Publications by authors named "Qiang Zhou"

820 Publications

Simultaneous Pickup and Delivery Traveling Salesman Problem considering the Express Lockers Using Attention Route Planning Network.

Comput Intell Neurosci 2021 22;2021:5590758. Epub 2021 May 22.

Institute of Information Engineering, Chinese Academy of Sciences, Beijing100195, China.

This paper presents a simultaneous pickup and delivery route designing model, which considers the use of express lockers. Unlike the traditional traveling salesman problem (TSP), this model analyzes the scenario that a courier serves a neighborhood with multiple trips. Considering the locker and vehicle capacity, the total cost is constituted of back order, lost sale, and traveling time. We aim to minimize the total cost when satisfying all requests. A modified deep Q-learning network is designed to get the optimal results from our model, leveraging masked multi-head attention to select the courier paths. Our algorithm outperforms other stochastic optimization methods with better optimal solutions and () computational time in evaluation processes. The experiment has shown that reinforcement learning is a better choice than traditional stochastic optimization methods, consuming less power and time during evaluation processes, which indicates that this approach fits better for large-scale data and broad deployment.
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http://dx.doi.org/10.1155/2021/5590758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166504PMC
May 2021

SMARCC2 combined with c‑Myc inhibits the migration and invasion of glioma cells via modulation of the Wnt/β‑catenin signaling pathway.

Mol Med Rep 2021 Aug 3;24(2). Epub 2021 Jun 3.

Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Glioma is the most common type of central nervous system tumor. SWItch/sucrose non‑fermentable (SWI/SNF) is a tumor suppressor that serves an important role in epithelial‑mesenchymal transition (EMT). The present study aimed to identify key molecules involved in the EMT process. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) is mutated in and its expression is low in multiple types of cancer. SMARCC2 is the core subunit of the chromatin‑remodeling complex, SWI/SNF. Relative mRNA SMARCC2 expression levels in human glioma tissue were analyzed via reverse transcription‑quantitative PCR, whereas the protein expression levels were determined via immunohistochemistry staining. SMARCC2 expression was knocked down in glioma cells using small interfering RNA (si) and overexpressed by infection with adenovirus vectors carrying SMARCC2 cDNA. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Subsequently, immunofluorescence and western blotting were performed to analyze the expression levels of the oncogene c‑Myc, which is associated with SMARCC2. SMARCC2 combines with C‑MYC to downregulate its expression. Consistent with the results of the bioinformatics analysis, which revealed that the upregulated expression levels of SMARCC2 were associated with a more favorable prognosis in patients with glioma, the mRNA and protein expression levels of SMARCC2 were significantly upregulated in low‑grade glioma tissues compared with high‑grade glioma tissues. The results of the wound healing assay demonstrated that cell migration was significantly increased in the siSMARCC2‑1/3 groups compared with the negative control (NC) group. By contrast, the migratory ability of cells was significantly reduced following transduction with adenovirus overexpressing SMARCC2, which upregulated the expression of SMARCC2, compared with the lentiviral vector‑non‑specific control (LVS‑NC) group. The Transwell assay results further showed that SMARCC2 overexpression significantly inhibited the migratory and invasive abilities of U87MG and LN229 cells compared with the LVS‑NC group. Co‑immunoprecipitation assays were subsequently conducted to validate the binding of SMARCC2 and c‑Myc; the results demonstrated that the expression of c‑Myc was downregulated in adenovirus‑transfected cells compared with LVS‑NC‑transfected cells. The results of the western blotting experiments demonstrated that the expression levels of N‑cadherin, vimentin, snail family transcriptional repressor 1 and β‑catenin were notably downregulated, whereas the expression levels of T‑cadherin were markedly upregulated in cell lines stably overexpressing SMARCC2 compared with the LVS‑NC group. In conclusion, the results of the present study suggested that SMARCC2 may inhibit Wnt/β‑catenin signaling by regulating c‑Myc expression in glioma. SMARCC2 regulates the EMT status of the glioblastoma cell line by mediating the expression of the oncogene C‑MYC to inhibit its migration and invasion ability. Thus, SMARCC2 may function as a tumor suppressor or oncogene by regulating associated oncogenes or tumor suppressor genes.
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http://dx.doi.org/10.3892/mmr.2021.12190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185515PMC
August 2021

Elevated activity in the dorsal dentate gyrus reduces expression of fear memory after fear extinction training.

J Psychiatry Neurosci 2021 06 2;46(3):E390-E401. Epub 2021 Jun 2.

From the Peking University, Shenzhen Graduate School, School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Shenzhen 518055, Peoples R China (Zhang, Wang, Zhou); the Precision Medicine Centre, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China (Ju); and the Pediatric Neurology, Shenzhen Children’s Hospital, Shenzhen, 518038, China (Zhang, Liao).

Background: Effectively reducing the expression of certain aversive memories (fear or trauma memories) with extinction training is generally viewed to be therapeutically important. A deeper understanding of the biological basis for a more effective extinction process is also of high scientific importance.

Methods: Our study involved intraventricular injection or local injection into the dorsal dentate gyrus of anti-neuregulin 1 antibodies (anti-NRG1) before fear extinction training, followed by testing the expression of fear memory 24 hours afterward or 9 days later. We used local injection of chemogenetic or optogenetic viruses into the dorsal dentate gyrus to manipulate the activity of the dorsal dentate gyrus and test the expression of fear memory. We also examined the effect of deep brain stimulation in the dorsal dentate gyrus on the expression of fear memory.

Results: Mice that received intraventricular injection with anti-NRG1 antibodies exhibited lower expression of fear memory and increased density of activated excitatory neurons in the dorsal dentate gyrus. Injection of anti-NRG1 antibodies directly into the dorsal dentate gyrus also led to lower expression of fear memory and more activated neurons in the dorsal dentate gyrus. Inhibiting the activity of dorsal dentate gyrus excitatory neurons using an inhibitory designer receptor exclusively activated by designer drugs (DREADD) eliminated the effects of the anti-NRG1 antibodies. Enhancing the activity of the dorsal dentate gyrus with an excitatory DREADD or optogenetic stimulation resulted in lower expression of fear memory in mice that did not receive infusion of anti-NRG1 antibodies. Deep brain stimulation in the dorsal dentate gyrus effectively suppressed expression of fear memory, both during and after fear extinction training.

Limitations: The mechanism for the contribution of the dorsal dentate gyrus to the expression of fear memory needs further exploration.

Conclusion: Activation of the dorsal dentate gyrus may play an important role in modulating the expression of fear memory; its potential use in fear memory extinction is worthy of further exploration.
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http://dx.doi.org/10.1503/jpn.200151DOI Listing
June 2021

SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2.

Immunity 2021 06 9;54(6):1304-1319.e9. Epub 2021 May 9.

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.

Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.
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http://dx.doi.org/10.1016/j.immuni.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106883PMC
June 2021

Circular RNA circ_0006948 Promotes Esophageal Squamous Cell Carcinoma Progression by Regulating microRNA-3612/LASP1 Axis.

Dig Dis Sci 2021 May 22. Epub 2021 May 22.

Department of Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, No. 358 Datong Road, Pudong New District, Shanghai, 200137, China.

Background: Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignancy worldwide. Circular RNAs (circRNAs) circ_0006948 is reported to be upregulated in ESCC cells.

Aims: This study is designed to explore the role and mechanism of circ_0006948 in ESCC progression.

Methods: Circ_0006948, linear FNDC3B, microRNA-3612 (miR-3612), and LIM and SH3 protein 1 (LASP1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, colony number, migration, invasion, and apoptosis were examined by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. Glucose consumption, lactate production, and ATP level were measured by the corresponding kits. Protein levels of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), and LASP1 were assessed by western blot assay. The cytoplasmic localization of circ_0006948 was identified by the subcellular fractionation assay. The binding relationship between miR-3612 and circ_0006948 or LASP1 was predicted by starBase or TargetScan and then verified by a dual-luciferase reporter assay. The biological role of circ_0006948 on ESCC tumor growth was examined by the xenograft tumor model in vivo.

Results: Circ_0006948 and LASP1 were increased, and miR-3612 was decreased in ESCC tissues and cells. Furthermore, circ_0006948 knockdown could suppress cell viability, colony number, migration, invasion, glycolysis, and boost apoptosis in ESCC cells. Mechanically, circ_0006948 could act as a sponge of miR-3612 to regulate LASP1 expression. In addition, circ_0006948 silencing inhibited ESCC tumor growth in vivo.

Conclusion: Circ_0006948 boosted ESCC progression partly by regulating the miR-3612/LASP1 axis, providing an underlying therapeutic target for the ESCC treatment.
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http://dx.doi.org/10.1007/s10620-021-07057-4DOI Listing
May 2021

A simple and rapid method for fish sex identification based on recombinase-aided amplification and its use in Cynoglossus semilaevis.

Sci Rep 2021 May 17;11(1):10429. Epub 2021 May 17.

Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources, College of Life Sciences, Anhui Normal University, Wuhu, 241000, China.

Fish sex identification is a basic technique of great importance for both fish genetic studies and fisheries. Due to the sexual reversal phenomenon in many fish species, a simple and rapid molecular identification method for fish genetic sex is urgently needed to suit versatile detection scenarios, such as point-of-need applications. In this study, we took Cynoglossus semilaevis as an example, established a recombinase-aided amplification (RAA)-based method for sex identification, and combined the RAA-detection with two result visualization approaches with distinct features, capillary electrophoresis (CE) and lateral flow dipstick (LFD). Specific primers and probe were designed to specifically detect the sex chromosome W of C. semilaevis in order to distinguish the genetic sex between males, pseudo-males and females. To evaluate the performance of our methods, the genetic sex for twenty-eight males, sixty-eight pseudo-males and fifty-four females were examined with the RAA-based method and classical PCR-based genotyping method, demonstrating the consistent results of sex identification between both methods. The RAA-LFD method is operationally simple, rapid (~ 30 min) and holds great potential for point-of-need applications of fish sex identification, including fishery fields. The method presented here could be effective for identifying fish gender with the ZW karyotype.
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http://dx.doi.org/10.1038/s41598-021-89571-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128863PMC
May 2021

Wrinkle and near-resonance effects on the vibrational and electronic properties in compressed monolayer MoSe.

Phys Chem Chem Phys 2021 May 13;23(20):11709-11716. Epub 2021 May 13.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun, 130012, China.

Pressure has been considered as an effective technique to modulate the structural, electronic, and optical properties of transition metal dichalcogenide (TMDs) materials. Here, by performing in situ high pressure Raman, photoluminescence (PL) and absorption measurements, we systematically investigated the vibrational and electronic properties evolution of monolayer MoSe grown on a SiO/Si substrate under high pressure. When the pressure increased up to 4.84 GPa, an unexpected phonon mode at 367 cm appeared, which was identified as the Raman-inactive A'' mode and was activated under high pressure. Combined with the analysis of absorption spectroscopy, this phenomenon can be attributed to the pressure-induced wrinkle and near-resonance effects in compressed monolayer MoSe. Subsequently, A' split into two peaks after 7.44 GPa, providing further distinct evidence for the pressure-induced wrinkle effect in compressed monolayer MoSe. Moreover, this wrinkle effect can also lead to a rapid quenching of photoluminescence in monolayer MoSe. These results suggest that the substrate plays an important role in determining the vibrational and electronic properties of compressed monolayer MoSe, and can provide valuable information on the electronic and optoelectronic applications of monolayer MoSe under extreme conditions.
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http://dx.doi.org/10.1039/d0cp06283aDOI Listing
May 2021

Influence of psychological stress and coping styles in the professional identity of undergraduate nursing students after the outbreak of COVID-19: A cross-sectional study in China.

Nurs Open 2021 May 7. Epub 2021 May 7.

College of Nursing, Hebei Medical University, Shijiazhuang, 050017, China.

Aim: To investigate the influencing factors in professional identity of undergraduate nursing students after the outbreak of COVID-19.

Design: Cross-sectional study.

Methods: The study covered 2,999 nursing students in six undergraduate nursing schools. Several self-report questionnaires were used to collect the general information, psychological stress, coping styles and professional identity of the undergraduate nursing students.

Results: The overall average score of the professional identity of nursing students (3.67 ± 0.51) has increased significantly after the outbreak of COVID-19. The professional identity of the undergraduate nursing students was negatively correlated with psychological stress (r = -0.23, p < .001), expectation (r = -0.12, p < .001) and avoidance (r = -0.16, p < .001), but was positively correlated with solving problems (r = 0.18, p < .001) and seeking support (r = 0.12, p < .001). Academic performance, positions, grades, reasons for choosing a nursing profession, parents or relatives engaged in nursing work and the risk degree of residence were the factors influencing the professional identity score of undergraduate nursing students' (p < .001).
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http://dx.doi.org/10.1002/nop2.902DOI Listing
May 2021

Current Status of Ultrasound in Acute Rejection After Renal Transplantation: A Review with a Focus on Contrast-Enhanced Ultrasound.

Ann Transplant 2021 May 4;26:e929729. Epub 2021 May 4.

Department of Nephrology, Chongqing Southwest Hospital, Chongqing, China (mainland).

Renal transplantation has developed into the best treatment for end-stage renal disease, but severe cases can even lead to loss of renal allograft function due to rejection and complications caused by surgical procedures. If a series of postoperative complications can be reduced or even avoided, the quality of life of recipients will be significantly improved. Acute rejection in a transplanted kidney is one of the main complications after renal transplantation. Early detection and diagnosis will significantly help the prognosis of transplanted kidney patients. As a seminal morphological and hemodynamic examination method, ultrasound can monitor the tissue structure and arteriovenous blood flow of the transplanted kidney, providing information on the transplanted kidney's gross shape and blood perfusion. Ultrasound is a commonly used detection method after renal transplantation. At present, two-dimensional ultrasound, color Doppler ultrasound, three-dimensional ultrasound, and contrast-enhanced ultrasound have been applied in the monitoring of complications after renal transplantation. Contrast-enhanced ultrasound, as a non-invasive, radiation-free, and easy to perform examination technique, can qualitatively and quantitatively evaluate the microcirculatory blood perfusion of the transplanted kidney. It can reflect the function of the transplanted kidney more objectively and sensitively. In recent years, contrast-enhanced ultrasound has attracted attention as a new technology that can quantitatively monitor the transplanted kidney's microcirculation perfusion. A large number of studies have shown that contrast-enhanced ultrasound has unique advantages in monitoring acute rejection after renal transplantation compared with other imaging methods, providing a reliable basis for clinical intervention. This article reviews the current status of and recent research on contrast-enhanced ultrasound in acute rejection after renal transplantation.
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http://dx.doi.org/10.12659/AOT.929729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106257PMC
May 2021

Altered Relationship Between Parvalbumin and Perineuronal Nets in an Autism Model.

Front Mol Neurosci 2021 12;14:597812. Epub 2021 Apr 12.

Key Laboratory of Chemical Genome, State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, China.

Altered function or presence of inhibitory neurons is documented in autism spectrum disorders (ASD), but the mechanism underlying this alternation is poorly understood. One major subtype of inhibitory neurons altered is the parvalbumin (PV)-containing neurons with reduced density and intensity in ASD patients and model mice. A subpopulation of PV neurons expresses perineuronal nets (PNN). To better understand whether the relationship between PV and PNN is altered in ASD, we measured quantitatively the intensities of PV and PNN in single PV neurons in the prelimbic prefrontal cortex (PrL-PFC) of a valproic acid (VPA) model of ASD at different ages. We found a decreased PV intensity but increased PNN intensity in VPA mice. The relationship between PV and PNN intensities is altered in VPA mice, likely due to an "abnormal" subpopulation of neurons with an altered PV-PNN relationship. Furthermore, reducing PNN level using injection of chondroitinase ABC corrects the PV expression in adult VPA mice. We suggest that the interaction between PV and PNN is disrupted in PV neurons in VPA mice which may contribute to the pathology in ASD.
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http://dx.doi.org/10.3389/fnmol.2021.597812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072465PMC
April 2021

[Application of Iron and Sulfate-Modified Biochar in Phosphorus Removal from Water].

Huan Jing Ke Xue 2021 May;42(5):2313-2323

School of Environmental and Municipal Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China.

The excessive discharge of phosphate into natural water has caused serious environmental problems. Adsorption is an efficient technology for phosphorus removal from water. In this study, a novel biochar modified by chitosan, ferrous sulfate, and sodium sulfide was synthesized and performed well in phosphorus adsorption. The results of batch experiments showed that the optimum synthesized composite could adsorb 49.32 mg·g of phosphate at 298 K. Meanwhile, the simulation results showed better fitting with the pseudo-second-order model and Langmuir model. The adsorption rate was dominated by three-dimensional diffusion within the inner pores. The adsorption process was defined as physic/chemisorption, while the adsorption mechanism was concluded to be electrostatic adsorption, porous filling, surface chemical precipitation, hydrogen binding, and the ligand effect. This study showed that the composite is effective in phosphorus removal from water, and we anticipate that our research will offer guidelines for adsorbent design and reveal the adsorption mechanism.
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http://dx.doi.org/10.13227/j.hjkx.202008302DOI Listing
May 2021

Down-regulation of miR-219-5p increase the risk of cancer-related mortality in patients with prostate cancer.

Postgrad Med J 2021 Apr 20. Epub 2021 Apr 20.

Department of Oncology, Suining Central Hospital, Suining, China

Introduction: Prostate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear.

Methods: We retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model's accuracy.

Results: Of the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate's weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death's risk, with a corrected C-index of 0.778.

Conclusions: miR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.
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http://dx.doi.org/10.1136/postgradmedj-2021-139981DOI Listing
April 2021

A novel urine cell-free DNA preservation solution and its application in kidney transplantation.

Nephrology (Carlton) 2021 Apr 18. Epub 2021 Apr 18.

Biostatistics, R&D, AlloDx Biotech (Shanghai), Co., Ltd, Shanghai, China.

Aim: Urine cell-free DNA (cfDNA) is a new type of liquid biopsy biomarker used in tumours and allograft injury detection but is highly susceptible to degradation by the high nuclease activity of urine. This study presents a newly developed urine cfDNA preservation solution (AlloU), efficient for examining allograft injury in kidney transplant recipients (KTx).

Methods: We established urine-preserve solution called AlloU based on the response-surface methodology, with two commercial collection reagents (Streck and K2 EDTA preservation solution) included for analysis. A total of 120 urine samples from KTx patients, including morning, nocturnal and random urine from specific storage time were subjected to investigation. The urine total cfDNA concentration was quantified by fluorometry, fragment distribution was analysed by qPCR, and donor-derived cfDNA (ddcfDNA) was detected by next-generation sequencing.

Results: Urine total cfDNA concentration and fragment size of samples preserved with AlloU and Streck did not change significantly within 5 days whereas the ddcfDNA also did not change significantly within 7 days. However, compared with EDTA, the total cfDNA concentration increased significantly on the third day. When compare with different urine types, it was found that samples preserved with AlloU showed no significant differences in total cfDNA concentration, fragment size, and ddcfDNA concentration, however, the SD for morning urine was significantly smaller in total cfDNA and ddcfDNA concentration.

Conclusion: To the best of our knowledge, this is the first report to verify the dynamics of urine cfDNA in KTx, especially in the analysis impact of different urine types on cfDNA detection.
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http://dx.doi.org/10.1111/nep.13884DOI Listing
April 2021

Flower Development of Heterodichogamous (Juglandaceae).

Front Plant Sci 2021 30;12:541163. Epub 2021 Mar 30.

College of Forestry, Shenyang Agricultural University, Shenyang, China.

is a monoecious heterodichogamous species with protogynous and protandrous mating strategies that occur at a 1:1 ratio and are randomly distributed in the population. The inconsistent male and female flowering periods of the same mating type result in an imbalance of the ratio of male and female flowers, contributing to the low yield of this species. However, little more is known about its floral development. Following three consecutive years of observations, histological analysis, and scanning electron microscopy, we found that the morphological and anatomical development of the male and female flowers were synchronous. The male floral morphological development of . was divided into seven phases, while that of the female flower was nine. Four stages were shared between the male and female flower's anatomical development. Our findings indicate that there was minimal overlap between sexual functions within the same mating type, guaranteeing synchronization, mutual non-interference, outcrossing, and avoidance of self-fertilization. These results provide a theoretical basis for the improvement of fruit yield and quality through the reasonable allocation of protogynous and protandrous individuals in a population, and for artificial pollination control. Further, these findings lay a foundation for further research on the genetic mechanisms and environmental effects on flower development of heterodichogamous . .
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http://dx.doi.org/10.3389/fpls.2021.541163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042317PMC
March 2021

Silk films with nanotopography and extracellular proteins enhance corneal epithelial wound healing.

Sci Rep 2021 Apr 14;11(1):8168. Epub 2021 Apr 14.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor Street, MC648, Chicago, IL, 60612, USA.

Corneal wound healing depends on extracellular matrix (ECM) and topographical cues that modulate migration and proliferation of regenerating cells. In our study, silk films with either flat or nanotopography patterned parallel ridge widths of 2000, 1000, 800 nm surfaces were combined with ECMs which include collagen type I (collagen I), fibronectin, laminin, and Poly-D-Lysine to accelerate corneal wound healing. Silk films with 800 nm ridge width provided better cell spreading and wound recovery than other size topographies. Coating 800 nm patterned silk films with collagen I proves to optimally further increased mouse and rabbit corneal epithelial cells growth and wound recovery. This enhanced cellular response correlated with redistribution and increase in size and total amount of focal adhesion. Transcriptomics and signaling pathway analysis suggested that silk topography regulates cell behaviors via actin nucleation ARP-WASP complex pathway, which regulate filopodia formation. This mechanism was further explored and inhibition of Cdc42, a key protein in this pathway, delayed wound healing and decreased the length, density, and alignment of filopodia. Inhibition of Cdc42 in vivo resulted in delayed re-epithelization of injured corneas. We conclude that silk film nanotopography in combination with collagen I constitutes a better substrate for corneal wound repair than either nanotopography or ECM alone.
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http://dx.doi.org/10.1038/s41598-021-87658-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046786PMC
April 2021

A stepped wedge cluster randomized control trial to evaluate the implementation and effectiveness of optimized initiatives in improving quality of care for ST segment elevation myocardial infarction in response to the COVID-19 outbreak.

Implement Sci 2021 04 12;16(1):38. Epub 2021 Apr 12.

Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China.

Background: The National Chest Pain Center Accreditation Program (CHANGE) is the first hospital-based, multifaceted, nationwide quality improvement (QI) initiative, to monitor and improve the quality of the ST segment elevation myocardial infarction (STEMI) care in China. The QI initiatives, as implementation strategies, include a bundle of evidence-based interventions adapted for implementation in China. During the pandemic of coronavirus disease 2019 (COVID-19), fear of infection with severe acute respiratory syndrome coronavirus 2, national lockdowns, and altered health care priorities have highlighted the program's importance in improving STEMI care quality. This study aims to minimize the adverse impact of the COVID-19 pandemic on the quality of STEMI care, by developing interventions that optimize the QI initiatives, implementing and evaluating the optimized QI initiatives, and developing scale-up activities of the optimized QI initiatives in response to COVID-19 and other public health emergencies.

Methods: A stepped wedge cluster randomized control trial will be conducted in three selected cities of China: Wuhan, Suzhou, and Shenzhen. Two districts have been randomly selected in each city, yielding a total of 24 registered hospitals. This study will conduct a rollout in these hospitals every 3 months. The 24 hospitals will be randomly assigned to four clusters, and each cluster will commence the intervention (optimized QI initiatives) at one of the four steps. We will conduct hospital-based assessments, questionnaire surveys among health care providers, community-based household surveys, and key informant interviews during the trial. All outcome measures will be organized using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, including implementation outcomes, service outcomes (e.g., treatment time), and patient outcomes (e.g., in-hospital mortality and 1-year complication). The Consolidated Framework for Implementation Research framework will be used to identify factors that influence implementation of the optimized QI interventions.

Discussion: The study findings could be translated into a systematic solution to implementing QI initiatives in response to COVID-19 and future potential major public health emergencies. Such actionable knowledge is critical for implementors of scale-up activities in low- and middle-income settings.

Trial Registration: ChiCTR 2100043319 . Registered on 10 February 2021.
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http://dx.doi.org/10.1186/s13012-021-01107-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040354PMC
April 2021

Optimal pH shift of the NADH oxidase from Lactobacillus rhamnosus with a single mutation.

Biotechnol Lett 2021 Jul 12;43(7):1413-1420. Epub 2021 Apr 12.

School of Pharmacy, Jiangsu University, Zhenjiang, 212013, People's Republic of China.

Objective: To improve the activity of a water-forming NADH oxidase from Lactobacillus rhamnosus under neutral or alkaline pH for coupling NAD-dependent dehydrogenases with an alkaline optimal pH.

Results: The water-forming NADH oxidase from Lactobacillus rhamnosus was engineered by replacing the aspartic acid or glutamic acid with arginine on the surface. The mutant D251R improved the activity with a 112%, 111%, and 244% relative activity to the wild-type at pH 6.5, pH 7.0, and pH 7.5, respectively. Docking substrate into the D251R mutant reveals that the NADH is access to the substrate-binding site with a larger substrate loop due to the enhanced electrostatic repulsion between ARG-251 and ARG-243. In the D251R-NADH complex, the carboxyl of NADH additionally forms two hydrogen bonds (2.6 and 2.9 Å) with G154 due to the changed interaction of substrate and the residues in the catalytic sites, and the hydrogen bond with the oxygen of carbonyl in P295 is shortened from 2.9 to 2.0 Å, which could account for the enhanced specific activity.

Conclusions: The D251R mutant displayed higher catalytic activity than the wild-type in the pH range 6.5-7.5, and further insight into those shorter and newly formed hydrogen bonds in substrate docking analysis could account for the higher bind affinity and catalytic efficiency of D251R mutant.
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http://dx.doi.org/10.1007/s10529-021-03129-7DOI Listing
July 2021

Development and validation of a nomogram combining hematological and imaging features for preoperative prediction of microvascular invasion in hepatocellular carcinoma patients.

Ann Transl Med 2021 Mar;9(5):402

Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.

Background: Microvascular invasion (MVI) is a significant hazard factor that influences the recurrence and survival of hepatocellular carcinoma (HCC) patients after undergoing hepatectomy. This study aimed to develop and validate a nomogram that combines hematological and imaging features of HCC patients to preoperatively predict MVI, and investigate the effect of wide resection margin (≥1 cm) on the prognosis of MVI-positive HCC patients.

Methods: A total of 709 HCC patients who underwent hepatectomy at the Liver Cancer Institute of Zhongshan Hospital, Fudan University between June 1, 2015 and December 30, 2016 were included in this study and divided into training (496 patients) and validation cohort (213 patients). Least absolute shrinkage and selection operator (Lasso) regression and multivariable logistic regression were used for variables' selection and development of the predictive model. The model was presented as a nomogram, and its performance was assessed in terms of discrimination, calibration and clinical usefulness.

Results: Independent prognostic factors such as alkaline phosphatase (ALP, >125 U/L), alpha-fetoprotein (AFP, within 20-400 or >400 ng/mL), protein induced by vitamin K absence-II (PVIKA-II, within 40-400 or >400 mAU/mL), tumor number, diameter, pseudo-capsule, tumor growth pattern and intratumor hemorrhage were incorporated in the nomogram. The model showed good discrimination and calibration, with a concordance index (0.82, 95% CI, 0.782-0.857) in the training cohort and C-index (0.80, 95% CI, 0.772-0.837) in the validation cohort. Decision curve analysis (DCA) also showed that this model is clinically useful. Moreover, HCC patients with wide resection margin had a significantly lower 3-year recurrence rate than those with narrower resection margin (0.5-1 cm).

Conclusions: This study presents an optimal model for preoperative prediction of MVI and shows that wide resection margin for MVI-positive HCC patients has a better prognosis. This model can help surgeons choose the best treatment options for HCC patients before and after the operation.
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http://dx.doi.org/10.21037/atm-20-4695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033313PMC
March 2021

Occupational Burnout Among Frontline Health Professionals in a High-Risk Area During the COVID-19 Outbreak: A Structural Equation Model.

Front Psychiatry 2021 26;12:575005. Epub 2021 Mar 26.

Department of Psychiatry, Hunan Medical Center for Mental Health, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.

The outbreak of coronavirus disease 2019 (COVID-19) resulted in a substantial workload and stress for frontline health professionals in high-risk areas. Little research has investigated the mechanism of occupational burnout among the frontline health professionals located in the center of the epidemic in Wuhan, China. A total of 199 frontline health professionals from Wuhan Jinyintan Hospital completed the cross-sectional survey. Mechanisms of occupational burnout (according to the Maslach Burnout Inventory-General Survey, MBI-GS) among the health professionals in Jinyintan Hospital during the COVID-19 outbreak were examined using a structural equation model (SEM). The levels of the three burnout dimensions (emotional exhaustion, cynicism, and professional efficacy) were high at 34.2, 50.8, and 35.2%, respectively. Frontline health professionals in this stressful period reported significantly greater emotional exhaustion ( < 0.001) and job-related cynicism ( < 0.001), but no significant difference in professional efficacy ( = 0.449), when compared to employees in a large multinational company. The SEM results revealed that both acute stress symptoms and psychosomatic symptoms significantly predicted the emotional exhaustion and occupation cynicism dimensions of burnout. The study reveals the occupational burnout mechanism of frontline health professionals during the COVID-19 peak at the time of the outbreak. This study provides an important contribution to understanding the future psychological interventions necessary for frontline health professionals during an epidemic crisis.
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http://dx.doi.org/10.3389/fpsyt.2021.575005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032859PMC
March 2021

Development and Validation of a Metabolic Gene-Based Prognostic Signature for Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 29;8:193-209. Epub 2021 Mar 29.

Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with great variation in prognosis among individuals. Changes in metabolism influence disease progression and clinical outcomes. The objective of this study was to determine the overall survival (OS) risk of HCC patients from a metabolic perspective.

Patients And Methods: The model was constructed using the least absolute shrinkage and selection operator (LASSO) COX regression based on The Cancer Genome Atlas (TCGA, n=342) dataset. The International Cancer Genome Consortium (ICGC, n=232), GSE14520 (n=242) datasets, and a clinical cohort (n=64) were then used to assess the prognostic value of the signature.

Results: A 10 metabolic gene-based signature was constructed and verified as a robust and independent prognostic classifier in public and real-world validation cohorts. Meanwhile, the signature enabled the identification of HCC molecular subtypes, yielding an AUC value of 0.678 [95% CI: 0.592-0.763]. Besides, the signature was associated with metabolic processes like glycolysis, supported by a clear correlation between the risk score and expression of rate-limiting enzymes. Furthermore, high-risk tumor was likely to have a high tumor infiltration status of immunosuppressive cells, as well as elevated expression of some immune checkpoint molecules. For final clinical translation, a nomogram integrating the signature and tumor stage was established, and showed improved predictive accuracy of 3- and 5-year OS and brought more net benefit to patients.

Conclusion: We developed a prognostic signature based on 10 metabolic genes, which has proven to be an independent and reliable prognostic predictor for HCC and reflects the metabolic and immune characteristics of tumors.
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http://dx.doi.org/10.2147/JHC.S300633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018394PMC
March 2021

Complete chloroplast genome of D.G. Zhang, Ying Liu & Q. E. Yang (Asteraceae), a narrow endemic species in Wuling Mountain Region, China.

Mitochondrial DNA B Resour 2021 Mar 18;6(3):983-984. Epub 2021 Mar 18.

Key Laboratory of Plant Resources Conservation and Utilization, Jishou University, Jishou, Hunan, China.

The first complete chloroplast genome (cp) of D.G. Zhang, Ying Liu & Q. E. Yang (Asteraceae) was sequenced and assembled in this study. The cp genome was 151,257 bp in length, including a large single-copy(LSC) region of 83,373 bp, a small single-copy (SSC) region of 18,178 bp, and a pair of inverted repeat (IR) regions of 24,853 bp each. These sequences encoded 134 genes, including 89 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic analysis based on 18 complete cp sequences revealed that was closely related to
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http://dx.doi.org/10.1080/23802359.2021.1891981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995908PMC
March 2021

Quiescin sulfhydryl oxidase 1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by driving EGFR endosomal trafficking and inhibiting NRF2 activation.

Redox Biol 2021 May 13;41:101942. Epub 2021 Mar 13.

Liver Cancer Institute & Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis & Cancer Invasion, Fudan University & Ministry of Education, Shanghai, China. Electronic address:

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), but its clinical effects are still limited. In this study we identify Quiescin sulfhydryl oxidase 1 (QSOX1) acting as a cellular pro-oxidant, specifically in the context of sorafenib treatment of HCC. QSOX1 disrupts redox homoeostasis and sensitizes HCC cells to oxidative stress by inhibiting activation of the master antioxidant transcription factor NRF2. A negative correlation between QSOX1 and NRF2 expression was validated in tumor tissues from 151 HCC patients. Mechanistically, QSOX1 restrains EGF-induced EGFR activation by promoting ubiquitination-mediated degradation of EGFR and accelerating its intracellular endosomal trafficking, leading to suppression of NRF2 activity. Additionally, QSOX1 potentiates sorafenib-induced ferroptosis by suppressing NRF2 in vitro and in vivo. In conclusion, the data presented identify QSOX1 as a novel candidate target for sorafenib-based combination therapeutic strategies in HCC or other EGFR-dependent tumor types.
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http://dx.doi.org/10.1016/j.redox.2021.101942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024711PMC
May 2021

Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter.

Cell Discov 2021 Mar 23;7(1):16. Epub 2021 Mar 23.

Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.

LAT1 (SLC7A5) is one of the representative light chain proteins of heteromeric amino acid transporters, forming a heterodimer with its heavy chain partner 4F2hc (SLC3A2). LAT1 is overexpressed in many types of tumors and mediates the transfer of drugs and hormones across the blood-brain barrier. Thus, LAT1 is considered as a drug target for cancer treatment and may be exploited for drug delivery into the brain. Here, we synthesized three potent inhibitors of human LAT1, which inhibit transport of leucine with IC values between 100 and 250 nM, and solved the cryo-EM structures of the corresponding LAT1-4F2hc complexes with these inhibitors bound at resolution of up to 2.7 or 2.8 Å. The protein assumes an outward-facing occluded conformation, with the inhibitors bound in the classical substrate binding pocket, but with their tails wedged between the substrate binding site and TM10 of LAT1. We also solved the complex structure of LAT1-4F2hc with 3,5-diiodo-L-tyrosine (Diiodo-Tyr) at 3.4 Å overall resolution, which revealed a different inhibition mechanism and might represent an intermediate conformation between the outward-facing occluded state mentioned above and the outward-open state. To our knowledge, this is the first time that the outward-facing conformation is revealed for the HAT family. Our results unveil more important insights into the working mechanisms of HATs and provide a structural basis for future drug design.
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http://dx.doi.org/10.1038/s41421-021-00247-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988154PMC
March 2021

Prognostic significance of family in multiple myeloma.

J Cancer 2021 30;12(7):1936-1944. Epub 2021 Jan 30.

Department of Hematology, The Second Affiliated Hospital, Guangzhou Medical University, 510260 Guangzhou, China.

Multiple myeloma (MM) is a hematologic tumor with monoclonal proliferation of malignant plasma cells in the bone marrow. Fascin (FSCN) is an actin-binding protein that plays a crucial role in cell migration and invasion, contributing to tumor metastasis. There are three members () in family However, the prognostic role of family in MM remains unclear. In this study, we used four independent Gene Expression Omnibus (GEO) datasets to explore the relationships between expression profiles and patient survival in MM. We found that was dramatically down-regulated in MM compared to normal donors ( < 0.001) and monoclonal gammopathy of undetermined significance (MGUS) ( = 0.032). Patients with high expression of and had significantly longer OS ( = 0.023 and 0.028, respectively). Univariate and multivariate analysis showed that ( = 0.003, 0.002) and ( = 0.018, 0.013) were independent favorable prognostic factors for OS in MM. Moreover, the combination of high expression of and could effectively predict both longer EFS ( = 0.046) and OS ( = 0.015). Our study suggested that and can be used as favorable biomarkers for predicting clinical outcomes in MM.
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http://dx.doi.org/10.7150/jca.53675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974516PMC
January 2021

Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2.

Cell Res 2021 06 18;31(6):717-719. Epub 2021 Mar 18.

Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.

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http://dx.doi.org/10.1038/s41422-021-00490-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972335PMC
June 2021

Emergence and characterization of a putative novel human adenovirus recombinant HAdV-C104 causing pneumonia in Southern China.

Virus Evol 2021 Jan 2;7(1):veab018. Epub 2021 Mar 2.

State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, P. R. China.

In 2017, a survey of the molecular epidemiology of human adenovirus (HAdV) infections in Southern China based on hexon and fiber genotype demonstrated that the most prevalent genotypes of HAdV were HAdV-3 ( = 62), HAdV-2 ( = 21), and HAdV-7 ( = 16). In addition, two patients were co-infected with two genotypes of HAdV. Interestingly, a novel human adenovirus C recombinant genotype strain was isolated from one of the pneumonia patients in this survey. Phylogenetic, recombination, and proteotyping analysis showed that this novel pathogen originated from the recombination of parental viruses harboring the HAdV-1 penton and hexon gene, and the HAdV-2 fiber gene. It was named 'P1H1F2' and was assigned as HAdV-C104 based on the nomenclature protocol of using three major capsid proteins for characterization. Subsequent experiments demonstrated that HAdV-C104 had comparable proliferation capacity to HAdV-1, HAdV-2, and another recombination genotype P1H2F2. In addition, the HAdV-C104 infected patient was diagnosed with pneumonia and recovered after antiviral therapy. This report strengthens the hypothesis of recombination as a major pathway for the molecular evolution of HAdV-C species.
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http://dx.doi.org/10.1093/ve/veab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953211PMC
January 2021

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.

Cell Res 2021 05 17;31(5):517-525. Epub 2021 Mar 17.

Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, Zhejiang, 310024, China.

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.
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http://dx.doi.org/10.1038/s41422-021-00487-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966918PMC
May 2021

Cooling and diffusion characteristics of a hot carrier in the monolayer WS.

Opt Express 2021 Mar;29(5):7736-7745

The characteristics of a hot carrier distributed in the C excitonic state of the monolayer WS is investigated by exploiting the transient absorption (TA) spectroscopy. The hot carrier cooling lifetime gradually prolongs from 0.58 ps to 2.68 ps with the absorbed photon flux owing to the hot phonon bottleneck effect, as the excitation photon energy is 2.03 eV. Meanwhile, the normalized TA spectra shows that the spectral feature of hot carriers is different from that of normal carriers. Based on the modified Lennard-Jones model, the average distance among hot carriers can be estimated according to the peak shift of TA spectra and the diffusion velocity can also be calculated simultaneously. The hot carrier limits the diffusion of the photo-generated carrier at the initial several picoseconds. These results help people to elucidate the hot carrier dynamics in 2D TMDCs and give guidance on the designing and optimizing the TMDC-based electronic devices of high performance.
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http://dx.doi.org/10.1364/OE.419345DOI Listing
March 2021

Novel sodium bicarbonate activation of cassava ethanol sludge derived biochar for removing tetracycline from aqueous solution: Performance assessment and mechanism insight.

Bioresour Technol 2021 Jun 11;330:124949. Epub 2021 Mar 11.

School of Civil Engineering and Architecture, Anhui University of Technology, Ma'anshan 243032, China; Engineering Research Center of Biofilm Water Purification and Utilization Technology of Ministry of Education, Anhui University of Technology, Ma'anshan 243032, China.

NaHCO was used as a novel activator to produce cassava ethanol sludge-based biochar. The NaHCO-activated biochar showed superior adsorption capacity for tetracycline (154.45 mg/g) than raw biochar (34.04 mg/g). Orthogonal experiments confirmed the optimal preparation conditions of biochar. Increasing adsorbent dosage and temperature facilitated tetracycline removal. The maximum removal was 92.60% at pH = 3.0. Calcium ions and alkalinity decreased tetracycline removal. The time for attaining equilibrium was extended with increasing tetracycline concentration, but the equilibrium could be completed within 24 h. Langmuir model fitted the equilibrium data well. Kinetics process followed the Elovich model. The adsorption rate was controlled by both intraparticle and liquid film diffusion and the process was endothermic and spontaneous. The electrostatic attraction, hydrogen bonding, π-π interactions, and pore-filling were involved in the adsorption mechanism. The findings may provide an underlying guide for sludge disposal and removal of tetracycline from wastewater in practical application.
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http://dx.doi.org/10.1016/j.biortech.2021.124949DOI Listing
June 2021

A Flavin-Dependent Monooxygenase Mediates Divergent Oxidation of Rifamycin.

Org Lett 2021 03 8;23(6):2342-2346. Epub 2021 Mar 8.

The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Rifamycins have been clinically utilized against mycobacterial infections for more than 50 years; however, their biosynthesis has not been fully elucidated. Here, on the basis of gene deletions, enzyme assays, isotope labeling, and site-directed mutations, we found that a flavin-dependent monooxygenase encoded by a rifamycin biosynthetic gene cluster, Rif-Orf17, not only converted the naphthoquinone chromophore of rifamycin S into benzo-γ-pyrone but also linearized rifamycin SV through phenolic hydroxylation. Both oxidation routes lead to inactivation of rifamycins.
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http://dx.doi.org/10.1021/acs.orglett.1c00485DOI Listing
March 2021