Publications by authors named "Yi Liu"

5,675 Publications

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Rapid detection of the irinotecan-related UGT1A1*28 polymorphism by asymmetric PCR melting curve analysis using one fluorescent probe.

J Clin Lab Anal 2022 Jun 29:e24578. Epub 2022 Jun 29.

Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.

Background: Determination of UGT1A1 (TA) polymorphism prior to irinotecan therapy is necessary to avoid severe adverse drug effects. Thus, accurate and reliable genotyping methods for (TA) polymorphism are highly desired. Here, we present a new method for polymerase chain reaction (PCR) melting curve analysis using one fluorescent probe to discriminate the UGT1A1*1 [(TA) ] and *28 [(TA) ] genotypes.

Methods: After protocol optimization, this technique was applied for genotyping of 64 patients (including 23 with UGT1A1*1/*1, 22 with *1/*28, and 19 with *28/*28) recruited between 2016 and 2021 in China-Japan Friendship Hospital. The accuracy of the method was evaluated by comparing the results with those of direct sequencing and fragment analysis. The intra- and inter-run precision of the melting temperatures (T s) were calculated to assess the reliability, and the limit of detection was examined to assess the sensitivity.

Results: All genotypes were correctly identified with the new method, and its accuracy was higher than that of fragment analysis. The intra- and inter-run coefficients of variation for the T s were both ≤0.27%, with standard deviations ≤0.14°C. The limit of detection was 0.2 ng of input genomic DNA.

Conclusion: The developed PCR melting curve analysis using one fluorescent probe can provide accurate, reliable, rapid, simple, and low-cost detection of UGT1A1 (TA) polymorphism, and its use can be easily generalized in clinical laboratories with a fluorescent PCR platform.
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http://dx.doi.org/10.1002/jcla.24578DOI Listing
June 2022

Novel splice variants, expression and their association with growth traits in goose.

Br Poult Sci 2022 Jun 29. Epub 2022 Jun 29.

Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, P.R. China.

1. The gene has been reported as being related to the body size and body weight in ducks, goats and chickens. However, this potential growth-related gene has not yet been reported in geese.2. The goose cDNA (IGF2BP1-X1) is 2,925 bp in length, containing an open reading frame (ORF) of 1,731 bp that encodes a protein of 576 amino acids. Six transcripts (IGF2BP1-X2∼IGF2BP1-X7) were identified due to the alternative splicing of different exons within the IGF2BP1-X1 transcript.3. RT-qPCR analysis indicated that the goose mRNA was differentially expressed in the examined tissues of the female embryos (28 d of development), adult (70 d of age) and laying (270 d of age) of Zhedong White geese.4. In total, 16 single nucleotide polymorphisms (SNPs) and three insertion/deletion (InDel) variants were detected in several introns and 3'-untranslated regions of the goose gene. The 17-bp InDel within intron 14 was significantly associated with body weight at six weeks old (BW6, P<0.05), and extremely significantly associated with the BW8 and BW10 (P<0.01) of geese.
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http://dx.doi.org/10.1080/00071668.2022.2094220DOI Listing
June 2022

Safety evaluation of the food enzyme rennet containing chymosin and pepsin A from calf abomasum.

EFSA J 2022 Jun 20;20(6):e07361. Epub 2022 Jun 20.

The food enzyme containing chymosin (EC 3.4.23.4) and pepsin A (EC 3.4.23.1) is prepared from the abomasum of calves by RENCO New Zealand. The food enzyme is intended to be used in milk processing for cheese production. As no concerns arise from the animal source of the food enzyme or from its manufacture and based on the history of safe use and consumption, the Panel considered that toxicological data were not required, and the estimation of dietary exposure was unnecessary. On the basis of literature data, the Panel considered that the risk of allergic sensitisation and elicitation reactions by dietary exposure could not be excluded, but the likelihood for this to occur was considered to be low. The Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2022.7361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208323PMC
June 2022

Clinical characteristics and vaccine effectiveness against SARS-CoV-2 Omicron subvariant BA.2 in the children.

Signal Transduct Target Ther 2022 Jun 28;7(1):203. Epub 2022 Jun 28.

Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, No. 29, Bulan Road, Longgang District, Shenzhen, 518112, P. R. China.

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http://dx.doi.org/10.1038/s41392-022-01023-wDOI Listing
June 2022

Connexins and angiogenesis: Functional aspects, pathogenesis, and emerging therapies (Review).

Int J Mol Med 2022 Aug 28;50(2). Epub 2022 Jun 28.

Department of Cardio‑Thoracic Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, P.R. China.

Connexins (Cxs) play key roles in cellular communication. By facilitating metabolite exchange or interfering with distinct signaling pathways, Cxs affect cell homeostasis, proliferation, and differentiation. Variations in the activity and expression of Cxs have been linked to numerous clinical conditions including carcinomas, cardiac disorders, and wound healing. Recent discoveries on the association between Cxs and angiogenesis have sparked interest in Cx‑mediated angiogenesis due to its essential functions in tissue formation, wound repair, tumor growth, and metastasis. It is now widely recognized that understanding the association between Cxs and angiogenesis may aid in the development of new targeted therapies for angiogenic diseases. The aim of the present review was to provide a comprehensive overview of Cxs and Cx‑mediated angiogenesis, with a focus on therapeutic implications.
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http://dx.doi.org/10.3892/ijmm.2022.5166DOI Listing
August 2022

Characterization of Developmental Neurobehavioral Toxicity in a Zebrafish MPTP-Induced Model: A Novel Mechanism Involving Anemia.

ACS Chem Neurosci 2022 Jun 27. Epub 2022 Jun 27.

School of Public Health and Preventive Medicine, Wenzhou Medical University, Wenzhou 325035, China.

Zebrafish represent an economical alternative to rodents for developmental neurotoxicity (DNT) testing. Mechanistic understanding is the key to successfully translating zebrafish findings to humans. In the present study, we used a well-known dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model chemical to uncover the molecular pathways for observed DNT effects. To enhance the specificity of potential molecular targets, we restricted our exposure to a concentration that is nonteratogenic yet exhibits high DNT effects and an exposure window sensitive to MPTP. Our DNT assessment based on a battery of motor and social behavioral tests revealed an effective concentration of 1 μM and a sensitive window of 48-96 h postfertilization (hpf) for MPTP-induced hypoactivity. It is worth noting that this hypoactivity persisted into later larval development until 28 dpf. We observed increased cell apoptosis, oxidative stress, and decreased ATP levels in larvae immediately after exposure at 96 hpf. Significant reductions of DA neurons were found in the retina at 72, 96, and 120 hpf. No visible deformity was found in motoneurons at 72, 96, and 120 hpf. Transcriptome analysis uncovered a novel pathway manifested by significant upregulation of genes enriched with erythropoiesis. Sensitive window exposure of MPTP and other DA neurotoxins rotenone and paraquat exhibited a concentration-dependent effect on transcriptional changes of embryonic hemoglobins and anemia. Given that anemia is a significant risk factor for Parkinson's disease and MPTP is known to cause parkinsonism in humans, we concluded that anemia resulting from dysregulation of primitive erythropoiesis during embryonic development might serve as a common mechanism underlying DA neurotoxin-induced DNT effects between zebrafish and humans.
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http://dx.doi.org/10.1021/acschemneuro.2c00089DOI Listing
June 2022

Development and validation of a nomogram to assess postoperative venous thromboembolism risk in patients with stage IA non-small cell lung cancer.

Cancer Med 2022 Jun 27. Epub 2022 Jun 27.

Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Background: Venous thromboembolism (VTE) is a common postoperative complication in patients with lung cancer that seriously affects prognosis and quality of life. At present, the detection rate of patients with early-stage lung cancer is increasing, but there are few studies on the risk factors for postoperative venous thromboembolism (VTE) in patients with stage IA non-small cell lung cancer (NSCLC). This study aimed to establish a nomogram for predicting the probability of postoperative VTE risk in patients with stage IA NSCLC.

Methods: The clinical data of 452 patients with stage IA NSCLC from January 2017 to January 2022 in our center were retrospectively analyzed and randomly divided into a training set and a validation set at a ratio of 7:3. Independent risk factors were identified by univariate and multivariate logistic regression analyses, and a nomogram was established based on the results and internally validated. The predictive power of the nomogram was evaluated by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).

Results: The nomogram prediction model included three risk factors: age, preoperative D-dimer, and intermuscular vein dilatation. The areas under the ROC curve of this predictive model were 0.832 (95% CI: 0.732-0.924) and 0.791 (95% CI: 0.668-0.930) in the training and validation sets, respectively, showing good discriminative power. In addition, the probability of postoperative VTE occurrence predicted by the nomogram was consistent with the actual occurrence probability. In the decision curve, the nomogram model had a better net clinical benefit at a threshold probability of 5%-90%.

Conclusion: This study is the first to develop a nomogram for predicting the risk of postoperative VTE in patients with stage IA NSCLC; this nomogram can accurately and intuitively evaluate the probability of VTE in these patients and help clinicians make decisions on prevention and treatment.
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http://dx.doi.org/10.1002/cam4.4982DOI Listing
June 2022

Safety evaluation of the food enzyme glucan 1,4-α-maltohydrolase from the genetically modified strain NZYM-FR.

EFSA J 2022 Jun 15;20(6):e07367. Epub 2022 Jun 15.

The food enzyme glucan 1,4-α-maltohydrolase (4-α-d-glucan α-maltohydrolase; 3.2.1.133) is produced with the genetically modified strain NZYM-FR by Novozymes A/S. The genetic modifications did not give rise to safety concerns. The production strain has been shown to qualify for Qualified Presumption of Safety (QPS) status. The food enzyme is free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in three food manufacturing processes, namely baking and brewing processes and starch processing for glucose syrup production and other starch hydrolysates. Since residual amounts of total organic solids (TOS) are removed by the purification steps applied during the production of glucose syrups, dietary exposure was calculated only for the baking and brewing processes. Dietary exposure was estimated to be up to 0.30 mg TOS/kg body weight (bw) per day in European populations. Given the QPS status of the production strain and the lack of hazards resulting from the food enzyme manufacturing process, toxicological studies were not considered necessary. Similarity of the amino acid sequence to those of known allergens was searched and four matches were found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood of such reactions to occur is considered to be low. Based on the data provided, the QPS status of the production strain and the absence of issues arising from the production process, the Panel concluded that the food enzyme glucan 1,4-α-maltohydrolase produced with the genetically modified strain NZYM-FR does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2022.7367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199875PMC
June 2022

Safety evaluation of the food enzyme glucan 1,4-α-maltohydrolase from the genetically modified strain NZYM-CY.

EFSA J 2022 Jun 16;20(6):e07366. Epub 2022 Jun 16.

The food enzyme glucan 1,4-α-maltohydrolase (4-α-d-glucan α-maltohydrolase; 3.2.1.133) is produced with the genetically modified strain NZYM-CY by Novozymes A/S. The genetic modifications did not give rise to safety concerns. The production strain has been shown to qualify for Qualified Presumption of Safety (QPS) status. The food enzyme is free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in three food manufacturing processes, namely baking and brewing processes and starch processing for glucose syrup production and other starch hydrolysates. Since residual amounts of total organic solids (TOS) are removed by the purification steps applied during the production of glucose syrups, dietary exposure was calculated only for the baking and brewing processes. Dietary exposure was estimated to be up to 0.45 mg TOS/kg body weight (bw) per day in European populations. Given the QPS status of the production strain and the lack of hazards resulting from the food enzyme manufacturing process, toxicological studies were not considered necessary. Similarity of the amino acid sequence to those of known allergens was searched and four matches were found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood of such reactions to occur is considered to be low. Based on the data provided, the QPS status of the production strain and the absence of issues arising from the production process, the Panel concluded that the food enzyme glucan 1,4-α-maltohydrolase produced with the genetically modified strain NZYM-CY does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2022.7366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202445PMC
June 2022

Safety evaluation of the food enzyme glucan 1,4-α-maltohydrolase from the genetically modified strain NZYM-SD.

EFSA J 2022 Jun 15;20(6):e07368. Epub 2022 Jun 15.

The food enzyme glucan 1,4-α-maltohydrolase (4-α-d-glucan α-maltohydrolase; 3.2.1.133) is produced with the genetically modified strain NZYM-SD by Novozymes A/S. The genetic modifications did not give rise to safety concerns. The production strain has been shown to qualify for Qualified Presumption of Safety (QPS) status. The food enzyme is free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in three food manufacturing processes, namely baking processes and brewing processes and starch processing for glucose syrup production and other starch hydrolysates. Since residual amounts of total organic solids (TOS) are removed by the purification steps applied during the production of glucose syrups, dietary exposure was calculated only for baking and brewing processes. Dietary exposure was estimated to be up to 0.57 mg TOS/kg body weight (bw) per day in European populations. Given the QPS status of the production strain and the lack of hazards resulting from the food enzyme manufacturing process, toxicological studies were not considered necessary. Similarity of the amino acid sequence to those of known allergens was searched and four matches were found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood of such reactions to occur is considered to be low. Based on the data provided, the QPS status of the production strain and the absence of issues arising from the production process, the Panel concluded that the food enzyme glucan 1,4-α-maltohydrolase produced with the genetically modified strain NZYM-SD does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2022.7368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200369PMC
June 2022

Analysis of Microbial Community, Volatile Flavor Compounds, and Flavor of Cigar Tobacco Leaves From Different Regions.

Front Microbiol 2022 10;13:907270. Epub 2022 Jun 10.

School of Biotechnology, Jiangnan University, Wuxi, China.

Despite the booming international trade in cigar tobacco leaves (CTLs), the main characteristics of tobacco leaves from different producing areas are rarely reported. This study aimed to characterize the microbial community, volatile flavor compounds (VFCs), and flavor of CTLs from four famous cigar-producing areas, including Dominica, Brazil, Indonesia, and China. High-throughput sequencing results showed that the dominant genera in CTLs were , and . Sensory analysis revealed that Indonesian and Chinese CTLs were characterized by leathery, peppery, and baked aroma. Brazilian CTLs were dominated by caramel and herb aroma. Dominican CTLs had aromas of milk, fruity, sour, cream, flower, nutty, and honey. Supplemented with the determination of volatile flavor compounds (VFCs), the flavor of CTLs could be scientifically quantified. Most of these VFCs were aldehydes and ketones, and 20 VFCs showed significant differences in CTLs from different regions. The microbial community, VFCs, and flavor of CTLs vary widely due to geographic differences. Network analysis revealed the microbial community was closely related to most VFCs, but the relationships between the fungal community and VFCs were less than the bacterial community, and most of them were negative. Furthermore, it also found that the bacterial community had a greater contribution to the flavor of CTLs than the fungal community. This study obtained essential information on CTLs, which laid a foundation for deeply excavating the relationship between microbes and VFCs and flavor, and establishing a tobacco information database.
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http://dx.doi.org/10.3389/fmicb.2022.907270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231593PMC
June 2022

Resurgence of H5N6 avian influenza virus in 2021 poses new threat to public health.

Lancet Microbe 2022 Jun 21. Epub 2022 Jun 21.

Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; National Avian Influenza Para-reference Laboratory, Guangzhou, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, National Development and Reform Commission of the People's Republic of China, Guangzhou, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Guangzhou, China; Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/S2666-5247(22)00148-3DOI Listing
June 2022

Incorporating an Aromatic Cationic Spacer to Assemble 2D Polar Perovskite Crystals toward Self-Powered Detection of Quite Weak Polarized Light.

J Phys Chem Lett 2022 Jun 24:6017-6023. Epub 2022 Jun 24.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.

Two-dimensional (2D) hybrid perovskites with intrinsic attributes of structural and optical anisotropy are holding a bright promise for polarization-sensitive photodetection. However, studies on self-powered detection to quite weak polarized light remain scarce in this 2D family. By incorporating an aromatic spacer into the 3D cubic prototype, we have successfully assembled a new 2D hybrid perovskite with a polar motif, (FPEA)(MA)PbI (, where FPEA is 4-fluorophenethylammonium and MA is methylammonium). Its unique 2D quantum-well structure allows optical absorption dichroism with a large ratio of ∼3.15, and the natural polarity results in a notable bulk photovoltaic effect. Further, centimeter-size crystals (10 × 10 × 3 mm) of were facilely obtained by the temperature cooling method, and its crystal-based detectors enable excellent self-powered detection of quite weak polarized light, showing a notable polarization-sensitive ratio (∼1.5), extremely low detection limit (∼100 nW/cm), and antifatigued stability. The alloyed aromatic cationic spacers facilitate the polarity and enhanced phase stability. This study paves a way for further exploration of new 2D perovskite candidates toward optoelectronic device applications.
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http://dx.doi.org/10.1021/acs.jpclett.2c01435DOI Listing
June 2022

LPG-PCFG: An Improved Probabilistic Context- Free Grammar to Hit Low-Probability Passwords.

Sensors (Basel) 2022 Jun 18;22(12). Epub 2022 Jun 18.

Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, China.

With the development of the Internet, information security has attracted more attention. Identity authentication based on password authentication is the first line of defense; however, the password-generation model is widely used in offline password attacks and password strength evaluation. In real attack scenarios, high-probability passwords are easy to enumerate; extremely low-probability passwords usually lack semantic structure and, so, are tough to crack by applying statistical laws in machine learning models, but these passwords with lower probability have a large search space and certain semantic information. Improving the low-probability password hit rate in this interval is of great significance for improving the efficiency of offline attacks. However, obtaining a low-probability password is difficult under the current password-generation model. To solve this problem, we propose a low-probability generator-probabilistic context-free grammar (LPG-PCFG) based on PCFG. LPG-PCFG directionally increases the probability of low-probability passwords in the models' distribution, which is designed to obtain a degeneration distribution that is friendly for generating low-probability passwords. By using the control variable method to fine-tune the degeneration of LPG-PCFG, we obtained the optimal combination of degeneration parameters. Compared with the non-degeneration PCFG model, LPG-PCFG generates a larger number of hits. When generating 107 and 108 times, the number of hits to low-probability passwords increases by 50.4% and 42.0%, respectively.
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http://dx.doi.org/10.3390/s22124604DOI Listing
June 2022

Identification of miRNAs in Response to Sweet Potato Weevil () Infection by sRNA Sequencing.

Genes (Basel) 2022 May 30;13(6). Epub 2022 May 30.

Institute of Food Crops, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.

The sweet potato weevil () is an important pest in the growing and storage of sweet potatoes. It is a common pest in the sweet potato production areas of southern China, causing serious harm to the development of the sweet potato industry. For the existing cultivars in China and abroad, there is no sweet potato variety with complete resistance to the sweet potato weevil. Thus, understanding the regulation mechanisms of sweet potato weevil resistance is the prerequisite for cultivating sweet potato varieties that are resistant to the sweet potato weevil. However, very little progress has been made in this field. In this study, we inoculated adult sweet potato weevils into sweet potato tubers. The infected sweet potato tubers were collected at 0, 24, 48, and 72 h. Then, a miRNA library was constructed for Eshu 6 and Guang 87 sweet potato tubers infected for different lengths of time. A total of 407 known miRNAs and 298 novel miRNAs were identified. A total of 174 differentially expressed miRNAs were screened out from the known miRNAs, and 247 differentially expressed miRNAs were screened out from the new miRNAs. Moreover, the targets of the differentially expressed miRNAs were predicted and their network was further investigated through GO analysis and KEGG analysis using our previous transcriptome data. More importantly, we screened 15 miRNAs and their target genes for qRT-PCR verification to confirm the reliability of the high-throughput sequencing data, which indicated that these miRNAs were detected and most of the expression results were consistent with the sequencing results. These results provide theoretical and data-based resources for the identification of miRNAs in response to sweet potato weevil infection and an analysis of the molecular regulatory mechanisms involved in insect resistance.
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http://dx.doi.org/10.3390/genes13060981DOI Listing
May 2022

Fermatean Fuzzy Schweizer-Sklar Operators and BWM-Entropy-Based Combined Compromise Solution Approach: An Application to Green Supplier Selection.

Entropy (Basel) 2022 May 31;24(6). Epub 2022 May 31.

Department of Logistics, University of Defence in Belgrade, 11000 Belgrade, Serbia.

The Fermatean fuzzy set (FFS) is a momentous generalization of a intuitionistic fuzzy set and a Pythagorean fuzzy set that can more accurately portray the complex vague information of elements and has stronger expert flexibility during decision analysis. The Combined Compromise Solution (CoCoSo) approach is a powerful decision-making technique to choose the ideal objective by fusing three aggregation strategies. In this paper, an integrated, multi-criteria group-decision-making (MCGDM) approach based on CoCoSo and FFS is used to assess green suppliers. To begin, several innovative operations of Fermatean fuzzy numbers based on Schweizer-Sklar norms are presented, and four aggregation operators utilizing the proposed operations are also developed. Several worthwhile properties of the advanced operations and operators are explored in detail. Next, a new Fermatean fuzzy entropy measure is propounded to determine the combined weight of criteria, in which the subjective and objective weights are computed by an improved best-and-worst method (BWM) and entropy weight approach, respectively. Furthermore, MCGDM based on CoCoSo and BWM-Entropy is brought forward and employed to sort diverse green suppliers. Lastly, the usefulness and effectiveness of the presented methodology is validated by comparison, and the stability of the developed MCGDM approach is shown by sensitivity analysis. The results shows that the introduced method is more stable during ranking of green suppliers, and the comparative results expound that the proposed method has higher universality and credibility than prior Fermatean fuzzy approaches.
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http://dx.doi.org/10.3390/e24060776DOI Listing
May 2022

Optimal Policy of Multiplayer Poker via Actor-Critic Reinforcement Learning.

Entropy (Basel) 2022 May 30;24(6). Epub 2022 May 30.

Department of Automation, Tsinghua University, Beijing 100084, China.

Poker has been considered a challenging problem in both artificial intelligence and game theory because poker is characterized by imperfect information and uncertainty, which are similar to many realistic problems like auctioning, pricing, cyber security, and operations. However, it is not clear that playing an equilibrium policy in multi-player games would be wise so far, and it is infeasible to theoretically validate whether a policy is optimal. Therefore, designing an effective optimal policy learning method has more realistic significance. This paper proposes an optimal policy learning method for multi-player poker games based on Actor-Critic reinforcement learning. Firstly, this paper builds the Actor network to make decisions with imperfect information and the Critic network to evaluate policies with perfect information. Secondly, this paper proposes a novel multi-player poker policy update method: asynchronous policy update algorithm (APU) and dual-network asynchronous policy update algorithm (Dual-APU) for multi-player multi-policy scenarios and multi-player sharing-policy scenarios, respectively. Finally, this paper takes the most popular six-player Texas hold 'em poker to validate the performance of the proposed optimal policy learning method. The experiments demonstrate the policies learned by the proposed methods perform well and gain steadily compared with the existing approaches. In sum, the policy learning methods of imperfect information games based on Actor-Critic reinforcement learning perform well on poker and can be transferred to other imperfect information games. Such training with perfect information and testing with imperfect information models show an effective and explainable approach to learning an approximately optimal policy.
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http://dx.doi.org/10.3390/e24060774DOI Listing
May 2022

Genome-wide identification of cold-tolerance genes and functional analysis of IbbHLH116 gene in sweet potato.

Gene 2022 Jun 20;837:146690. Epub 2022 Jun 20.

Research Center of Crop Stresses Resistance Technologies/ Engineering Research Centre of Ecology and Agricultural Use of Wetland, Ministry of Education, Yangtze University, Jingzhou 434025, China. Electronic address:

Sweet potato (Ipomoea batatas L.) originated from South America; therefore, it is vulnerable to low temperature. Here, the evolutionary analysis of 22 cold-responsive genes in 35 plant species revealed that the identified MYC-type basic helix-loop-helix (bHLH) transcription factors exhibit diverse structures. We found that the number of bHLH gene family members was significantly lower than that of cold-tolerant species. We further systematically evaluated the gene structure, promoter analysis, synteny analysis, and expression pattern of 28 bHLH gene family members in sweet potato. The basic helix-loop-helix protein 116 (IbbHLH116) has the closest phylogeny to the AtICE1 protein of A. thaliana. However, the IbbHLH116 protein from cold-tolerant variety FS18 showed a 37.90% of sequence homology with AtICE1 protein. Subcellular localization analysis showed that IbbHLH116 is localized in the nucleus. The transcripts of IbbHLH116 were highly accumulated in cold-tolerant genotype FS18, particularly in new leaves and stems, compared to the cold-sensitive genotype NC1 under cold stress. Overexpression of IbbHLH116 in the wild type (Col-0) A. thaliana significantly enhanced cold tolerance in transgenic plants by regulating activities of oxidative protective enzymes, such as peroxidase (POD), superoxide dismutase (SOD), and the contents of malondialdehyde (MDA), proline and soluble proteins. Moreover, overexpression of IbbHLH116 in ice1 mutant A. thaliana fully rescued the cold-sensitive phenotype by promoting the expression of C-repeat binding factors 3 (CBF3). Overexpression of IbbHLH116 in the sweet potato callus also induced the expression of CBF3 under low temperature. These results imply that IbbHLH116 can perform the function of the ICE1 gene in conferring cold tolerance in sweet potato.
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http://dx.doi.org/10.1016/j.gene.2022.146690DOI Listing
June 2022

Short and long-term outcomes between laparoscopic and open total gastrectomy for advanced gastric cancer after neoadjuvant chemotherapy.

World J Gastrointest Surg 2022 May;14(5):452-469

Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.

Background: Neoadjuvant chemotherapy (NACT) combined with surgery is regarded as an effective treatment for advanced gastric cancer (AGC). Laparoscopic surgery represents the mainstream of minimally invasive surgery. Currently, surgeons focus more on surgical safety and oncological outcomes of laparoscopic gastrectomy after NACT. Thus, we sought to evaluate short- and long-term outcomes between laparoscopic total gastrectomy (LTG) and open total gastrectomy (OTG) after NACT.

Aim: To compare the short and long-term outcomes between LTG and OTG for AGC after NACT.

Methods: We retrospectively collected the clinicopathological data of 136 patients who accepted gastrectomy after NACT from June 2012 to June 2019, including 61 patients who underwent LTG and 75 who underwent OTG. Clinicopathological characteristics between the LTG and OTG groups showed no significant difference. SPSS 26.0, R software, and GraphPad PRISM 8.0 were used to perform statistical analyses.

Results: Of the 136 patients included, eight acquired pathological complete response, and the objective response rate was 47.8% (65/136). The LTG group had longer operation time ( = 0.015), less blood loss ( = 0.003), shorter days to first flatus ( < 0.001), and shorter postoperative hospitalization days ( < 0.001). LTG spent more surgical cost than OTG ( < 0.001), while total hospitalized cost of LTG was less than OTG ( < 0.001). 21 (28.0%) patients in the OTG group and 14 (23.0%) in the LTG group had 30-d postoperative complications, but there was no significant difference between the two groups ( = 0.503). The 3-year overall survival (OS) rate was 60.6% and 64.6% in the LTG and OTG groups, respectively [hazard ratio (HR) = 0.859, 95% confidence interval (CI): 0.522-1.412, = 0.546], while the 3-year disease-free survival (DFS) rate was 54.5% and 51.8% in the LTG and OTG group, respectively (HR = 0.947, 95%CI: 0.582-1.539, = 0.823). Multivariate cox analysis showed that body mass index and pTNM stage were independent risk factors for OS while vascular invasion and pTNM stage were independent risk factors for DFS ( < 0.05).

Conclusion: After NACT, LTG shows comparable 30-d postoperative morbidity as well as 3-year OS and DFS rate to OTG. We recommend that experienced surgeons select LTG other than OTG for proper AGC patients after NACT.
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http://dx.doi.org/10.4240/wjgs.v14.i5.452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160691PMC
May 2022

Safety evaluation of the food enzyme pullulanase from the genetically modified strain NZYM-LU.

EFSA J 2022 Jun 14;20(6):e07359. Epub 2022 Jun 14.

The food enzyme pullulanase (pullulan 6-α-glucanohydrolase, EC 3.2.1.41) is produced with the genetically modified strain NZYM-LU by Novozyme A/S. The genetic modifications did not give rise to safety concerns. The production strain has been shown to qualify for the qualified presumption of safety (QPS) status. The food enzyme was considered free from viable cells of the production organism and its DNA. It is intended to be used in brewing processes and in starch processing for production of glucose syrups and other starch hydrolysates. Since residual amounts of total organic solids (TOS) are removed by the purification steps applied during the production of glucose syrups, dietary exposure was calculated only for the brewing processes. It was estimated to be up to 0.59 mg TOS/kg body weight (bw) per day in European populations. Given the QPS status of the production strain and the lack of hazards resulting from the food enzyme manufacturing process, toxicological studies were not considered necessary. The similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is low. Based on the data provided, the QPS status of the production strain and the absence of issues of concern arising from the production process, the Panel concluded that the food enzyme pullulanase produced with the genetically modified  strain NZYM-LU does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2022.7359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194765PMC
June 2022

Safety evaluation of the food enzyme endo-1,4-β-xylanase from the genetically modified strain NZYM-ER.

EFSA J 2022 Jun 13;20(6):e07373. Epub 2022 Jun 13.

The food enzyme endo-1,4-β-xylanase (4-β-d-xylan xylanohydrolase; EC 3.2.1.8) is produced with the genetically modified strain NZYM-ER by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is considered free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in brewing processes, distilled alcohol production, grain treatment for the production of starch and gluten fractions and for palm oil production. Since residual amounts of total organic solids (TOS) are removed by distillation, in palm oil production and in grain treatment for the production of starch and gluten fraction, dietary exposure was only calculated for brewing processes. Dietary exposure to the food enzyme TOS was estimated to be up to 0.09 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1,051 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, results in a margin of exposure of at least 11,400. A search for similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that, under the intended conditions of use (other than distilled alcohol production) the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2022.7373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190295PMC
June 2022

AdipoR1 Regulates Ionizing Radiation-Induced Ferroptosis in HCC cells through Nrf2/xCT Pathway.

Oxid Med Cell Longev 2022 13;2022:8091464. Epub 2022 Jun 13.

School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.

Radiotherapy has been used for decades in the treatment of liver cancer. We previously found that adiponectin receptor (AdipoR1) is a prognostic biomarker for hepatoma carcinoma (HCC) after stereotactic body radiation therapy (SBRT) and blocking AdipoR1 enhances radiation sensitivity in hepatoma carcinoma cells. In the current study, we aimed to elucidate the roles of AdipoR1 in ionizing radiation- (IR-) induced radiosensitivity by activating ferroptosis pathway in HCC cells. We found that IR upregulated the expression of AdipoR1 and furthermore promoted the protein stability of transcription factor Nrf2, Nrf2 binded to the xCT promoter and increased xCT transcription and expression, and this directly contributed to the protective function in the early stage of radiation in HCC cells. AdipoR1 knockdown significantly inhibited expression of Nrf2 and xCT and, furthermore, increased both IR- and erastin-induced ferroptosis, which could be abolished by the rescue of Nrf2 and xCT. For the first time, we found that radiation-induced ferroptosis was mediated by AdipoR1-Nrf2-xCT pathway in HCC cells. These results provide new insights to the development and application of novel therapeutic strategies for hepatoma carcinoma.
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http://dx.doi.org/10.1155/2022/8091464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208988PMC
June 2022

Design, Synthesis, and Optimization of Macrocyclic Peptides as Species-Selective Antimalaria Proteasome Inhibitors.

J Med Chem 2022 Jun 21. Epub 2022 Jun 21.

Department of Microbiology & Immunology, Weill Cornell Medicine, 1300 York Ave., New York, New York 10065, United States.

With over 200 million cases and close to half a million deaths each year, malaria is a threat to global health, particularly in developing countries. , the parasite that causes the most severe form of the disease, has developed resistance to all antimalarial drugs. Resistance to the first-line antimalarial artemisinin and to artemisinin combination therapies is widespread in Southeast Asia and is emerging in sub-Saharan Africa. The proteasome is an attractive antimalarial target because its inhibition kills the parasite at multiple stages of its life cycle and restores artemisinin sensitivity in parasites that have become resistant through mutation in Kelch K13. Here, we detail our efforts to develop noncovalent, macrocyclic peptide malaria proteasome inhibitors, guided by structural analysis and pharmacokinetic properties, leading to a potent, species-selective, metabolically stable inhibitor.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00611DOI Listing
June 2022

The safety and efficacy of laparoscopic gastrectomy for patients with locally advanced gastric cancer following neoadjuvant chemotherapy.

Sci Rep 2022 Jun 20;12(1):10384. Epub 2022 Jun 20.

Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.

Limited researches focused on the application of laparoscopic gastrectomy (LG) in locally advanced gastric cancer (LAGC) patients following neoadjuvant chemotherapy (NACT). In this study, we aimed at illustrating the surgical and survival outcome of LG in LAGC patients following NACT. We performed a retrospective study of patients with LAGC who received either LG following NACT or upfront LG at Fujian Provincial Hospital between March 2013 and October 2018. Perioperative parameters, short-term and long-term outcomes were compared. The Kaplan-Meier estimator was used to describe the survival curves, and the differences were examined by the log-rank test. In total, 76 consecutive patients were enrolled into the NACT-LG (41 patients) and LG (35 patients) group. The postoperative hospital stay was significantly longer for LG than for NACT-LG (11.0 vs. 12.0 day, P = 0.031). Significant difference was found in Grade ≥ III severe postoperative complications in two groups (0 vs. 17.1%, P = 0.001). No patient died of postoperative complications in the NACT-LG group, and one patient (1/35, 2.9%) died of postoperative complications in the LG group. A forest plot revealed that most subgroups of LG group were at great risks of postoperative complications. Compared with the LG group, the NACT-LG group had a significantly better DFS (14.4% vs. 5.7%, P = 0.0299) and better OS (34.1% vs. 8.6%, P = 0.0061) at 3 years. NACT increased the safety of LG for patients with LAGC and offer better disease-free and overall survival. For patients with LAGC, LG following NACT should be the priority treatment.
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http://dx.doi.org/10.1038/s41598-022-14717-6DOI Listing
June 2022

Bismuth Coordinates with Iodine Atoms to Form Chemical Bonds for Existing Stabilization in Boron Glass.

Inorg Chem 2022 Jun 20. Epub 2022 Jun 20.

State Key Laboratory of Environment-Friendly Energy Materials, Southwest University of Science and Technology, Mianyang 621010, P. R. China.

Stabilizing radioactive iodine in boron glass for disposal was the ultimate goal of this study. In this study, bismuth was used near a monument. Thermogravimetric analysis showed that bismuth could remarkably stabilize iodine atoms in boron glass (only 3.74% of the mass was lost at 850 °C). Scanning electron microscopy-energy dispersive spectrometry images showed that most of the AgI was uniformly immobilized in the glass network. X-ray photoelectron spectrometry and NMR results confirmed the change in the coordination number of boron in the samples. The density functional theory calculation helped to understand the reason for the stable presence of iodine in boron glass. Iodine atoms were difficult to bond directly with boron atoms but tended to bond with bismuth atoms. From the spatial distribution of the structural molecular orbitals, it was observed that the bismuth atom releases electrons when stimulated, and the iodine atom needs to gain an electron to reach stability. At a low treatment temperature of 550 °C, the maximum density of the immobilized sample containing bismuth is 2.42 g·cm, and its iodine leaching rate at day 7 can be as low as 3.77 × 10 g·m·d. This study provides a way to improve the properties of boron glass microscopically in the future.
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http://dx.doi.org/10.1021/acs.inorgchem.1c03680DOI Listing
June 2022

Erratum: Tumor Theranostics of Transition Metal Ions Loaded Polyaminopyrrole Nanoparticles: Erratum.

Nanotheranostics 2022 18;6(3):322-324. Epub 2022 Feb 18.

State Key Supramolecular Structure and Materials Laboratory, College of Chemistry, Jilin University, Changchun 130012, P. R. China.

[This corrects the article DOI: 10.7150/ntno.25119.].
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http://dx.doi.org/10.7150/ntno.67620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194588PMC
February 2022

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis.

Comput Math Methods Med 2022 8;2022:7858925. Epub 2022 Jun 8.

Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.

Background: Gubitong Recipe (GBT) is a prescription based on the Traditional Chinese Medicine (TCM) theory of tonifying the kidney yang and strengthening the bone. A previous multicentral randomized clinical trial has shown that GBT can effectively relieve joint pain and improve quality of life with a high safety in treating osteoarthritis (OA). This study is aimed at elucidating the active compounds, potential targets, and mechanisms of GBT for treating OA.

Method: The network pharmacology method was used to predict the key active compounds, targets, and mechanisms of GBT in treating OA. An OA rat model was established with Hulth surgery, and the pathological changes of articular cartilage were observed to evaluate the effects of GBT. Chondrocytes were stimulated with LPS to establish in vitro models, and key targets and mechanisms predicted by network pharmacology were verified via qRT-PCR, ELISA, western blot, and immunofluorescence. The Contribution Index Model and molecular docking were used to determine the key active compounds of GBT and the major nodes affecting predicted pathways.

Result: A total of 500 compounds were acquired from related databases, where 87 active compounds and their 254 corresponding targets were identified. 2979 OA-related genes were collected from three databases, 150 of which were GBT-regulating OA genes. The compound-target network weight analysis and PPI results showed that IL-6 and PGE are key targets of GBT in treating OA. KEGG results showed that PI3K/AKT, Toll-like receptor, NFB, TNF, and HIF-1 are the key signaling pathways. An in vivo experiment showed that GBT could effectively suppress cartilage degradation of OA rats. In vitro experiments demonstrated that GBT can inhibit the key targets of KEGG-related pathways. Molecular-docking results suggested that luteolin, licochalcone A, and -carotene were key targets of GBT, and the mechanisms may be associated with the NFB signaling pathway. Blockage experiments showed that the NFB pathway is the key pathway of GBT in treating OA.

Conclusion: This study verified that GBT can effectively protect articular cartilage through multitarget and multipathway, and its inhibitory effect on the NFB pathway is the most key mechanism in treating OA.
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http://dx.doi.org/10.1155/2022/7858925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200584PMC
June 2022

Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials.

J Biol Chem 2022 Jun 16:102151. Epub 2022 Jun 16.

MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, SW7 2AZ, UK. Electronic address:

Antimicrobial tolerance, the ability to survive exposure to antimicrobials via transient nonspecific means, promotes the development of antimicrobial resistance (AMR). The study of the molecular mechanisms that result in antimicrobial tolerance is therefore essential for the understanding of AMR. In gram-negative bacteria, the second messenger molecule 3',5'-cyclic adenosine monophosphate (cAMP) has been previously shown to be involved in AMR. In mycobacteria, however, the role of cAMP in antimicrobial tolerance has been difficult to probe due to its particular complexity. In order to address this difficulty, here, through an unbiased biochemical approaches consisting in the fractionation of clear protein lysate from a mycobacterial strain deleted for the known cAMP phosphodiesterase (Rv0805c) combined with mass spectrometry techniques, we identified a novel cyclic nucleotide-degrading phosphodiesterase enzyme (Rv1339) and developed a system to significantly decrease intracellular cAMP levels through plasmid expression of Rv1339 using the constitutive expression system, pVV16. In Mycobacterium smegmatis mc155, we demonstrate that recombinant expression of Rv1339 reduced cAMP levels 3-fold and resulted in altered gene expression, impaired bioenergetics and a disruption in peptidoglycan biosynthesis leading to decreased tolerance to antimicrobials that target cell wall synthesis such as ethambutol, D-cycloserine and vancomycin. This work increases our understanding of the role of cAMP in mycobacterial antimicrobial tolerance and our observations suggest that nucleotide signaling may represent a new target for the development of antimicrobial therapies.
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http://dx.doi.org/10.1016/j.jbc.2022.102151DOI Listing
June 2022

The regulatory effect of pulmonary lymphatic drainage on silicosis fibrosis.

Ecotoxicol Environ Saf 2022 Jun 15;241:113758. Epub 2022 Jun 15.

School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address:

Silicosis is a fibrotic disease caused by long-term inhalation of SiO particles that currently has no effective treatment. Earlier studies have suggested that pulmonary lymphatic vessels play a key role in the transport of silica but have not address the long-term effects of altered pulmonary lymphatic drainage on silicosis. Here, we investigated the impact of impaired pulmonary lymphatic drainage on silicosis. In the past, lymphatic drainage disorders were established mainly through the use of VEGF inhibitors. For the first time, we established a model of pulmonary lymphatic drainage disorder by ligating the thoracic duct in rats. Impaired pulmonary lymphatic drainage was found to aggravate inflammation and oxidative damage in silicosis rats and accelerate silicosis progression. Next, we investigated the effect of pulmonary lymphatic drainage on silicosis. We have demonstrated the effect of sodium tanshinone IIA sulfonate(STS) on lymphangiogenesis, which revealed that STS promotes lymphangiogenesis and can delay inflammation, oxidative damage, and fibrosis progression in silicosis rats by promoting the pulmonary lymphatic drainage response, and this effect is mediated by the VEGFR-3/PI3K/AKT signaling pathway. These findings suggest that pulmonary lymphogenesis plays an important role in silicosis pathogenesis, and targeted intervention in pulmonary lymphangiogenesis may be a potential strategy for treating of silicosis in the future.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113758DOI Listing
June 2022
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