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2.
Cell Prolif ; : e12989, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609051

RESUMO

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

3.
Biosens Bioelectron ; 179: 113057, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33578111

RESUMO

The rapid and early detection of foodborne pathogens in contaminated food is important for ensuring food safety and quality. In this study, a highly sensitive fluorescent immunosensor was developed to detect Escherichia coli O157:H7 in milk, by using microspheres labeled with carbon dots (CDs). The CDs-microspheres were prepared with Staphylococcus aureus cells as the carrier to incorporate CDs particles. Characterization of the microsphere revealed strong intensity, good stability and high uniformity in fluorescence. With Staphylococcal Protein A (SPA) on the surface of S. aureus cells, the microsphere could be easily coupled with various antibodies (e.g., immunoglobulin G). In combination with the immunomagnetic beads technique, a CDs-microsphere immunosensor was established for the specific detection of E. coli O157:H7 in milk. The limit of detection for E. coli O157:H7 is 2.4 × 102 colony-forming unit (CFU)/mL, comparable to that of real-time PCR methods. Milk samples spiked with E. coli O157:H7 at concentrations from 2.4 × 102 to 2.4 × 107 CFU/mL could be detected within 30 min. The coefficients of variation of the intra-assay tests were less than 10%, indicating a good repeatability. Moreover, the method was able to detect trace amounts of E. coli O157:H7 (<10 CFU) in real milk samples, with a 100% (10/10) accuracy after bacterial enrichment. This CDs-microsphere immunosensor shows considerable potential as a rapid and sensitive tool to detect pathogens in milk and other foods.

4.
J Invest Surg ; : 1-6, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33541168

RESUMO

PURPOSE: Overlapping surgery or double-booking is a vital yet disputed issue in healthcare field. However, safety of the overlapping surgery during laparoscopic common bile duct exploration (LCBDE) remains unclear. This study aimed to assess the clinical outcomes and safety of overlapping surgery during laparoscopic cholecystectomy and LCBDE for gallbladder and common bile duct stones (CBDS). MATERIAL AND METHODS: This study retrospectively reviewed 2736 laparoscopic cholecystectomy and LCBDE surgeries during 2013-2020. One thousand, two hundred eighty patients underwent LCBDE through cystic duct, including 867 receiving overlapping procedures, while 1456 underwent LCBDE through laparoscopic choledochotomy (LC), including 981 who underwent overlapping procedures. Data regarding patient sex, age, body mass index, the American Society of Anesthesiology grade, comorbidities, preoperative liver function test, previous upper abdominal surgery, presence of acute cholecystitis, cholangitis, pancreatitis, or jaundice, common bile duct (CBD) or CBDS diameter, CBDS number, LCBDE operation time, procedure duration, length of stay, stone clearance, CBD closure methods, conversion to open surgery, and complications were collected. RESULTS: Differences in demographics and clinical variables between both groups were not significant, and the unadjusted outcomes were comparable, except for the total procedure duration (transcystic: p < .001; LC: p < .001). After adjusting for demographics and clinical variables, overlapping surgery showed an extended total surgical procedure duration (transcystic: standardized coefficient = 0.084, p = .004; LC: standardized coefficient = 0.072, p = .015). Other effects of overlapping surgery were also comparable. CONCLUSIONS: Overlapping surgery in laparoscopic cholecystectomy and LCBDE was safe at our institution. However, the association of patient outcomes with overlapping laparoscopic cholecystectomy and LCBDE should be further investigated.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33543326

RESUMO

PURPOSE: Multiple myeloma (MM) remains incurable and its diagnosis relies heavily on bone marrow aspiration and biopsy. CD38 is a glycoprotein highly specific for MM. Antibody therapeutics (e.g., daratumumab) targeting CD38 have shown encouraging efficacy in treating MM, either as a monotherapy agent or in combination with other regimens. However, efficient stratification of patients who might benefit from daratumumab therapy and timely monitoring of the therapeutic responses are still clinical challenges. This work aims to devise a CD38-targeted imaging strategy and assess its value in diagnosing MMs. METHODS: By labeling a CD38-specific single domain antibody (Nb1053) with 68Ga (t1/2 = 1.1 h), we developed a CD38-targeted immuno-positron emission tomography (immunoPET) imaging probe [68Ga]Ga-NOTA-Nb1053. The probe was developed with good radiochemical yield (> 50%), excellent radiochemical purity (> 99%), and immunoreactivity (> 95%). The diagnostic accuracy of the probe was thoroughly investigated in preclinical MM models. RESULTS: ImmunoPET imaging with [68Ga]Ga-NOTA-Nb1053 specifically depicted all the subcutaneous and orthotopic MM lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. More importantly, daratumumab preloading significantly reduced [68Ga]Ga-NOTA-Nb1053 uptake in the disseminated bone lesions, indicating the overlapping targeting epitopes of [68Ga]Ga-NOTA-Nb1053 with that of daratumumab. Furthermore, premedication with sodium maleate or fructose significantly decreased kidney retention of [68Ga]Ga-NOTA-Nb1053 and improved the diagnostic value of the probe in lymphoma models. CONCLUSION: This work successfully developed a novel CD38-targeted immunoPET imaging approach that enabled precise visualization of CD38 and diagnosis of MMs. Upon clinical translation, [68Ga]Ga-NOTA-Nb1053 immunoPET may serve as a valuable CD38-targeted molecular imaging toolbox, facilitating early diagnosis of MM and precise assessment of the therapeutic responses.

6.
Genet Med ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531668

RESUMO

PURPOSE: Ciliopathies are a group of disorders caused by defects of the cilia. Joubert syndrome (JBTS) is a recessive and pleiotropic ciliopathy that causes cerebellar vermis hypoplasia and psychomotor delay. Although the intraflagellar transport (IFT) complex serves as a key module to maintain the ciliary structure and regulate ciliary signaling, the function of IFT in JBTS remains largely unknown. We aimed to explore the impact of IFT dysfunction in JBTS. METHODS: Exome sequencing was performed to screen for pathogenic variants in IFT genes in a JBTS cohort. Animal model and patient-derived fibroblasts were used to evaluate the pathogenic effects of the variants. RESULTS: We identified IFT74 as a JBTS-associated gene in three unrelated families. All the affected individuals carried truncated variants and shared one missense variant (p.Q179E) found only in East Asians. The expression of the human p.Q179E-IFT74 variant displayed compromised rescue effects in zebrafish ift74 morphants. Attenuated ciliogenesis; altered distribution of IFT proteins and ciliary membrane proteins, including ARL13B, INPP5E, and GPR161; and disrupted hedgehog signaling were observed in patient fibroblasts with IFT74 variants. CONCLUSION: IFT74 is identified as a JBTS-related gene. Cellular and biochemical mechanisms are also provided.

7.
Nucleic Acids Res ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589924

RESUMO

The ubiquitous RNA-binding protein HuR (ELAVL1) promotes telomerase activity by associating with the telomerase noncoding RNA TERC. However, the role of the neural-specific members HuB, HuC, and HuD (ELAVL2-4) in telomerase activity is unknown. Here, we report that HuB and HuD, but not HuC, repress telomerase activity in human neuroblastoma cells. By associating with AU-rich sequences in TERC, HuB and HuD repressed the assembly of the TERT-TERC core complex. Furthermore, HuB and HuD competed with HuR for binding to TERC and antagonized the function of HuR that was previously shown to enhance telomerase activity to promote cell growth. Our findings reveal a novel mechanism controlling telomerase activity in human neuroblastoma cells that involves a competition between HuR and the related, neural-specific proteins HuB and HuD.

8.
Proteins ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594723

RESUMO

Accurate prediction of peptide binding affinity to the major histocompatibility complex (MHC) proteins has the potential to design better therapeutic vaccines. Previous work has shown that pan-specific prediction algorithms can achieve better prediction performance than other approaches. However, most of the top algorithms are neural networks based black box models. Here, we propose DeepAttentionPan, an improved pan-specific model, based on convolutional neural networks and attention mechanisms for more flexible, stable and interpretable MHC-I binding prediction. With the attention mechanism, our ensemble model consisting of 20 trained networks achieves high and more stabilized prediction performance. Extensive tests on IEDB's weekly benchmark dataset show that our method achieves state-of-the-art prediction performance on 21 test allele datasets. Analysis of the peptide positional attention weights learned by our model demonstrates its capability to capture critical binding positions of the peptides, which leads to mechanistic understanding of MHC-peptide binding with high alignment with experimentally verified results. Furthermore, we show that with transfer learning, our pan model can be fine-tuned for alleles with few samples to achieve additional performance improvement. DeepAttentionPan is freely available as an open-source software at https://github.com/jjin49/DeepAttentionPan. This article is protected by copyright. All rights reserved.

9.
Surgery ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33558067

RESUMO

BACKGROUND: Whether laparoscopic gastrectomy is suitable for patients with serosa-invasive gastric cancer remains controversial. We performed this study to evaluate the short- and long-term outcomes after laparoscopic gastrectomy compared with after open gastrectomy. METHODS: We retrospectively analyzed 906 consecutive patients with serosa-invasive gastric cancer from January 2004 to December 2014 in our center, who underwent laparoscopic gastrectomy or open gastrectomy with D2 lymphadenectomy. After propensity score matching, 334 patients were included in each group. Surgical conditions and short- and long-term results were compared. RESULTS: Laparoscopic gastrectomy was associated with less estimated blood loss and longer operation time, while the number of harvested lymph nodes was not significantly different between laparoscopic gastrectomy and open gastrectomy. Patients who underwent laparoscopic gastrectomy had an earlier time to first flatus, first diet, and first ambulation and were discharged earlier. Overall and pulmonary postoperative complication rates were lower in the laparoscopic gastrectomy group. With a minimum follow-up of 60 months, the 5-year overall survival was 39.3% in the laparoscopic gastrectomy group and 34.3% in the open gastrectomy group, and the 5-year disease-free survival was 36.4% in the laparoscopic gastrectomy group and 32.7% in the open gastrectomy group. Laparoscopic gastrectomy was associated with better 5-year overall survival in patients aged ≥60 years. The overall recurrence rates and patterns were not significantly different between the 2 groups. CONCLUSION: Laparoscopic gastrectomy is an alternative surgical approach for patients with serosa-invasive gastric cancer in terms of short-term outcomes and long-term survival, and it might be more advantageous for certain populations.

10.
J Biosci Bioeng ; 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33526306

RESUMO

Increasing ethanol demand and public concerns about environmental protection promote the production of lignocellulosic bioethanol. Compared to that of starch- and sugar-based bioethanol production, the production of lignocellulosic bioethanol is water-intensive. A large amount of water is consumed during pretreatment, detoxification, saccharification, and fermentation. Water is a limited resource, and very high water consumption limits the industrial production of lignocellulosic bioethanol and decreases its environmental feasibility. In this review, we focused on the potential for reducing water consumption during the production of lignocellulosic bioethanol by performing pretreatment and fermentation at high solid loading, omitting water washing after pretreatment, and recycling wastewater by integrating bioethanol production and anaerobic digestion. In addition, the feasibility of these approaches and their research progress were discussed. This comprehensive review is expected to draw attention to water competition between bioethanol production and human use.

11.
Chem Commun (Camb) ; 57(12): 1514-1517, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33443272

RESUMO

Single-atom catalysts (SACs) have attracted much interest for electrochemical CO2 reduction because of their high metal utilization and excellent catalytic activity. However, the practical applications of SACs were restricted by the low production yield. Herein, we developed a facile synthetic strategy for fabricating metal-nitrogen-carbon nanotube (M-N-CNT, M = Ni, Co, Cu, Fe, Mn, Zn, Pt, or Ru) SACs at scale (>1 g) by direct pyrolysis of metal cations, phenanthroline and CNTs at high temperature. The pyrolysis leads to forming coordinated Ni-N active sites anchored on CNTs. The prepared Ni-N-CNT catalyst with a remarkable Ni loading of 2 wt% determined by ICP exhibits the highest activity for CO2-to-CO conversion with a high faradaic efficiency of 94% and excellent stability. Aberration-corrected high-angle annular dark-field transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy confirm the presence of isolated Ni single atoms in Ni-N-CNT, which act as the active centers for CO2 electroreduction while the CNT support offers fast pathways for electron and mass transports. This work laid foundations for future practical applications in CO2 electroreduction, oxygen reduction reactions, water splitting and nitrogen reduction and beyond.

12.
Sci Rep ; 11(1): 696, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436856

RESUMO

The surgical treatment and transcatheter arterial chemoembolization (TACE) rate of human immunodeficiency virus (HIV)-infected hepatocellular carcinoma (HCC) patients is relatively low in West China. For various reasons, most patients do not receive timely surgical treatment. Upon transfer to an infectious disease centralized hospital, they were already classified in the Barcelona Clinic Liver Cancer (BCLC)-B stage. A total of 2249 BCLC-B HCC patients were analyzed. The eligible population was divided into three groups for analysis of survival and prognostic factors; These were 21 HIV infected (HIV+) HCC patients treated with TACE (TACE+), 1293 non-HIV-infected (HIV-) HCC patients treated with TACE, and 150 HIV- HCC patients who only receive medication (TACE-) as a second control group. After 1:2 matching, 1- and 2-year survival of HIV+ TACE+ and HIV- TACE+ groups was 64.3% and 76.5% (P = 0.453) and 45.5% vs. 50.0% (P = 0.790) respectively. We also compared one and two-year survival between HIV+ TACE+ and HIV- TACE-. One-year overall survival was 64.3% vs. 45.7% (P = 0.097) and 2-year survival was 45.5% vs. 7.1% (P = 0.004). Multivariate analysis showed that the most important prognostic factors for survival were serum alpha-fetoprotein (AFP) and Child-Pugh score and tumor size, while HIV status had no significant effect on prognosis statistically. CD4 levels below 200 may increase the risk of opportunistic infection after surgery, but after anti-infection and systematic supportive therapy, it has no effect on survival. HIV+ patients should have the same treatment opportunities as HIV- patients. If the patient's immune status permits, we suggest that early TACE treatment should be administered to BCLC-B HCC patients, regardless of HIV infection.

13.
Chem Commun (Camb) ; 57(12): 1434-1437, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33514953

RESUMO

A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our work provides a general strategy not only for improving the anti-cancer efficacy of protein-drug conjugates but also for increasing the efficiency of other types of endocytosis-dependent cell delivery.

14.
Int J Biol Macromol ; 172: 231-240, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453253

RESUMO

Photodynamic inactivation (PDI) is a novel sterilization technology that has proven effective in medicine. This study focused on applying PDI to food packaging, where chitosan (CS) films containing photosensitizing riboflavin (RB) were prepared via solution casting. The CS-RB composite films exhibited good ultraviolet (UV)-barrier properties, and had a visually appealing highly transparent yellow appearance. Scanning electron microscopy (SEM) confirmed even dispersion of RB throughout the CS film. The addition of RB led to improved film characteristics, including the thickness, mechanical properties, solubility, and water barrier properties. The CS-RB5 composite films produced sufficient singlet oxygen under blue LED irradiation for 2 h to inactivate two food-borne pathogens (Listeria monocytogenes and Vibrio parahaemolyticus) and one spoilage bacteria (Shewanella baltica). The CS-RB composite films were assessed as a salmon packaging material, where inhibition of bacterial growth was observed. The film is biodegradable, and has the potential to alleviate the issues associated with the excessive use of petrochemical materials, such as environmental pollution and limited resources. The CS-RB composite films showed potential as a novel environmentally friendly packaging material for shelf-life extension of refrigerated food products.

15.
Surg Endosc ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492501

RESUMO

BACKGROUND: In this study, we investigated the incidence and risk factors for postoperative complications after robotic gastrectomy (RG) in patients with gastric cancer. METHODS: A total of 817 patients who underwent RG for gastric cancer between March 2010 and August 2019 were analyzed retrospectively. Postoperative complications were categorized according to the Clavien-Dindo classification, and possible risk factors were evaluated. RESULTS: Among 817 patients who underwent RG, overall, severe, local and systemic complication rates were 13.8, 4.2, 7.0 and 6.9%, respectively. Multivariable analysis revealed that an age of 70 years or older (P < 0.001) and multiorgan resection (P = 0.031) were independent risk factors for the occurrence of overall complications. Multivariable analysis showed that an age of 70 years or older (P = 0.005) and surgeons' experience ≤ 25 cases (P = 0.004) were independent risk factors for severe complications. Regarding local complications, an age of 70 years or older (P < 0.001), multiorgan resection (P = 0.010) and surgeons' experience ≤ 25 cases (P = 0.005) were identified as independent risk factors. An age of 70 years or older (P < 0.001), a BMI of 25 or higher (P = 0.045) and the presence of comorbidity (P = 0.029) were identified as independent risk factors for systemic complications. CONCLUSIONS: The present study demonstrated that RG is a safe and feasible procedure for the treatment of gastric cancer, and it has an acceptable postoperative morbidity. Elderly patients and insufficient surgeon experience were two major risk factors for the occurrence of complications following RG. We suggest that surgeons choose patients in good condition during their RG learning phase to reduce learning-associated morbidity.

16.
Crit Rev Food Sci Nutr ; : 1-42, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459057

RESUMO

Tyrosinase is a copper-containing oxidation enzyme, which is responsible for the production of melanin. This enzyme is widely distributed in microorganisms, animals and plants, and plays an essential role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, neurodegeneration, etc. Hence, it has been recognized as a therapeutic target for the development of antibrowning agents, antibacterial agents, skin-whitening agents, insecticides, and other therapeutic agents. With great potential application in food, agricultural, cosmetic and pharmaceutical industries, a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. In this review, we systematically summarized the advances of synthetic tyrosinase inhibitors in the literatures, including their inhibitory activity, cytotoxicity, structure-activity relationship (SAR), inhibition kinetics, and interaction mechanisms with the enzyme. The collected information is expected to provide a rational guidance and effective strategy to develop novel, potent and safe tyrosinase inhibitors for better practical applications in the future.

17.
J Biotechnol ; 327: 106-116, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33421510

RESUMO

Soil salinity is one of the major environmental factors, influencing agricultural productivity of crops. As a non-edible and ideal oilseed crop, castor (Ricinus communis L.) has great industrial value in biofuel, but molecular mechanisms of salt stress regulation are still unknown. In this study, the differentially expressed genes (DEGs) for differential salt tolerance in two castor cultivar (wild castor : Y, cultivated castor 'Tongbi 5': Z) were identified. 12 libraries were sampled for Illumina high-throughput sequencing to consider 132,426 nonredundant unigenes and 31,221 gene loci. Multiple phytohormones and transcription factors (TFs) were correlated with salt-tolerance and differently enriched in these two genotypes. The type 2C protein phosphatases (PP2C) homologs were all upregulated under salt stress. Importantly, IAA (1), DELLA (1) and Jasmonate zim domain (JAZ) (1) were also identified and found to be differentially expressed. Based on the co-expressed module by regulatory networks and heatmap analysis, ERF/AP2, WRKY and bHLH families were prominently participate in high salt stress response of wild and cultivated castor. Finally, these results highlight that the hub DEGs and families were more accumulated in cultivated castor than those in wild castor, providing novel insights into the salinity adaptive mechanisms and genetic improvement in castor.

18.
J Drug Target ; : 1-7, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33472448

RESUMO

Chemokines may promote the formation and instability of atherosclerotic plaque, which is the most common cause of acute coronary syndrome. The aim of this study was to clarify the function of monocyte chemotactic protein-3 (MCP-3) in the stability of atherosclerotic plaque, to determine the role of tissue factor pathway inhibitor (TFPI) on the development and stability of atherosclerotic plaques, and to further elucidate the anti-atherosclerotic mechanism of TFPI with the emphasis on chemokine MCP-3. We constructed an adenovirus-mediated shRNA against mouse MCP-3 (Ad-MCP-3-shRNA) and an adenovirus-containing TFPI (Ad-TFPI), and tranferred them in a model of vulnerable plaque in ApoE-/- mice respectively. Here, we reported that MCP-3-shRNA and TFPI could both reduce the plaque area and decrease the content of lipids and macrophages, on the contrary, the fibrous cap thickness and content of collagen and smooth muscle cells were increased. In addition, the expression of MCP-3 and CC chemokine receptor 2 (CCR2) was decreased by TFPI transfer. These data provide the first in vivo evidence that MCP-3 is a major contributor to the unstability of atherosclerotic plaque and TFPI may exert its anti-atherosclerotic effects and promote stabilisation of plaque at least partly through inhibiting MCP-3/CCR2 pathway, which may be a new therapeutic method for atherosclerosis.

19.
Nat Commun ; 12(1): 488, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473130

RESUMO

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC50 of 2.1 µM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLproC111S in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.


Assuntos
Antivirais/química , Antivirais/farmacologia , /química , /efeitos dos fármacos , /metabolismo , /genética , Citocinas/metabolismo , Descoberta de Drogas , Interações Medicamentosas , Células HEK293 , Ensaios de Triagem em Larga Escala , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Pandemias , Conformação Proteica , /metabolismo , Ubiquitinas/metabolismo
20.
Sci Total Environ ; 765: 144276, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33401056

RESUMO

With 80% water resources in the south and 65% arable land in the north, China is facing a rigorous challenge due to the spatial mismatch between water distribution and food & energy production to make a balanced development of economy and ecosystem. In the past decades, the northwest has played a prominent role in maintaining national food and energy security. However, the lack of water resources in this region poses a great threat to sustainable development. Based on this, this study quantitatively analyzed the evolution trend of water footprint (WF) of major crops and energy products in Northwest China from 2000 to 2015 and revealed the virtual water (VW) transfer pattern with commodity trade and its water resource stress caused by the virtual water output. The results show that, although the improvement of technology has greatly reduced the WF per unit production, the northwest region is still a net VW output area, whose net VW output associated with food and energy trade is increasing sharply from 287.2 × 108 m3 (2000) to 328.5 × 108 m3 (2015) with a growth rate of 14.4%, seriously aggravating the local water resource pressure. To ensure the water, food and energy safety of the northwest, we proposed countermeasures and suggestions on technological development and strategic planning, including water-saving technology promotion, industrial and agricultural structure optimization, and the coordinated management of physical and virtual water. The above findings provide a scientific reference to ensure the sustainable development of Northwest China.

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