analyze temporal and spatial characteristics of compound extremes of monthly temperature and precipitation, evaluate the performance of the sixth phase of the Coupled Model Intercomparison Project (CMIP6) models in simulating compound extremes, and investigate their future changes under Shared Socioeconomic Pathways (SSPs). The results show a significant increase in the frequency of compound warm extremes (warm/dry and warm/wet) but a decrease in compound cold extremes (cold/dry and cold/wet) during 1985-2014 relative to 1955-1984. The observed upward trends of compound warm extremes over China are much higher than those worldwide during the period of interest. A multi-model ensemble (MME) of CMIP6 models performs well in simulating temporal changes of warm/wet extremes, and temporal correlation coefficients between MME and observations are above 0.86. Under future scenarios, CMIP6 simulations show substantial rises in compound warm extremes and declines in compound cold extremes. Globally, the average frequency of warm/wet extremes over a 30-yr period is projected to increase for 2070-2099 relative to 1985-2014 by 18.53, 34.15, 48.79, and 59.60 under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5, respectively. Inter-model uncertainties for the frequencies of compound warm extremes are considerably higher than those of compound cold extremes. The projected uncertainties in the global occurrences of warm/wet extremes are 3.82 times those of warm/dry extremes during 2070-2099 and especially high for the Amazon and the Tibetan Plateau.
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http://dx.doi.org/10.1029/2021GH000390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121137PMC
May 2021

Spatio-temporal analysis of urban air pollutants throughout China during 2014-2019.

Air Qual Atmos Health 2021 May 14:1-14. Epub 2021 May 14.

Department of Environmental Health, School of Public Health, Key Laboratory of Environmental Health Damage Research and Assessment, China Medical University, Shenyang, 110122 Liaoning Province China.

Air pollution control has become the top priority of China's "green development" concept since 2013. The Chinese government has enacted a range of policies and statutes to control contaminant emissions and improve air quality. On the basis of the national air quality ground observation database, the spatial and temporal distribution of air quality index value (AQI), fine particulate matter (PM), coarse particles (PM), sulfur dioxide (SO), nitrogen dioxide (NO), carbon monoxide (CO), and ozone (O) were explored in 336 cities throughout China from 2014 to 2019. AQI and most pollutants (except O) decreased in concentrations from 2014 to 2019. In 2019, all cities except Henan reached the level 2 of the ambient air quality index, and six cities had a lower ambient air quality index and reached the level 1. Spatially, higher pollutant concentrations were concentrated in large city clusters, whereas the areas with high O concentration were found across the country. Furthermore, central heating was shown to have a negative impact on air quality. The observed AQI value, PM, PM, SO, NO, and CO concentrations were highest in north and northwest China and Henan province in central China. The correlations among pollutants suggest that the main sources of pollutants are fossil fuel combustion, industrial production, and motor vehicle emissions. The influence of meteorological factors on air quality, long-distance transportation, and the transformations of pollutants should be explored in future research.

Supplementary Information: The online version contains supplementary material available at 10.1007/s11869-021-01043-5.
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http://dx.doi.org/10.1007/s11869-021-01043-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121134PMC
May 2021

Pretreatment by composting increased the utilization proportion of pig manure biogas digestate and improved the seedling substrate quality.

Waste Manag 2021 Jun 21;129:47-53. Epub 2021 May 21.

College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China.

Anaerobic digestion of organic residues has the potential to significantly contribute to a shift from fossil to renewable energy, while the remaining biogas digestate need to be treated or used for a second time. In this study, the pig manure biogas digestate (PMBD) was evaluated as a potential part of seedling substrates and composting was considered a pretreating method to improve its characters. Composting was carried out firstly in a forced aeration composting system (100 L), in which perlite and sawdust were used as additives in different proportions separately or together. Based on the comparison of the physicochemical characters of different seedling substrates formulas mixed with PMBD or pig manure biogas digestate pretreated by composting (CPMBD), selected seedling substrates were analyzed by bioassay experiment. The results showed that pretreatment by composting and the additives (perlite and sawdust) used in composting decreased the pH value of PMBD and make it suitable for seedling substrates, especially composted with perlite and sawdust. Both PMBD and CPMBD with low proportion in the substrates improved plant growth of lettuce and tomato, while CPMBD was better than PMBD. However, when the proportions of PMBD was increased more than 20% and CPMBD was increased more than 40%, plant growth inhibition was observed. Tomato was more sensitive than lettuce to the physicochemical characters of the substrate. In summary, PMBD pretreated by composting not only increases the uses of digestate, but also enhances plant growth and hence yield.
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http://dx.doi.org/10.1016/j.wasman.2021.05.010DOI Listing
June 2021

Risk assessment model for heart failure in Chinese patients with Takayasu's arteritis.

Clin Rheumatol 2021 May 22. Epub 2021 May 22.

Department of Rheumatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.

Objectives: We aimed to construct and validate a risk assessment model to identify risk factors for heart failure (HF) in patients with Takayasu's arteritis (TAK).

Methods: Three hundred sixty-five patients with TAK were recruited in the East China Takayasu Arteritis Cohort from January 2012 to December 2019. Patients were assigned into training and validation sets following a 2:1 ratio according to the date of enrollment. Clinical characteristics were compared between heart failure (HF) and non-HF subgroups in the training set, and a risk assessment model for HF and its scoring algorithm was established based on logistic regression, which was tested in the validation set.

Results: Among total of 74 (20.27%) TAK patients exhibited HF, and 55 cases (74.32%) were in the training set. The risk factors for HF of TAK patients included onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension. We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients in the training set with the score ≥ 3 appeared to be associated with an increased risk of HF with an area under curve (AUC) of 0.88 and 0.90 in Model 1 and Model 2 respectively. The AUC reached to 0.88 and 0.89 in the validation set that proved the accuracy of the model.

Conclusions: We presented a risk assessment model of HF in TAK, which may help clinicians alert the complication of HF in the patients with specifically cardiac impairments. Key Points • Heart failure was not rare in Chinese Takayasu's arteritis patients, and there were approximately 20% of patients with heart failure in ECTA cohort. • Cardiac involvements on echocardiography include pathological valvular and atrioventricular abnormalities. • The onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension were risk factors for heart failure in Takayasu's arteritis patients. • We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients with the risk assessment model score of ≥ 3 appeared to be associated with an increased risk of heart failure.
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http://dx.doi.org/10.1007/s10067-021-05745-0DOI Listing
May 2021

TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation.

Cell Death Dis 2021 May 20;12(6):517. Epub 2021 May 20.

Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, China.

Metabolic reprogramming is a hallmark of malignancy. Testes-specific protease 50 (TSP50), a newly identified oncogene, has been shown to play an important role in tumorigenesis. However, its role in tumor cell metabolism remains unclear. To investigate this issue, LC-MS/MS was employed to identify TSP50-binding proteins and pyruvate kinase M2 isoform (PKM2), a known key enzyme of aerobic glycolysis, was identified as a novel binding partner of TSP50. Further studies suggested that TSP50 promoted aerobic glycolysis in HCC cells by maintaining low pyruvate kinase activity of the PKM2. Mechanistically, TSP50 promoted the Warburg effect by increasing PKM2 K433 acetylation level and PKM2 acetylation site (K433R) mutation remarkably abrogated the TSP50-induced aerobic glycolysis, cell proliferation in vitro and tumor formation in vivo. Our findings indicate that TSP50-mediated low PKM2 pyruvate kinase activity is an important determinant for Warburg effect in HCC cells and provide a mechanistic link between TSP50 and tumor metabolism.
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http://dx.doi.org/10.1038/s41419-021-03782-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138007PMC
May 2021

Curcumin alleviates inflammation in Takayasu's arteritis by blocking CCL2 overexpression in adventitial fibroblasts.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):161-170. Epub 2021 May 19.

Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, and Evidence-Based Medicine Centre, Fudan University, Shanghai, China.

Objectives: Takayasu's arteritis (TAK) is a chronic inflammatory disease with several challenges in treatment. Curcumin is known for its anti-inflammatory effects, whereas its effect in the treatment of TAK remains unclear. In this study, we aimed to investigate the effect of curcumin in the treatment of TAK and its underlying mechanisms.

Methods: 16 TAK patients were treated with curcumin granules at a dose of 15 g/day for three months. Kerr score was explored to assess disease activity. Serum levels of inflammatory factors were measured by ELISA. Immunohistochemical and immunofluorescence staining were used to detect the expression of CCL2 (also known as MCP-1) in aortic adventitia. RT-qPCR, ELISA and western blot were used to determine the regulatory effect of curcumin on CCL2 expression in aortic adventitia fibroblasts (AAFs) and its mechanism.

Results: Curcumin treatment significantly lowered Kerr score and the levels of serum CCL2 in TAK patients. The expression of CCL2 in TAK aortic adventitia was increased and colocalised with CD68. Serum levels of CCL2 was increased in subjects with Kerr score ≥2. After curcumin treatment, the changes in CCL2 were positively associated with the changes in IL-6. In further analysis, it showed that CCL2 was co-localised with CD90 and α-SMA, markers of adventitia fibroblasts. In vitro, HSP65, an agonist of TLR4, could induce CCL2 expression in AAFs via phosphorylating and activating the JAK2/AKT/STAT3 pathway. Nevertheless, curcumin could reverse the HSP65-induced CCL2 upregulation through restraining JAK2/AKT/STAT3 pathway. The inhibitory effect of curcumin on the JAK2/AKT/STAT3 pathway was even more obvious than that of methotrexate and tofacitinib.

Conclusions: Curcumin alleviated inflammation in TAK by downregulating CCL2 overexpression in AAFs through inhibiting the JAK2/AKT/STAT3 signalling pathway.
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May 2021

A kelch-repeat superfamily gene, ZmNL4, controls leaf width in maize (Zea mays L.).

Plant J 2021 May 19. Epub 2021 May 19.

State Key Laboratory for Agrobiotechnology and Key Laboratory of Crop Heterosis and Utilization (MOE) and Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing, 100193, PR China.

Leaf width (LW) is an important component of plant architecture that extensively affects light capture during photosynthesis and grain yield particularly under dense planting conditions. However, the genetic and molecular mechanisms regulating LW remain largely elusive in maize (Zea mays L.). In this study, qLW4a, one major quantitative trait locus controlling LW, was identified in the population constructed by maize inbred lines PH6WC with wide leaf and Lin387 with narrow leaf. Map-based cloning revealed that ZmNL4, a kelch-repeat superfamily gene, emerged to be the candidate for qLW4a, and a single-base deletion in the conserved SMC_prok_B domain of ZmNL4 in Lin387 caused a frame shift leading to a prematurely termination. Consistently, knockout of ZmNL4 by CRISPR/Cas9 editing significantly reduced LW, which was attributed to a reduction in the cell number instead of cell size, indicating a role of ZmNL4 in regulating cell division. Transcriptomic comparison between ZmNL4 knockout lines and the wild type B73-329 revealed that ZmNL4 might participate in cell wall biogenesis, asymmetric cell division, metabolic process, transmembrane transport and response to external stimulus, etc. These results provided insights into the genetic and molecular mechanisms of ZmNL4 in controlling LW and potentially contributed to optimize plant architecture for maize breeding.
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http://dx.doi.org/10.1111/tpj.15348DOI Listing
May 2021

Changes in NSE and S-100β during the perioperative period and effects on brain injury in infants with biliary atresia undergoing parent donor liver transplantation.

Exp Ther Med 2021 Jul 4;22(1):724. Epub 2021 May 4.

Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, P.R. China.

The present study aimed to investigate the effects of parental donor liver transplantation on the perioperative changes of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) levels, two markers of brain injury, and on postoperative cognitive function. The present study was a prospective observational study of infants with congenital biliary atresia who underwent selective liver transplantation in 2017 at Tianjin First Central Hospital (Tianjin, China). Blood samples were collected prior to, during and following surgery, and S-100β and NSE levels were measured using ELISA. The pediatric patients were assessed using the Bayley Scales of Infant Development 1 day prior to and 3 months after surgery. Additionally, the pediatric anesthesia emergence delirium scores were evaluated. The results demonstrated that serum NSE and S100β were increased during and after surgery compared with prior to surgery (P<0.05). Furthermore, serum S-100β and NSE levels peaked 1 h after the neohepatic phase compared with prior to surgery (P<0.05). Compared with 1 day before surgery, mental development index (MDI) and psychomotor development index (PDI) were decreased 3 months after surgery (MDI, 87.7±8.4 vs. 84.5±8.5, P=0.015; PDI, 82.9±8.7 vs. 79.6±8.8, P=0.016). In conclusion, parental donor liver transplantation may cause a certain degree of brain injury in pediatric patients with end-stage liver disease, as revealed by increased serum NSE and S100β levels.
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http://dx.doi.org/10.3892/etm.2021.10156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120510PMC
July 2021

Association of oral microbiota profile with sugar-sweetened beverages consumption in school-aged children.

Int J Food Sci Nutr 2021 May 17:1-11. Epub 2021 May 17.

Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, China.

Evidence that common beverage consumption is associated with oral ecosystem. However, little is known about the effect of sugar-sweetened beverages (SSBs) on composition and functional potential of childhood oral microbiota. We aim to examine associations between SSBs consumption with oral microbiota diversity and function among school-aged children. Oral microbiota in buccal swab samples was collected from 180 children (11.3 ± 0.6 years) from an ongoing child growth and development cohort established in 2016, using 16S rDNA gene sequencing. Higher SSBs consumption (≥1 serving/day) was associated with lower oral microbiota richness and diversity. Children with higher SSBs consumption showed decreased abundance of genus and ( < 0.05). However, more SSBs intake selectively increases the dominance of aciduric bacteria ( and , which can lead to dental caries and other oral problems. Furthermore, PICRUSt analysis illustrated that oral microbiota was more conducive to the pathway activated of protein export ( = 0.020), D-glutamine and D-glutamate metabolism ( = 0.013), and pantothenate and CoA biosynthesis ( = 0.004), indicating vigorous microbial metabolism in oral bacterial community in higher SSBs intake groups. Overall, our finding suggests that higher SSBs consumption may disturb oral microecology and reduce diversity of microbiota during childhood, stimulating an increase in cariogenic genera, which contributes to increased susceptibility of SSBs-related oral diseases.
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http://dx.doi.org/10.1080/09637486.2021.1913102DOI Listing
May 2021