Publications by authors named "Yao Chen"

1,573 Publications

  • Page 1 of 1

BATF regulates progenitor to cytolytic effector CD8 T cell transition during chronic viral infection.

Nat Immunol 2021 Jul 19. Epub 2021 Jul 19.

Blood Research Institute, Versiti, Milwaukee, WI, USA.

During chronic viral infection, CD8 T cells develop into three major phenotypically and functionally distinct subsets: Ly108TCF-1 progenitors, Ly108CXCR1 terminally exhausted cells and the recently identified CXCR1 cytotoxic effector cells. Nevertheless, how CXCR1 effector cell differentiation is transcriptionally and epigenetically regulated remains elusive. Here, we identify distinct gene regulatory networks and epigenetic landscapes underpinning the formation of these subsets. Notably, our data demonstrate that CXCR1 effector cells bear a striking similarity to short-lived effector cells during acute infection. Genetic deletion of Tbx21 significantly diminished formation of the CXCR1 subset. Importantly, we further identify a previously unappreciated role for the transcription factor BATF in maintaining a permissive chromatin structure that allows the transition from TCF-1 progenitors to CXCR1 effector cells. BATF directly bound to regulatory regions near Tbx21 and Klf2, modulating their enhancer accessibility to facilitate the transition. These mechanistic insights can potentially be harnessed to overcome T cell exhaustion during chronic infection and cancer.
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http://dx.doi.org/10.1038/s41590-021-00965-7DOI Listing
July 2021

Quantification of ATP in cell by fluorescence spectroscopy based on generalized ratio quantitative analysis model.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 10;263:120170. Epub 2021 Jul 10.

Hunan Key Lab of Biomedical Materials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412008, PR China. Electronic address:

In this contribution, fluorescence spectroscopy based on G-quadruplex formation was developed for the quantification of ATP in cell. In the absence of ATP, thioflavin T (ThT) dye can combine with the G-rich ATP aptamer to form an ATP aptamer-ThT G-quandruplex complex, resulting in the enhancement of fluorescence intensity; otherwise, fluorescence intensity of the system will weaken with the addition of ATP, because ATP has a strong affinity with G-rich ATP aptamer and can replace ThT to form an ATP aptamer-ATP complex. A calibration model based on generalized ratio quantitative analysis model was employed to mitigate the influence of scatterers and background absorbers in cell suspensions. The proposed fluorescence method was applied to the quantitative analysis of ATP in two type of cell lines, and achieved satisfactory quantitative results with accuracy comparable to that of the reference method-ATP detection kit. The limit of detection and limit of quantification of the proposed method for ATP in cell were estimated to be 0.22 and 0.66 μM, respectively. This proposed fluorescence method is highly simple and rapid, and does not require the use of fluorescent labeling.
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http://dx.doi.org/10.1016/j.saa.2021.120170DOI Listing
July 2021

Construction of rGO-Encapsulated Co O -CoFe O Composites with a Double-Buffer Structure for High-Performance Lithium Storage.

Small 2021 Jul 15:e2101080. Epub 2021 Jul 15.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, P. R. China.

Transition metal oxides (TMOs) are promising anode materials for next-generation lithium-ion batteries (LIBs). Nevertheless, their poor electronic and ionic conductivity as well as huge volume change leads to low capacity release and rapid capacity decay. Herein, a reduced graphene oxide (rGO)-encapsulated TMOs strategy is developed to address the above problems. The Co O -CoFe O @rGO composites with rGO sheets-encapsulated Co O -CoFe O microcubes are successfully constructed through a simple metal-organic frameworks precursor route, in which Co[Fe(CN) NO] microcubes are in situ coated by graphene oxide sheets, followed by a two-step calcination process. As anode material of LIBs, Co O -CoFe O @rGO exhibits remarkable reversible capacity (1393 mAh g at 0.2 A g after 300 cycles), outstanding long-term cycling stability (701 mAh g at 2.0 A g after 500 cycles), and excellent rate capability (420 mAh g at 4.0 A g ). The superior lithium storage performance can be attributed to the unique double-buffer structure, in which the outer flexible rGO shells can prevent the structure collapse of the electrode and improve its conductivity, while the hierarchical porous cores of Co O -CoFe O microcubes can buffer the volume expansion. This work provides a general and straightforward strategy for the construction of novel rGO-encapsulated bimetal oxides for energy storage and conversion application.
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http://dx.doi.org/10.1002/smll.202101080DOI Listing
July 2021

Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism.

J Diabetes Res 2021 23;2021:6707464. Epub 2021 Jun 23.

Thyroid Research Center of Shanghai, Shanghai 200072, China.

Characteristic bone metabolism was observed in obesity and diabetes with controversial conclusions. Type 2 diabetes (T2DM) and obesity may manifest increased bone mineral density. Also, obesity is more easily to occur in T2DM. Therefore, we infer that some factors may be linked to bone and obesity as well as glucose metabolism, which regulate all of them. Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor- (TGF-) beta superfamily, regulate a diverse array of cellular functions during development and in the adult. More and more studies revealed that there exists a relationship between bone metabolism and obesity as well as glucose metabolism. BMP2, BMP4, BMP6, BMP7, and BMP9 have been shown to affect the pathophysiological process of obesity and glucose metabolism beyond bone metabolism. They may exert functions in adipogenesis and differentiation as well as insulin resistance. In the review, we summarize the literature on these BMPs and their association with metabolic diseases including obesity and diabetes.
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http://dx.doi.org/10.1155/2021/6707464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249130PMC
June 2021

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

Lancet Oncol 2021 Jul 9. Epub 2021 Jul 9.

Department of General Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China.

Background: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy.

Methods: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m on day one of each 21 day cycle plus oral capecitabine 1000 mg/m twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546.

Findings: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported.

Interpretation: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer.

Funding: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00297-7DOI Listing
July 2021

Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study.

Open Med (Wars) 2021 23;16(1):322-331. Epub 2021 Feb 23.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China.

Objectives: This multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI.

Method: A total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group.

Results: There was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123-2.219; = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212-1.939; 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222-0.729; = 0.003) was independent protective factors for post-OLT AKI.

Conclusion: This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored.
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http://dx.doi.org/10.1515/med-2020-0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256391PMC
February 2021

The neurotrophic and antineuroinflammatory effects of phenylpropanoids from Zanthoxylum nitidum var. tomentosum (Rutaceae).

Fitoterapia 2021 Jul 9;153:104990. Epub 2021 Jul 9.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, People's Republic of China. Electronic address:

Three novel lignans (1, 5 and 6) and two novel quinic acids (16 and 17) along with 15 known phenylpropanoids were obtained from the ethanol extract of Zanthoxylum nitidum var. tomentosum (Rutaceae). Their structures were confirmed by comprehensive spectroscopic data (NMR and HRESIMS), and the absolute configurations of all novel compounds were elucidated based on electronic circular dichroism (ECD) spectroscopic data. The production of nitric oxide (NO) in BV-2 microglial cells induced through lipopolysaccharide (LPS) was used to evaluate in vitro anti-neuroinflammatory activity of compounds 1-20. Compound 2, 3, 7 and 16 showed excellent inhibition of LPS-induced NO production. The structure-activity relationships of the isolates were investigated. In addition, the mechanism of action of 2 was elucidated by RT-PCR and Western blotting analysis, which indicated that it reduced neuroinflammatory mainly through NLRP3/caspase1 signaling pathways in LPS-induced BV2 microglial cells.
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http://dx.doi.org/10.1016/j.fitote.2021.104990DOI Listing
July 2021

The effects of Fe(III) and Fe(II) on anammox process and the Fe-N metabolism.

Chemosphere 2021 Jun 25;285:131322. Epub 2021 Jun 25.

Beijing Key Laboratory of Aqueous Typical Pollutants Control and Water Quality Safeguard, Department of Municipal and Environmental Engineering, School of Civil Engineering, Beijing Jiaotong University, Beijing, 100044, PR China.

This study aims to compare the effects of different Fe stress on anammox (anaerobic ammonium oxidation) process, therefore seven identical reactors were operated under different Fe(II)/Fe(III) concentrations. After 38 days of operation, the anammox activity was highest (10.49 ± 0.41 mg-TN/(g-VSS·h)) under conditions of 5 mg/L-Fe(II), while under 30 mg/L-Fe(III) displayed severe inhibition. The results showed that continuous addition of 30 mg/L-Fe(III) would damage the composition of EPS (extracellular polymeric substances) and make anammox bacteria more sensitive to environmental stress. While high Fe(II) concentrations could result in precipitates encasing granular sludge, affecting substrate utilization. Moreover, the results of ΔNO-N/ΔNH-N indicated that Fe(II)-dependent nitrate reduction was induced in reactors added with Fe(II). OM27_clade and norank_f__Burkholderiaceae might be candidates for this process according to the correlation of genera and functional genes (based on the PICRUSt 2 functional prediction). Overall, this research is expected to provide new ideas to the effects of Fe(II)/Fe(III) on anammox and to the practical application of coupled system based on anammox in wastewater treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131322DOI Listing
June 2021

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke.

Front Med 2021 Jul 9. Epub 2021 Jul 9.

Department of Nuclear Medicine and Medical PET Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
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http://dx.doi.org/10.1007/s11684-021-0842-9DOI Listing
July 2021

An Integrative Genomic Strategy Identifies sRAGE as a Causal and Protective Biomarker of Lung Function.

Chest 2021 Jul 5. Epub 2021 Jul 5.

The Framingham Heart Study, Framingham, MA, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background: There are few clinically useful circulating biomarkers of lung function and lung disease. We hypothesized that genome-wide association studies (GWAS) of circulating proteins in conjunction with GWAS of pulmonary traits represents a clinically-relevant approach to identifying causal proteins and therapeutically-useful insights into mechanisms related to lung function and disease.

Study Question: Can an integrative genomic strategy using GWAS of plasma soluble receptor for advanced glycation end-products (sRAGE) levels in conjunction with GWAS of lung function traits identify putatively causal relations of sRAGE to lung function?

Study Design And Methods: Plasma sRAGE levels were measured in 6,861 Framingham Heart Study participants and GWAS of sRAGE was conducted to identify protein quantitative trait loci (pQTL), including cis-pQTL variants at the sRAGE protein-coding gene locus (AGER). We integrated sRAGE pQTL variants with variants from GWAS of lung traits. Colocalization of sRAGE pQTL variants with lung trait GWAS variants was conducted and Mendelian randomization was performed using sRAGE cis-pQTL variants to infer causality of sRAGE for pulmonary traits. Cross-sectional and longitudinal protein-trait association analyses were conducted for sRAGE in relation to lung traits.

Results: Colocalization identified shared genetic signals for sRAGE with lung traits. Mendelian randomization analyses suggested protective causal relations of sRAGE to several pulmonary traits. Protein-trait association analyses demonstrated higher sRAGE levels to be cross-sectionally and longitudinally associated with preserved lung function.

Interpretation: sRAGE is produced by type I alveolar cells and it acts as a decoy receptor to block the inflammatory cascade. Our integrative genomics approach provides evidence for sRAGE as a causal and protective biomarker of lung function and the pattern of associations is suggestive of a protective role of sRAGE against restrictive lung physiology. We speculate that targeting the AGER/sRAGE axis may be therapeutically beneficial for the treatment and prevention of inflammation-related lung disease.
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http://dx.doi.org/10.1016/j.chest.2021.06.053DOI Listing
July 2021

C-type natriuretic peptide stimulates function of the murine Sertoli cells via activation of the NPR-B/cGMP/PKG signaling pathway.

Acta Biochim Pol 2021 Jul 8. Epub 2021 Jul 8.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

C-type natriuretic peptide (CNP) is an important regulator of the male reproductive process. Our previous investigations showed that CNP can significantly stimulate the mRNA expression of androgen-binding protein (Abp) and transferrin (Trf) in the rat Sertoli cells, but the pathways responsible for this process remain to be elucidated. We predict that CNP binds the natriuretic peptide receptor B (NPR-B) to regulate expression of ABP and TRF through the intracellular cyclic guanosine monophosphate (cGMP) pathway. To address this question, in this study, we first confirmed the expression and localization of CNP and NPR-B in rat testes by immunohistochemistry and western blotting. Then, ELISA and real-time PCR were performed to investigate the signaling pathway of CNP in Sertoli cells in rat testes. Our results showed that CNP was mainly localized in the germ cells and Leydig cells, and its receptor, NPR-B, was mostly expressed in the Sertoli cells and vascular endothelial cells. CNP supplementation in the Sertoli cell medium was accompanied by an increase in the amount of intracellular cGMP and in the production of Abp and Trf mRNA, whereas inhibition of PKG with KT5823 led to a decrease in the expression of Abp and Trf mRNA. Moreover, Abp and Trf mRNA were no longer elevated when we used liposome-mediated RNA interference technology to silence the NPR-B gene in a mouse Sertoli cell line (TM4). These results suggest that CNP contributes to the regulation of ABP and TRF in the Sertoli cells through the NPR-B/cGMP/PKG signaling pathways.
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http://dx.doi.org/10.18388/abp.2020_5442DOI Listing
July 2021

Microglia-derived IL-1β promoted neuronal apoptosis through ER stress-mediated signaling pathway PERK/eIF2α/ATF4/CHOP upon arsenic exposure.

J Hazard Mater 2021 Sep 5;417:125997. Epub 2021 May 5.

Department of Occupational and Environmental Health, Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address:

Arsenic is the leading toxicant of hazardous environmental chemicals, which is linked with neurotoxicity including cognitive dysfunction, neurodevelopmental alterations and neurodegenerative disorders. It has been suggested that sustained pro-inflammatory response is one of the triggering factors of arsenic-induced neurotoxicity. Microglia, the immune cells in the central nervous system, response to physiological and pathological stress, and release a large array of pro-inflammatory cytokines if activated excessively. Several studies indicated that arsenic was capable of inducing microglia activation, however, the role of the subsequently released pro-inflammatory cytokines in arsenic-induced neurotoxicity remains to be elucidated. Our findings demonstrated that arsenic-induced cognitive dysfunction, microglia activation, up-regulation and release of IL-1β and ER stress-mediated apoptosis could be attenuated by minocycline, a recognized inhibitor of microglia activation. In addition, the IL-1 receptor antagonist IL-1ra diminished arsenic-induced activation of ER stress-mediated apoptotic pathway PERK/eIF2α/ATF4/CHOP and neuronal apoptosis. Our findings provided evidences that arsenic-induced microglia activation also contributed to neuronal apoptosis through pro-inflammatory cytokine. Microglia-derived IL-1β promoted hippocampal neuronal apoptosis through ER stress-mediated PERK/eIF2α/ATF4/CHOP apoptotic pathway. Neuronal apoptosis induced by prolonged activation of microglia was partially involved in the arsenic-induced cognitive dysfunction.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125997DOI Listing
September 2021

A scoring system for predicting the prognosis of late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation.

Transplant Cell Ther 2021 Jul 3. Epub 2021 Jul 3.

Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address:

Background: Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developed during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with LOSP have high mortality, so it is important to identify prognostic factors.

Objectives: In this study, we aimed to develop a risk score system with broad applicability that could help predict the risk of LOSP-associated mortality.

Study Design: We retrospectively analyzed 100 patients with LOSP after allo-HSCT from June 2009 to July 2017. The assessment variables included immune, nutritional and metabolic parameters at the onset of LOSP.

Results: Of all 100 patients who suffered LOSP after allo-HSCT, 45 (45%) patients eventually died, and 55 (55%) patients were positive for organisms, with the most common being viruses. In the multivariate analysis, higher monocyte (≥0.20 vs. <0.20 × 10/L, P=0.001), higher albumin (≥30.5 vs. <30.5 g/L, P=0.044), lower lactic dehydrogenase (<250 vs. ≥250 U/L, P=0.008) and lower blood urea nitrogen (<7.2 vs. ≥7.2 mmol/L, P=0.026) levels at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the above results showed that the probability of 60-day survival decreased with increasing risk factors and were 96.3% (low-risk group), 49.1% (intermediate-risk group) and 12.5% (high-risk group).

Conclusions: The results indicated that the scoring system used 4 variables could stratify patients with different probabilities of survival after LOSP, which suggested patients' immune, nutritional and metabolic status were crucial for outcome.
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http://dx.doi.org/10.1016/j.jtct.2021.06.031DOI Listing
July 2021

Cardiovascular Biomarkers of Obesity and Overlap With Cardiometabolic Dysfunction.

J Am Heart Assoc 2021 Jul 3;10(14):e020215. Epub 2021 Jul 3.

Cardiology Division Department of Medicine Massachusetts General Hospital Boston MA.

Background Obesity may be associated with a range of cardiometabolic manifestations. We hypothesized that proteomic profiling may provide insights into the biological pathways that contribute to various obesity-associated cardiometabolic traits. We sought to identify proteomic signatures of obesity and examine overlap with related cardiometabolic traits, including abdominal adiposity, insulin resistance, and adipose depots. Methods and Results We measured 71 circulating cardiovascular disease protein biomarkers in 6981 participants (54% women; mean age, 49 years). We examined the associations of obesity, computed tomography measures of adiposity, cardiometabolic traits, and incident metabolic syndrome with biomarkers using multivariable regression models. Of the 71 biomarkers examined, 45 were significantly associated with obesity, of which 32 were positively associated and 13 were negatively associated with obesity (false discovery rate <0.05 for all). There was significant overlap of biomarker profiles of obesity and cardiometabolic traits, but 23 biomarkers, including melanoma cell adhesion molecule (MCAM), growth differentiation factor-15 (GDF15), and lipoprotein(a) (LPA) were unique to metabolic traits only. Using hierarchical clustering, we found that the protein biomarkers clustered along 3 main trait axes: adipose, metabolic, and lipid traits. In longitudinal analyses, 6 biomarkers were significantly associated with incident metabolic syndrome: apolipoprotein B (apoB), insulin-like growth factor-binding protein 2 (IGFBP2), plasma kallikrein (KLKB1), complement C2 (C2), fibrinogen (FBN), and N-terminal pro-B-type natriuretic peptide (NT-proBNP); false discovery rate <0.05 for all. Conclusions We found that the proteomic architecture of obesity overlaps considerably with associated cardiometabolic traits, implying shared pathways. Despite overlap, hierarchical clustering of proteomic profiles identified 3 distinct clusters of cardiometabolic traits: adipose, metabolic, and lipid. Further exploration of these novel protein targets and associated pathways may provide insight into the mechanisms responsible for the progression from obesity to cardiometabolic disease.
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http://dx.doi.org/10.1161/JAHA.120.020215DOI Listing
July 2021

Fabrication of Biomolecule-Covalent-Organic-Framework Composites as Responsive Platforms for Smart Regulation of Fermentation Application.

ACS Appl Mater Interfaces 2021 Jul 1;13(27):32058-32066. Epub 2021 Jul 1.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, China.

Exploration of novel material platforms to protect biological preservatives and realize intelligent regulation during fermentation is of great significance in industry. Herein, we established an intelligent responsive platform by introducing antimicrobial biomolecules (nisin) into rationally designed covalent organic frameworks (COFs), resulting in a new type of "smart formulation", which could responsively inhibit microbial contamination and ensure the orderly progression of the fermentation process. The encapsulated biomolecules retained their activity while exhibiting enhanced stability and pH-responsive releasing process (100% bacteriostatic efficiency at a pH of 3), which can ingeniously adapt to the environmental variation during the fermentation process and smartly fulfill the regulation needs. Moreover, the [email protected] composites would not affect the fermentation strains. This study will pave a new avenue for the preparation of highly efficient and intelligent antimicrobial agents for the regulation of the fermentation process and play valuable roles in the drive toward green and sustainable biomanufacturing.
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http://dx.doi.org/10.1021/acsami.1c02120DOI Listing
July 2021

Recovery of a Far-Eastern Strain of Tick-Borne Encephalitis Virus with a Full-Length Infectious cDNA Clone.

Virol Sin 2021 Jun 30. Epub 2021 Jun 30.

CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

Tick-borne encephalitis virus (TBEV) is a pathogenic virus known to cause central nervous system (CNS) diseases in humans, and has become an increasing public health threat nowadays. The rates of TBEV infection in the endemic countries are increasing. However, there is no effective antiviral against the disease. This underscores the urgent need for tools to study the emergence and pathogenesis of TBEV and to accelerate the development of vaccines and antivirals. In this study, we reported an infectious cDNA clone of TBEV that was isolated in China (the WH2012 strain). A beta-globin intron was inserted in the coding region of nonstructural protein 1 (NS1) gene to improve the stability of viral genome in bacteria. In mammalian cells, the inserted intron was excised and spliced precisely, which did not lead to the generation of inserted mutants. High titers of infectious progeny viruses were generated after the transfection of the infectious clone. The cDNA-derived TBEV replicated efficiently, and caused typical cytopathic effect (CPE) and plaques in BHK-21 cells. In addition, the CPE and growth curve of cDNA-derived virus were similar to that of its parental isolate in cells. Together, we have constructed the first infectious TBEV cDNA clone in China, and the clone can be used to investigate the genetic determinants of TBEV virulence and disease pathogenesis, and to develop countermeasures against the virus.
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http://dx.doi.org/10.1007/s12250-021-00396-6DOI Listing
June 2021

Association of Obesity and Body Fat Percentage with Pubertal State in Six- to Nine-Year-Old Chinese Females.

Child Obes 2021 Jun 29. Epub 2021 Jun 29.

Department of Clinical Epidemiology and Biostatistics, Children Health Advocacy Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

An early trend in the mean age of pubertal onset appears in adolescents, but the association between body fat percentage (BF%) of children and precocious puberty is unclear. The aim of the study was to analyze the association of sexual development with BF% in girls. A total of 407 females were included in this cross-sectional study. BF% was measured by Inbody S10, International Obesity Task Force was used to judge overweight or obesity, and early puberty was defined as a younger age than the median age in each of the pubertal Tanner stages. Logistic regression analysis was used to test relationships between pubertal states and independent variables, including age, weight, waist circumference (WC), type of school, and residency. Females with early puberty exhibited higher anthropometry data (such as weight, BMI, BF%) than females with normal maturation ( < 0.001). Weight, BMI, WC, BF% residency, and school type were related to pubertal state ( < 0.001). Females with higher BF% were more likely to exhibit early puberty (odds ratio = 1.138, 95% confidence interval = 1.046-1.237). The students who lived in urban areas and studied in public schools had a lower risk of early puberty. Moreover, BF% continuously increased with age in 6- to 9-year-old girls. Females with higher BF% may be more likely to exhibit early puberty. In future studies, more research is needed to analyze this mechanism of how BF% influences puberty development.
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http://dx.doi.org/10.1089/chi.2020.0247DOI Listing
June 2021

A Rare Case of Nail Bed Foreign Body Granuloma with Malignant Dermoscopic Appearance.

Indian J Dermatol 2021 Mar-Apr;66(2):205-206

Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, China.

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http://dx.doi.org/10.4103/ijd.IJD_630_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208276PMC
June 2021

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.

Nat Commun 2021 06 28;12(1):3987. Epub 2021 Jun 28.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.
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http://dx.doi.org/10.1038/s41467-021-23899-yDOI Listing
June 2021

The role of lncRNA Meg3 in the proliferation of all-trans retinoic acid-treated mouse embryonic palate mesenchymal cells involves the Smad pathway.

Reprod Toxicol 2021 Jun 21;104:1-7. Epub 2021 Jun 21.

Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China; School of Public Health, Zhengzhou University, Zhengzhou, Henan, China. Electronic address:

Mesenchymal cell proliferation is critical for the growth of the palate shelf. All-trans retinoic acid (atRA), as well as pathways associated with TGF-β/Smad signaling, play crucial roles in the proliferation of mouse embryonic palate mesenchymal (MEPM) cells. We have found that MEPM-cell proliferation was regulated by atRA and exogenous TGF-β3 could significantly antagonize the atRA-mediated suppression of MEPM cell proliferation, which is closely associated with the regulation of TGF-β/Smad signaling pathway. The long non-coding RNA (lncRNA) MEG3 has been reported to activate TGF-β/Smad signaling, thereby regulating cellular proliferation, differentiation, and related processes. Here, we found that Meg3 expression increased significantly in atRA-treated MEPM cells while TGF-β3 treatment markedly inhibited Meg3 expression and antagonized the effect of atRA on Meg3. Moreover, Smad2 was found to interact directly with Meg3, and atRA treatment significantly enriched Meg3 in Smad2-immunoprecipitated samples. After Meg3 deletion, the effects of atRA on the proliferation of MEPM cells and TGF-β3-dependent protein expression were lost. Hence, we speculate that Meg3 has a role in the RA-induced suppression of MEPM cell proliferation by targeting Smad2 and thereby mediating TGF-β/Smad signaling inhibition.
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http://dx.doi.org/10.1016/j.reprotox.2021.06.011DOI Listing
June 2021

Genetic characterization and phylogenetic analysis of porcine epidemic diarrhea virus in Guangdong, China, between 2018 and 2019.

PLoS One 2021 24;16(6):e0253622. Epub 2021 Jun 24.

College of Life Science and Engineering, Foshan University, Foshan, Guangdong, China.

Porcine epidemic diarrhea virus (PEDV), a leading cause of piglet diarrhea outbreaks, poses a significant danger to the swine industry. The aim of this study was to investigate the epidemic characteristics of PEDV that was circulating in Guangdong province, one of China's major pig producing provinces. Clinical samples were collected from eight pig farms in Guangdong province between 2018 and 2019 and tested for the major porcine enteric pathogens, including PEDV, transmissible gastroenteritis virus (TGEV), Swine enteric coronavirus (SeCoV), Swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine deltacoronavirus (PDCoV), and porcine rotavirus (RV). As a result, only PEDV and RV were detected at a rate of 47.0% (16/34) and 18.6% (8/34), respectively. Coinfectoin with PEDV and RV occurred at a rate of PEDV 12.5% (2/16). Subsequently, the full-length S gene sequences of 13 PEDV strains were obtained, and phylogenetic analysis suggested the presence of GII-c group PEDV strains in this region (non-S-INDEL). Two novel common amino acid insertions (55T/IG56 and 551L) and one novel glycosylation site (1199G+) were detected when the CV777 and ZJ08 vaccine strains were compared. Furthermore, intragroup recombination events in the S gene regions 51-548 and 2478-4208 were observed in the PEDV strains studied. In summary, the observations provide current information on the incidence of viral agents causing swine diarrhea in southern China and detailed the genetic characteristics and evolutionary history of the dominant PEDV field strains. Our findings will aid in the development of an updated vaccine for the prevention and control of PEDV variant strains.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253622PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224968PMC
July 2021

Associations of Alcohol Consumption with Cardiovascular Disease-Related Proteomic Biomarkers: The Framingham Heart Study.

J Nutr 2021 Jun 22. Epub 2021 Jun 22.

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Background: Alcohol consumption and cardiovascular disease (CVD) have a complex relation.

Objectives: We examined the associations between alcohol consumption, fasting plasma proteins, and CVD risk.

Methods: We performed cross-sectional association analyses of alcohol consumption with 71 CVD-related plasma proteins, and also performed prospective association analyses of alcohol consumption and protein concentrations with 3 CVD risk factors (obesity, hypertension, and diabetes) in 6745 Framingham Heart Study (FHS) participants (mean age 49 y; 53% women).

Results: A unit increase in log10 transformed alcohol consumption (g/d) was associated with an increased risk of hypertension (HR = 1.14; 95% CI: 1.04, 1.26; P = 0.007), and decreased risks of obesity (HR = 0.80; 95% CI: 0.71, 0.91; P = 4.6 × 10-4) and diabetes (HR: 0.68; 95% CI: 0.58, 0.80; P = 5.1 × 10-6) in a median of 13-y (interquartile = 7, 14) of follow-up. We identified 43 alcohol-associated proteins in a discovery sample (n = 4348, false discovery rate <0.05) and 20 of them were significant (P <0.05/43) in an independent validation sample (n = 2397). Eighteen of the 20 proteins were inversely associated with alcohol consumption. Four of the 20 proteins demonstrated 3-way associations, as expected, with alcohol consumption and CVD risk factors. For example, a greater concentration of APOA1 was associated with higher alcohol consumption (P = 1.2 × 10-65), and it was also associated with a lower risk of diabetes (P = 8.5 × 10-6). However, several others showed unexpected 3-way associations.

Conclusions: We identified 20 alcohol-associated proteins in 6745 FHS samples. These alcohol-associated proteins demonstrated complex relations with the 3 CVD risk factors. Future studies with integration of more proteomic markers and larger sample size are warranted to unravel the complex relation between alcohol consumption and CVD risk.
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http://dx.doi.org/10.1093/jn/nxab186DOI Listing
June 2021

Schizophrenia Plays a Negative Role in the Pathological Development of Myocardial Infarction at Multiple Biological Levels.

Front Genet 2021 3;12:607690. Epub 2021 Jun 3.

The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

It has shown that schizophrenia (SCZ) is associated with a higher chance of myocardial infarction (MI) and increased mortality. However, the underlying mechanism is largely unknown. Here, we first constructed a literature-based genetic pathway linking SCZ and MI, and then we tested the expression levels of the genes involved in the pathway by a meta-analysis using nine gene expression datasets of MI. In addition, a literature-based data mining process was conducted to explore the connection between SCZ at different levels: small molecules, complex molecules, and functional classes. The genetic pathway revealed nine genes connecting SCZ and MI. Specifically, SCZ activates two promoters of MI (IL6 and CRP) and deactivates seven inhibitors of MI (ADIPOQ, SOD2, TXN, NGF, ADORA1, NOS1, and CTNNB1), suggesting that no protective role of SCZ in MI was detected. Meta-analysis showed that one promoter of MI (CRP) presented no significant increase, and six out of seven genetic inhibitors of MI demonstrated minor to moderately increased expression. Therefore, the elevation of CRP and inhibition of the six inhibitors of MI by SCZ could be critical pathways to promote MI. Nine other regulators of MI were influenced by SCZ, including two gene families (inflammatory cytokine and IL1 family), five small molecules (lipid peroxide, superoxide, ATP, ascorbic acid, melatonin, arachidonic acid), and two complexes (CaM kinase 2 and IL23). Our results suggested that SCZ promotes the development and progression of MI at different levels, including genes, small molecules, complex molecules, and functional classes.
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http://dx.doi.org/10.3389/fgene.2021.607690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211423PMC
June 2021

The Development and Validation of the Psychological Needs of Cancer Patients Scale.

Front Psychol 2021 3;12:658989. Epub 2021 Jun 3.

Department of Psychology, Chongqing University Cancer Hospital, Chongqing, China.

In the present research, the Psychological Needs of Cancer Patients Scale (PNCPS) was developed and validated. Based on Group 1 (400 cancer patients), the exploratory factor analysis identified a 23-item scale with six factors: value and esteem (five items, i.e., reconsider the meaning and purpose of life), independence and control (six items, i.e., private space), mental car (three items, i.e., vent negative emotions), disease care (three items, i.e., acquire knowledge about disease), belonging and companionship (three items, i.e., spend more time at home), and security (three items, i.e., living conditions be better). The structure identified with Group 1 was further tested, based on Group 2 (199 cancer patients), for reliability and validity. The results showed that PNCPS has a clear factor structure and good psychometric characteristics. By taking into account the cultural background of Chinese patients, this scale will advance the study of the psychological needs of those with malignant tumors and thus has a certain reference value for other countries.
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http://dx.doi.org/10.3389/fpsyg.2021.658989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209331PMC
June 2021

Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study.

World J Emerg Med 2021 ;12(3):185-191

Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Background: The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.

Methods: A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14 monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR).

Results: A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively.

Conclusions: Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188286PMC
January 2021

Electrolyte Concentration Regulation Boosting Zinc Storage Stability of High-Capacity KVO Cathode for Bendable Quasi-Solid-State Zinc Ion Batteries.

Nanomicro Lett 2021 Jan 4;13(1):34. Epub 2021 Jan 4.

School of Chemistry, Chemical Engineering and Life Science, and State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, 430070, People's Republic of China.

Vanadium-based cathodes have attracted great interest in aqueous zinc ion batteries (AZIBs) due to their large capacities, good rate performance and facile synthesis in large scale. However, their practical application is greatly hampered by vanadium dissolution issue in conventional dilute electrolytes. Herein, taking a new potassium vanadate KVO (KVO) cathode with large interlayer spacing (~ 0.95 nm) and high capacity as an example, we propose that the cycle life of vanadates can be greatly upgraded in AZIBs by regulating the concentration of ZnCl electrolyte, but with no need to approach "water-in-salt" threshold. With the optimized moderate concentration of 15 m ZnCl electrolyte, the KVO exhibits the best cycling stability with ~ 95.02% capacity retention after 1400 cycles. We further design a novel sodium carboxymethyl cellulose (CMC)-moderate concentration ZnCl gel electrolyte with high ionic conductivity of 10.08 mS cm for the first time and assemble a quasi-solid-state AZIB. This device is bendable with remarkable energy density (268.2 Wh kg), excellent stability (97.35% after 2800 cycles), low self-discharge rate, and good environmental (temperature, pressure) suitability, and is capable of powering small electronics. The device also exhibits good electrochemical performance with high KVO mass loading (5 and 10 mg cm). Our work sheds light on the feasibility of using moderately concentrated electrolyte to address the stability issue of aqueous soluble electrode materials.
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http://dx.doi.org/10.1007/s40820-020-00554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187517PMC
January 2021

Nitrogen influenced competition between the genders of  Salix rehderiana.

Tree Physiol 2021 Jun 17. Epub 2021 Jun 17.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.

Male and female willow plants show spatial segregation of genders along the environmental gradients. Skewed gender ratio of willows is not only related to altitude, but also to nutrient status and sexual competition, which can affect their growth and defense by altering secondary metabolite production. The relationship between metabolites and nutrients in the two genders of Salix rehderiana was explored in the Gongga Mountain. We found gender ratio was altered with a change in soil nitrogen (N) status; in the high N habitats, secondary metabolites accumulated in males. Furthermore, pot experiment was conducted to test the effect of nitrogen supply on gender competition in S. rehderiana. Sufficient N supply stimulated females to produce amino acids and carbon-containing secondary metabolites for maintaining their carbon-nitrogen balance, but extra nitrogen for males was used for growth to occupy more space. N supply induced foliar nutrient imbalances and growth of opportunistic species, allowing them to outcompete neighbors. Better carbon allocation and storage in male than female willows would benefit intersexual competitiveness of males if environment N increases. Competition between the genders has a significant correlation with skewed gender ratio, spatial separation and resource utilization. Female willows would suffer fiercer competition for space by males with the increased soil N, which would result in the gender ratio alteration. Therefore, gender ratio of willows is likely to convert to gender balance from female-biased with long-term N deposition in the future.
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http://dx.doi.org/10.1093/treephys/tpab083DOI Listing
June 2021

The novel FAT4 activator jujuboside A suppresses NSCLC tumorigenesis by activating HIPPO signaling and inhibiting YAP nuclear translocation.

Pharmacol Res 2021 Jun 9;170:105723. Epub 2021 Jun 9.

Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China; State Key Laboratory of Quality Research in Chinese Medicine/ Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), PR China. Electronic address:

FAT atypical cadherin 4 (FAT4) has been identified as a tumor suppressor in lung cancers. However, no agent for lung cancer treatment targeting FAT4 has been used in the clinic. Jujuboside A (JUA) is a major active compound in Semen Ziziphi Spinosae. Semen Ziziphi Spinosae is a traditional Chinese herbal medicine used clinically for tumor treatment to improve patients' quality of life. However, the anti-lung cancer activity and the underlying mechanisms of JUA are not yet fully understood. Here, we demonstrated the anti-lung cancer activity of JUA in two lung cancer mice models and three non-small cell lung cancer (NSCLC) cell lines, and further illustrated its underlying mechanisms. JUA suppressed the occurrence and development of lung cancer and extended mice survival in vivo, and suppressed NSCLC cell activities through cell cycle arrest, proliferation suppression, stemness inhibition and senescence promotion. Moreover, JUA directly bound with and activated FAT4, subsequently activating FAT4-HIPPO signaling and inhibiting YAP nuclear translocation. Knockdown of FAT4 diminished JUA's effects on HIPPO signaling, YAP nuclear translocation, cell proliferation and cellular senescence. In conclusion, JUA significantly suppressed NSCLC tumorigenesis by regulating FAT4-HIPPO-YAP signaling. Our findings suggest that JUA is a novel FAT4 activator that can be developed as a promising NSCLC therapeutic agent targeting the FAT4-HIPPO-YAP pathway.
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http://dx.doi.org/10.1016/j.phrs.2021.105723DOI Listing
June 2021

The diagnostic value of CEA for lung cancer-related malignant pleural effusion in China: a meta-analysis.

Expert Rev Respir Med 2021 Jun 24:1-10. Epub 2021 Jun 24.

Department of Pathology, Jiangdu People's Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, China.

: To accurately evaluate the diagnostic value of carcinoembryonic antigen (CEA) for malignant pleural effusion associated with lung cancer in the Chinese population.: Three English databases, PubMed, Embase and Web of Science, and two Chinese databases, China National Knowledge Infrastructure (CNKI) and Wanfang Data, up to 5 November 2020, were searched. The literature on the diagnosis of lung cancer-related malignant pleural effusion by CEA in the Chinese population were collected. The data was analyzed by Stata15.0 software.: A total of 15 studies were included in the meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio were 0.80 (95% CI: 0.74-0.84), 0.92 (95% CI: 0.89-0.95), 10.46 (95% CI: 7.29-15.00), 0.22 (95% CI: 0.17-0.28), 47.26 (95% CI: 28.84-77.44), respectively . The area under the receiver operating characteristic curve was 0.93 (95% CI: 0.91-0.95). No significant publication bias was found ( > 0.05): CEA has anexcellent diagnostic value for patients with lung cancer-related malignant pleural effusion in the Chinese population.
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http://dx.doi.org/10.1080/17476348.2021.1941885DOI Listing
June 2021