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1.
Food Chem ; 370: 131013, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509150

RESUMO

Malus micromalus Makino has great commercial and nutritional value. The regression and classification models were investigated by using near-infrared hyperspectral imaging (NIR-HSI) combined with chemometrics to improve the efficiency of non-destructive detection. The successive projections algorithm (SPA), interval random frog, and competitive adaptive reweighted sampling were employed to extract effective wavelengths sensitive to changes of soluble solid content (SSC) and firmness index (FI) information. Two types of assessment models based on full spectrum and effective wavelengths, namely partial least squares regression and extreme learning machine, were established to predict SSC and FI. In addition, the classification models based on the support vector machine improved by the grey wolf optimizer (GWO-SVM) and partial least squares discrimination analysis were constructed to differentiate maturity stage. The SPA-ELM and SPA-GWO-SVM models achieved satisfactory performance. The results illustrate that NIR-HSI is feasible for evaluation of the quality of Malus micromalus Makino.


Assuntos
Malus , Algoritmos , Imageamento Hiperespectral , Análise dos Mínimos Quadrados , Espectroscopia de Luz Próxima ao Infravermelho , Máquina de Vetores de Suporte
2.
Plant Cell ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34735009

RESUMO

The self-incompatibility (SI) system with the broadest taxonomic distribution in angiosperms is based on multiple S-locus F-box genes (SLFs) tightly linked to an S-RNase termed type-1. Multiple SLFs collaborate to detoxify non-self S-RNases while being unable to detoxify self S-RNases. However, it is unclear how such a system evolved, because in an ancestral system with a single SLF, many non-self S-RNases would not be detoxified, giving low cross-fertilization rates. In addition, how the system has been maintained in the face of whole-genome duplications (WGD) or lost in other lineages remains unclear. Here we show that SLFs from a broad range of species can detoxify S-RNases from Petunia with a high detoxification probability, suggestive of an ancestral feature enabling cross-fertilization and subsequently modified as additional SLFs evolved. We further show, based on its genomic signatures, that type-1 was likely maintained in many lineages, despite WGD, through deletion of duplicate S-loci. In other lineages, SI was lost either through S-locus deletions or by retaining duplications. Two deletion lineages regained SI through type-2 (Brassicaceae) or type-4 (Primulaceae) and one duplication lineage through type-3 (Papaveraceae) mechanisms. Thus, our results reveal a highly dynamic process behind the origin, maintenance, loss and regain of SI.

3.
Front Neural Circuits ; 15: 655502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776874

RESUMO

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients. Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (H max/M max ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention. Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in H max/M max ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group. Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).

4.
Medicine (Baltimore) ; 100(41): e27351, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731107

RESUMO

BACKGROUND: Guillain-Barre syndrome (GBS) is a disease with the features of acuteness, paralysis, inflammation, and in peripheral nerves. There are many current treatment options with varying efficacy, and to assess their effectiveness, we performed a network meta-analysis (NMA). The study protocol was registered at PROSPERO (CRD: 42019119178). Posted history: this manuscript was previously posted to medRxiv: doi: https://doi.org/10.1101/2020.06.03.20121780. METHODS: The literature search database includes Web of Science, PubMed, Embase, and the Cochrane library that meets the requirements. We performed the NMA using controlled trials with 2 kinds of outcomes. We used the gemtc R package to perform the NMA to evaluate different GBS treatments' relative results. The consistency of direct and indirect evidence was also assessed by R software with gemtc package. RESULTS: This NMA study included a total of 2474 subjects from 28 trials with 15 kinds of therapies. No improvement was observed in methylprednisolone and prednisolone compared with placebo. Conversely, plasma exchange (PE) and intravenous immunoglobulin (IVIg) were more effective than placebo. There was no significant difference between different doses and courses of PE and IVIg. For combination treatment, such as IVIg+eculizumab, immunoadsorption followed by IVIg and PE followed by IVIg, they didn't show significant advantages than IVIg and PE in NMA. On the consistency examination between direct and indirect evidence, there was no apparent heterogeneity between them. Funnel plots indicated there was little possibility of publication bias in this study. CONCLUSION: PE or IVIg has significant efficacy for GBS patients. The effects of several kinds of therapies should be further explored. Corticosteroids have no considerable impact on GBS.


Assuntos
Síndrome de Guillain-Barré/terapia , Avaliação de Resultados em Cuidados de Saúde , Terapia Combinada , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Metilprednisolona/uso terapêutico , Metanálise em Rede , Troca Plasmática
5.
J Hepatol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34793865

RESUMO

BACKGROUND & AIMS: To investigate the prognostic value and relevant mechanisms of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA). METHODS: We retrospectively included 962 patients from three cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples. RESULTS: A quaternary TLS scoring system was established for intra-tumor region (T score) and peri-tumor region (P score) respectively. T score positively correlated with favorable prognosis (P<0.001), whereas a high P score signified a worse survival (P<0.001). Then, mIHC demonstrated that both Tfh and Treg cells were significantly increased in intra-tumor TLSs than peri-tumor counterparts (P<0.05), and Treg cell frequencies within intra-tumor TLSs were positively associated with P score (P<0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into four Immune Classes with distinct prognosis (P<0.001) that differed in the abundance and distribution pattern of TLSs. Patients displayed an immune active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with immune excluded pattern survived at 5 years (P<0.001). The C-index of the Immune Class was statistically higher than the TNM staging system (0.73 vs 0.63, P<0.001). These results were validated in an internal and two external cohorts. CONCLUSIONS: The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. Tfh and Treg cells may play a critical role in determining the functional orientation of spatially different TLSs. LAY SUMMARY: Tertiary lymphoid structures (TLSs) have been attracting extensive attentions as they are associated with favorable prognosis through activating endogenous anti-tumor immune response. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains elusive. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed opposite prognostic impacts of TLSs located within or outside tumor region. The heterogeneous distribution of Tfh and Treg cells within the spatially different TLSs might be determinant of their functional state. Successfully, the integrated analysis of TLSs stratified iCCAs into four immune subclasses with distinct clinical outcomes.

6.
ACS Omega ; 6(45): 30627-30643, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34805691

RESUMO

The requirement of improving efficiency and performance leads to the continuous development of furnaces and burners. For this purpose, it is necessary to establish a model suitable for industrial production and adjust it according to industrial demand. In this paper, a comprehensive numerical model is developed to characterize the combustion, heat transfer, and slab heating in an indirect reheating furnace with pulse combustion. To realize the pulse combustion process, a pulse control approach based on a user-defined function (UDF) was proposed to control the radiant tube burner state. Indirect heat transfer in the furnace was realized by coupling the radiant tubes and the furnace as a whole. In a simulation with the eddy dissipation concept (EDC) model, results from the four-step mechanism were in close accordance with those of the GRI 3.0 mechanism, and both mechanisms could describe the combustion process in detail. However, the calculation time of the EDC model with the four-step mechanism was reduced significantly. Thus, the EDC model with the four-step mechanism was selected as the ideal combustion model used for further simulation research. Through experimental validation, the simulation results of the developed model using the EDC model with the four-step mechanism showed a good agreement with the experimental results. Additionally, with this model, the effects of oxygen-enriched combustion with 74 vol % N2 and 26 vol % O2 in the oxidizer and inlet-change case with a fuel inlet and a primary air inlet on the performance of an indirect reheating furnace with pulse combustion were specially studied. The maximum flame temperature and the average temperature of the furnace atmosphere increased from 2046 to 2175 K and from 1241 to 1279 K for increased oxygen concentration, respectively. Compared with air-fuel combustion, the discharging slab temperature reached a growth of 2.9% in oxygen-enriched combustion. After changing the inlet boundary of the radiant tube burners, since the excessive combustion in the burner's combustion chamber was avoided and the full combustion of fuel in the radiant tubes was promoted, the flame intensity in the radiant tubes was enhanced and the maximum flame temperature reached 2196 K. At the same time, the mole fraction of CO at the outlet became smaller and the slab temperature in all zones of the furnace increased by more than 3.5%. This study showed that higher efficiency of an indirect reheating furnace with pulse combustion can be achieved by oxygen-enriched combustion and changing the inlet boundary of the burners.

7.
Front Neurosci ; 15: 688569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764848

RESUMO

Objectives: The objective of this study was to explore the efficacy of cerebellar intermittent theta burst stimulation (iTBS) on the walking function of stroke patients. Methods: Stroke patients with walking dysfunction aged 25-80 years who had suffered their first unilateral stroke were included. A total of 36 patients [mean (SD) age, 53 (7.93) years; 10 women (28%)] were enrolled in the study. All participants received the same conventional physical therapy, including transfer, balance, and ambulation training, during admission for 50 min per day during 2 weeks (10 sessions). Every session was preceded by 3 min procedure of cerebellar iTBS applyed over the contralesional cerebellum in the intervention group or by a similar sham iTBS in control group. The groups were formed randomly and the baseline characteristics showed no significant difference. The primary outcome measure was Fugl-Meyer Assessment-Lower Extremity scores. Secondary outcomes included walking performance and corticospinal excitability. Measures were performed before the intervention beginning (T0), after the first (T1) and the second (T2) weeks. Results: The Fugl-Meyer Assessment for lower extremity scores slightly improved with time in both groups with no significant difference between the groups and over the time. The walking performance significantly improved with time and between group. Two-way mixed measures ANOVA showed that there was significant interaction between time and group in comfortable walking time (F 2,68 = 6.5242, P = 0.0080, η2 partial = 0.276, ε = 0.641), between-group comparisons revealed significant differences at T1 (P = 0.0072) and T2 (P = 0.0133). The statistical analysis of maximum walking time showed that there was significant interaction between time and groups (F 2,68 = 5.4354, P = 0.0115, η2 partial = 0.198, ε = 0.734). Compared with T0, the differences of maximum walking time between the two groups at T1 (P = 0.0227) and T2 (P = 0.0127) were statistically significant. However, both the Timed up and go test and functional ambulation category scale did not yield significant differences between groups (P > 0.05). Conclusion: Our results revealed that applying iTBS over the contralesional cerebellum paired with physical therapy could improve walking performance in patients after stroke, implying that cerebellar iTBS intervention may be a noninvasive strategy to promote walking function in these patients. This study was registered at ChiCTR, number ChiCTR1900026450.

8.
Eur J Med Chem ; : 113974, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34772528

RESUMO

GYH2-18 is a type II HBV CAM with 6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxamine (DPPC) skeleton discovered by Roche INC. A series of GYH2-18 derivatives were designed, synthesized and evaluated for their anti-HBV activity. Two compounds 2f and 3k exhibited excellent anti-HBV activity, low cytotoxicity and accepted oral PK profiles. Chiral separation of 2f and 3k was conducted successfully, and (6S)-cyclopropyl DPPC isomers 2f-1, 2f-3, 3k-1 and 3k-3 were identified to be much more active than the corresponding (6R)-ones. The preliminary structure-activity relationship, particle gel assay and molecular modeling studies were also discussed, which provide useful indications for guiding the further rational design of new (6S)-cyclopropyl DPPC analogues.

9.
Front Plant Sci ; 12: 738042, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745172

RESUMO

Real-time dynamic monitoring of orchard grape leaf diseases can greatly improve the efficiency of disease control and is of great significance to the healthy and stable development of the grape industry. Traditional manual disease-monitoring methods are inefficient, labor-intensive, and ineffective. Therefore, an efficient method is urgently needed for real-time dynamic monitoring of orchard grape diseases. The classical deep learning network can achieve high accuracy in recognizing grape leaf diseases; however, the large amount of model parameters requires huge computing resources, and it is difficult to deploy to actual application scenarios. To solve the above problems, a cross-channel interactive attention mechanism-based lightweight model (ECA-SNet) is proposed. First, based on 6,867 collected images of five common leaf diseases of measles, black rot, downy mildew, leaf blight, powdery mildew, and healthy leaves, image augmentation techniques are used to construct the training, validation, and test set. Then, with ShuffleNet-v2 as the backbone, an efficient channel attention strategy is introduced to strengthen the ability of the model for extracting fine-grained lesion features. Ultimately, the efficient lightweight model ECA-SNet is obtained by further simplifying the network layer structure. The model parameters amount of ECA-SNet 0.5× is only 24.6% of ShuffleNet-v2 1.0×, but the recognition accuracy is increased by 3.66 percentage points to 98.86%, and FLOPs are only 37.4 M, which means the performance is significantly better than other commonly used lightweight methods. Although the similarity of fine-grained features of different diseases image is relatively high, the average F1-score of the proposed lightweight model can still reach 0.988, which means the model has strong stability and anti-interference ability. The results show that the lightweight attention mechanism model proposed in this paper can efficiently use image fine-grained information to diagnose orchard grape leaf diseases at a low computing cost.

10.
Sensors (Basel) ; 21(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34640890

RESUMO

In recent years, machine learning for trading has been widely studied. The direction and size of position should be determined in trading decisions based on market conditions. However, there is no research so far that considers variable position sizes in models developed for trading purposes. In this paper, we propose a deep reinforcement learning model named LSTM-DDPG to make trading decisions with variable positions. Specifically, we consider the trading process as a Partially Observable Markov Decision Process, in which the long short-term memory (LSTM) network is used to extract market state features and the deep deterministic policy gradient (DDPG) framework is used to make trading decisions concerning the direction and variable size of position. We test the LSTM-DDPG model on IF300 (index futures of China stock market) data and the results show that LSTM-DDPG with variable positions performs better in terms of return and risk than models with fixed or few-level positions. In addition, the investment potential of the model can be better tapped by the reward function of the differential Sharpe ratio than that of profit reward function.


Assuntos
Investimentos em Saúde , Memória de Longo Prazo , Previsões , Aprendizado de Máquina , Políticas
11.
Artigo em Inglês | MEDLINE | ID: mdl-34699010

RESUMO

Fully utilizing the energy generated by the explosion of pulverized coal will contribute to realize the clean and efficient exploitation of coal resources. The pulverized coal explosion characteristics will be a far-reaching and important task to explore. In this paper, ten kinds of low-quality coals such as high sulfur, high ash, and low metamorphic degree coals were investigated and the minimum ignition energy (MIE), lower explosion limit (LEL), and explosion intensity (EI) parameters under different particle sizes and coal powder concentration conditions were also analyzed combined with a 1.2-L Hartmann tube and a 20-L explosion sphere experimental system. Finally, the morphological characteristics of the exploded coal powder surface were evaluated by scanning electron microscopy (SEM). The results show that the particle size is positively correlated with MIE. LEL shows an inverted "U"-shaped trend with the increasing degree of coal deterioration. The low-rank coal is more flammable and explosive. The maximum pressure PMax at the LEL concentration and maximum pressure rise rate (dP/dt)Max overall value is small. Here, optimum pulverized coal particle size (75µm) for explosive utilization of low-quality coal was determined. Within 50-225 g/m3 of pulverized coal concentration range, the explosion intensity increases with increasing concentration. The smaller the particle size of pulverized coal, the greater the possibility of agglomeration of pulverized coal particles. The surface of the exploded coal particles produces more developed pores. They are irregularly shaped and have more rounded edges than the original coal.

12.
Crit Rev Biotechnol ; : 1-20, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34634988

RESUMO

Abnormal vasoconstriction, inflammation, and vascular remodeling can be promoted by angiotensin II (Ang II) in the renin-angiotensin system (RAS), leading to vascular dysfunction diseases such as hypertension and atherosclerosis. Researchers have recently focused on angiotensin I-converting enzyme inhibitory peptides (ACEIPs), that have desirable efficacy in vascular dysfunction therapy due to Ang II reduction by inhibiting ACE activity. Promising methods for the large-scale preparation of ACEIPs include selective enzymatic hydrolysis and microbial fermentation. Thus far, ACEIPs have been widely reported to be hydrolyzed from protein-rich sources, including animals, plants, and marine organisms, while many emerging microorganism-derived ACEIPs are theoretically biosynthesized through the nonribosomal peptide synthase (NRPS) pathway. Notably, vasodilatation, anti-inflammation, and vascular reconstruction reversal of ACEIPs are strongly correlated. However, the related molecular mechanisms underlying signal transduction regulation in vivo remain unclear. We provide a comprehensive update of the ACE-Ang II-G protein-coupled type 1 angiotensin receptor (AT1R) axis signaling and its functional significance for potential translation into therapeutic strategies, particularly targeting AT1R by ACEIPs, as well as specific related signaling pathways. Future studies are expected to verify the biosynthetic regulatory mechanism of ACEIPs via the NRPS pathway, the effect of gut microbiota metabolism on vascular dysfunction and rigorous studies of ACE-Ang II-AT1R signaling pathways mediated by ACEIPs in large animals and humans.

13.
ACS Appl Mater Interfaces ; 13(42): 50461-50469, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34641666

RESUMO

Developing surfaces that realize lubrication and durable wear resistance under high pressure has great implications in areas ranging from electromechanical systems to advanced biomedical devices but has proven challenging. Inspired by the zonal and transitional structure of articular cartilage, we fabricate a hydrogel-elastomer hybrid surface, where the hydrogel interpenetrates into the polymer elastomer substrate as a transitional and bonding zone, that exhibits a low coefficient of friction and wear resistance under a high load. First, we entrap benzophenone within the surface of polymer substrates such as polydimethylsiloxane, polyvinylchloride, and polyurethane. The hybrid surface is then achieved through initiating polymerization of the acrylamide monomer on the polymer surface upon ultraviolet irradiation. We observe an interpenetration area of the hydrogel and the polymer substrate. The hybrid surface shows a low coefficient of friction (∼0.05) under a very high load (over 100 atm contact pressure). It conserves the lubrication property over 100,000 cycles under a 10.9 MPa pressure and shows slight wear. This work brings a new perspective on designing surfaces with a lubrication property and wear resistance, showing broad applications.

14.
Vaccine ; 39(44): 6520-6528, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34620531

RESUMO

BACKGROUND: The WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose. RESULTS: Most of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%. CONCLUSIONS: From the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Indonésia/epidemiologia , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos
15.
J Tradit Chin Med ; 41(5): 771-778, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34708636

RESUMO

OBJECTIVE: To explore the neuroprotective mechanisms of Tongluo Huatan capsule (THC) in a rat model of vascular dementia (VD). METHODS: A rat model of VD was established by repeated clamping of bilateral common carotid arteries with the intraperitoneal injection of sodium nitroprusside solution. VD rats were administered THC, memantine hydrochloride, or distilled water daily for 14 d after operation. Learning and memory abilities were assessed using the step-down passive avoidance test, novel object recognition (NOR) test, and Morris water maze (MWM) test. Pathological changes in the hippocampus were observed through hematoxylin and eosin and Nissl staining. The expression levels of clathrin, RAB5B, and N-methyl-D-aspartic acid receptor 1 (NMDAR1) were measured by immunohistochemistry staining, real-time quantitative polymerase chain reaction and Western blot. RESULTS: Rats in VD group showed impaired learning and memory abilities (step-down passive avoidance, NOR, and MWM) and abnormalities in neuronal morphology (light microscopy) in the hippocampus. The mRNA or protein expression levels of clathrin and RAB5B were decreased, and NMDAR1 was increased in hippocampal tissues (P < 0.05). Administration of THC promoted the learning and memory abilities and the morphological structure of hippocampal neurons in VD rats. Besides, THC enhanced mRNA or protein expression levels of clathrin and RAB5B, and decreased NMDAR1 (P < 0.05). CONCLUSION: THC may improve cognitive functions by regulating the endocytosis of NMDA receptors mediated by clathrin.

16.
Elife ; 102021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633289

RESUMO

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells' cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100 % specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.

17.
Biotechnol Adv ; 53: 107841, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610353

RESUMO

Metabolic energy (ME) homeostasis is essential for the survival and proper functioning of microbial cell factories. However, it is often disrupted during bioproduction because of inefficient ME supply and excessive ME consumption. In this review, we propose strategies, including reinforcement of the capacity of ME-harvesting systems in autotrophic microorganisms; enhancement of the efficiency of ME-supplying pathways in heterotrophic microorganisms; and reduction of unessential ME consumption by microbial cells, to address these issues. This review highlights the potential of biotechnology in the engineering of microbial ME homeostasis and provides guidance for the higher efficient bioproduction of microbial cell factories.

18.
Genome Med ; 13(1): 166, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663432

RESUMO

BACKGROUND: Liver cancer is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related death worldwide. Broad-spectrum kinase inhibitors like sorafenib and lenvatinib provide only modest survival benefit to patients with hepatocellular carcinoma (HCC). This study aims to identify novel therapeutic strategies for HCC patients. METHODS: Integrated bioinformatics analyses and a non-biased CRISPR loss of function genetic screen were performed to identify potential therapeutic targets for HCC cells. Whole-transcriptome sequencing (RNA-Seq) and time-lapse live imaging were performed to explore the mechanisms of the synergy between CDC7 inhibition and ATR or CHK1 inhibitors in HCC cells. Multiple in vitro and in vivo assays were used to validate the synergistic effects. RESULTS: Through integrated bioinformatics analyses using the Cancer Dependency Map and the TCGA database, we identified ATR-CHK1 signaling as a therapeutic target for liver cancer. Pharmacological inhibition of ATR or CHK1 leads to robust proliferation inhibition in liver cancer cells having a high basal level of replication stress. For liver cancer cells that are resistant to ATR or CHK1 inhibition, treatment with CDC7 inhibitors induces strong DNA replication stress and consequently such drugs show striking synergy with ATR or CHK1 inhibitors. The synergy between ATR-CHK1 inhibition and CDC7 inhibition probably derives from abnormalities in mitosis inducing mitotic catastrophe. CONCLUSIONS: Our data highlights the potential of targeting ATR-CHK1 signaling, either alone or in combination with CDC7 inhibition, for the treatment of liver cancer.

19.
Proc Natl Acad Sci U S A ; 118(36)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34470821

RESUMO

Mechanical forces generated by cells and the tension of the extracellular matrix (ECM) play a decisive role in establishment, homeostasis maintenance, and repair of tissue morphology. However, the dynamic change of cell-derived force during large-scale remodeling of soft tissue is still unknown, mainly because the current techniques of force detection usually produce a nonnegligible and interfering feedback force on the cells during measurement. Here, we developed a method to fabricate highly stretchable polymer-based microstrings on which a microtissue of fibroblasts in collagen was cultured and allowed to contract to mimic the densification of soft tissue. Taking advantage of the low-spring constant and large deflection range of the microstrings, we detected a strain-induced contraction force as low as 5.2 µN without disturbing the irreversible densification. Meanwhile, the microtissues displayed extreme sensitivity to the mechanical boundary within a narrow range of tensile stress. More importantly, results indicated that the cell-derived force did not solely increase with increased ECM stiffness as previous studies suggested. Indeed, the cell-derived force and collagen tension exchanged dramatically in dominating the microtissue strain during the densification, and the proportion of cell-derived force decreased linearly as the microtissue densified, with stiffness increasing to ∼500 Pa. Thus, this study provides insights into the biomechanical cross-talk between the cells and ECM of extremely soft tissue during large-extent densification, which may be important to guide the construction of life-like tissue by applying appropriate mechanical boundary conditions.

20.
Biotechnol Biofuels ; 14(1): 189, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563244

RESUMO

BACKGROUND: Lignin is a complex aromatic heteropolymer comprising 15-30% dry weight of the lignocellulose. The complex structural characteristic of lignin renders it difficult for value-added utilization. Exploring efficient lignin-degrading microorganisms and investigating their lignin-degradation mechanisms would be beneficial for promoting lignin valorization. In this study, a newly isolated white-rot basidiomycete, Trametes hirsuta X-13, with capacity to utilize alkaline lignin as the sole substrate was investigated. RESULTS: The analysis of the fermentation properties of T. hirsuta X-13 using alkaline lignin as the sole substrate, including the mycelial growth, activities of ligninolytic enzymes and the rates of lignin degradation and decolorization confirmed its great ligninolysis capacity. The maximum lignin degradation rate reached 39.8% after 11 days of T. hirsuta X-13 treatment, which was higher than that of reported fungi under the same condition. Fourier transform infrared spectrometry (FTIR), gas chromatography-mass spectrometry (GC-MS) scanning electron micrographs (SEM), two-dimensional heteronuclear single quantum coherence NMR analysis (2D-HSQC NMR) collaborated with pyrolysis gas chromatography-mass spectrometry (py-GC/MS) analyses proved that lignin structure was severely deconstructed along with amounts of monomer aromatics generated. Furthermore, according to those chemical analysis, in addition to canonical Cα-Cß breakage, the cleavage of lignin interunit linkages of ß-ß might also occur by T. hirsuta X-13. CONCLUSIONS: This study characterized a newly isolated white-rot basidiomycete T. hirsuta X-13 with impressive alkaline lignin degradation ability and provided mechanistic insight into its ligninolysis mechanism, which will be valuable for the development of lignin valorization strategies.

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