ISSN 0253-2778

CN 34-1054/N

Life Sciences

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Structural knowledge error, rather than reward insensitivity, explains the reduced metacontrol in aging
Zhaoyu Zuo, Lizhuang Yang, Hai Li
2023, 53(12): 1203. doi: 10.52396/JUSTC-2023-0132
Abstract:
Humans flexibly adjust their reliance on model-free (habitual) and model-based (goal-directed) strategies according to cost‒benefit trade-offs, the ability of which is known as metacontrol. Recent studies have suggested that older adults show reduced flexibility in metacontrol. However, whether the metacontrol deficit in aging is due to cognitive or motivational factors remains ambiguous. The present study investigated this issue using pupillometry recording and a sequential decision-making task with varied task structures and reward stakes. Our results revealed that older adults performed less model-based control and less flexibility when the reward stake level changed, consistent with previous studies. However, pupillometry analysis indicated that older adults showed comparable sensitivity to the reward stake. Older adults varied in task structure knowledge according to their oral reports, and the subgroup with good structural knowledge exerted a similar pattern to younger adults. Computational simulation verified that poor structure knowledge representation impaired metacontrol. These results suggest that the inflexible metacontrol in the elderly population might not be due to motivational factors but rather poor structure knowledge. Humans flexibly adjust their reliance on model-free (habitual) and model-based (goal-directed) strategies according to cost‒benefit trade-offs, the ability of which is known as metacontrol. Recent studies have suggested that older adults show reduced flexibility in metacontrol. However, whether the metacontrol deficit in aging is due to cognitive or motivational factors remains ambiguous. The present study investigated this issue using pupillometry recording and a sequential decision-making task with varied task structures and reward stakes. Our results revealed that older adults performed less model-based control and less flexibility when the reward stake level changed, consistent with previous studies. However, pupillometry analysis indicated that older adults showed comparable sensitivity to the reward stake. Older adults varied in task structure knowledge according to their oral reports, and the subgroup with good structural knowledge exerted a similar pattern to younger adults. Computational simulation verified that poor structure knowledge representation impaired metacontrol. These results suggest that the inflexible metacontrol in the elderly population might not be due to motivational factors but rather poor structure knowledge.
Machine-learning diet quality score and risk of cardiovascular disease
Can Yang, Qi Li, Yan Liu, Ling Zhang, Jian Gao, Xu Steven Xu, Min Yuan
2023, 53(12): 1204. doi: 10.52396/JUSTC-2023-0067
Abstract:
Objectives: Various diet scores have been established to measure overall diet quality, especially for the prevention of cardiovascular disease (CVD). Diet scores constructed by utilizing modern machine learning techniques may contain independent information and can provide better dietary recommendations in combination with the existing diet scores. Methods: We proposed a novel machine-learning diet quality score (DQS) and examined the performance of DQS in combination with the Healthy Eating Index-2015 (HEI2015), Mediterranean Diet Score (MED), Alternative Healthy Eating Index-2010 (AHEI) and Dietary Approaches to Stop Hypertension score (DASH score). The data used in this study were from the 2011–2012 to 2017–2018 cycles of the US National Health and Nutrition Examination Survey (NHANES). Participants aged above 20 self-reported their food intake and information on relevant covariates. We used an elastic-net penalty regression model to select important food features and used a generalized linear regression model to estimate odds ratios (ORs) and 95% CIs after controlling for age, sex, and other relevant covariates. Results: A total of 16756 participants were included in the analysis. DQS was significantly associated with coronary artery disease (CAD) risk after adjusting for one of the other common diet scores. The ORs for DQS combined with the HEI2015, MED, AHEI, and DASH scores were all approximately 0.900, with p values smaller than 0.05. The OR for DQS in the full score model including all other scores was 0.905 (95% CI, 0.828–0.989, p=0.028). Only marginal associations were found between DQS and other CVDs after adjusting for other diet scores. Conclusions: Based on data from four continuous cycles of the NHANES, higher DQS was found to be consistently associated with a lower risk of CAD. The DQS captured unique predictive information independent of the existing diet scores and thus can be used as a complementary scoring system to further improve dietary recommendations for CAD patients. Objectives: Various diet scores have been established to measure overall diet quality, especially for the prevention of cardiovascular disease (CVD). Diet scores constructed by utilizing modern machine learning techniques may contain independent information and can provide better dietary recommendations in combination with the existing diet scores. Methods: We proposed a novel machine-learning diet quality score (DQS) and examined the performance of DQS in combination with the Healthy Eating Index-2015 (HEI2015), Mediterranean Diet Score (MED), Alternative Healthy Eating Index-2010 (AHEI) and Dietary Approaches to Stop Hypertension score (DASH score). The data used in this study were from the 2011–2012 to 2017–2018 cycles of the US National Health and Nutrition Examination Survey (NHANES). Participants aged above 20 self-reported their food intake and information on relevant covariates. We used an elastic-net penalty regression model to select important food features and used a generalized linear regression model to estimate odds ratios (ORs) and 95% CIs after controlling for age, sex, and other relevant covariates. Results: A total of 16756 participants were included in the analysis. DQS was significantly associated with coronary artery disease (CAD) risk after adjusting for one of the other common diet scores. The ORs for DQS combined with the HEI2015, MED, AHEI, and DASH scores were all approximately 0.900, with p values smaller than 0.05. The OR for DQS in the full score model including all other scores was 0.905 (95% CI, 0.828–0.989, p=0.028). Only marginal associations were found between DQS and other CVDs after adjusting for other diet scores. Conclusions: Based on data from four continuous cycles of the NHANES, higher DQS was found to be consistently associated with a lower risk of CAD. The DQS captured unique predictive information independent of the existing diet scores and thus can be used as a complementary scoring system to further improve dietary recommendations for CAD patients.
Association study on bone metabolism in type 2 diabetes by using machine learning
Jiatong Hu, Mingqing Liu, Hongqi Li, Jiayin Yue, Wei Wang, Ji Liu
2023, 53(12): 1205. doi: 10.52396/JUSTC-2023-0089
Abstract:
Type 2 diabetes mellitus is often accompanied by serious complications, including bone metabolic diseases, liver diseases, and kidney diseases, which are affected by the course of disease, sex, age and individual differences and cannot be a unified treatment paradigm. Therefore, for the in-depth analysis of clinical data, looking for the correlation of type 2 diabetes complication data has important guiding significance for the treatment of type 2 diabetes and its complications. In this paper, multiple linear regression models were established based on the clinical data of type 2 diabetes patients in Anhui Province. Our results suggest that the main factors affecting bone complications of type 2 diabetes include body shape indexes, creatinine, uric acid, triglycerides and blood pressure. Interestingly, the bone mineral density of lumbar vertebrae in patients with type 2 diabetes was increased, suggesting that there was a risk of lumbar hyperosteogeny. Type 2 diabetes mellitus is often accompanied by serious complications, including bone metabolic diseases, liver diseases, and kidney diseases, which are affected by the course of disease, sex, age and individual differences and cannot be a unified treatment paradigm. Therefore, for the in-depth analysis of clinical data, looking for the correlation of type 2 diabetes complication data has important guiding significance for the treatment of type 2 diabetes and its complications. In this paper, multiple linear regression models were established based on the clinical data of type 2 diabetes patients in Anhui Province. Our results suggest that the main factors affecting bone complications of type 2 diabetes include body shape indexes, creatinine, uric acid, triglycerides and blood pressure. Interestingly, the bone mineral density of lumbar vertebrae in patients with type 2 diabetes was increased, suggesting that there was a risk of lumbar hyperosteogeny.
The function, structure and dynamic organization of centromeres and kinetochores
Zhen Dou, Ran Liu, Jianye Zang, Xuebiao Yao, Xing Liu
2023, 53(9): 0901. doi: 10.52396/JUSTC-2022-0184
Abstract:
It is a fundamental task to ensure the faithful transmission of genetic information across generations for eukaryote species. The centromere is a specialized chromosomal region that is essential for mediating sister chromatid alignment and separation during mitosis. Centromere identity is epigenetically determined by nucleosome-containing centromere protein A (CENP-A). The CENP-A nucleosome provides the foundation for the association of the inner kinetochore and the assembly of the outer kinetochore in mitosis. Here we review centromere identity determination, inner kinetochore function and assembly, and outer kinetochore function and assembly. In particular, we focus on the recent advances in the structure-activity relationship of the constitutive centromere-associated network (CCAN). CCAN structure information sheds new light on our understanding of centromere and kinetochore functions and dynamic organization. It is a fundamental task to ensure the faithful transmission of genetic information across generations for eukaryote species. The centromere is a specialized chromosomal region that is essential for mediating sister chromatid alignment and separation during mitosis. Centromere identity is epigenetically determined by nucleosome-containing centromere protein A (CENP-A). The CENP-A nucleosome provides the foundation for the association of the inner kinetochore and the assembly of the outer kinetochore in mitosis. Here we review centromere identity determination, inner kinetochore function and assembly, and outer kinetochore function and assembly. In particular, we focus on the recent advances in the structure-activity relationship of the constitutive centromere-associated network (CCAN). CCAN structure information sheds new light on our understanding of centromere and kinetochore functions and dynamic organization.
Cryopreservation of oocytes: history, achievements and future
Shiyu Zhao, Gang Zhao
2023, 53(9): 0902. doi: 10.52396/JUSTC-2023-0072
Abstract:
There have been increasing requirements for women’s fertility preservation due to oncological and nononcological reasons in recent years, and meeting these demands will be a hot topic in the coming years. Oocyte cryopreservation is a workable option for preserving women’s fertility, and great advances have already been made and much progress has been made in mammalian gene banking and human oocyte banks. In this paper, we systematically introduce the history of oocyte cryopreservation and vitrification technology and highlight the vitrification carrier. Furthermore, we summarize the fundamentals of oocyte vitrification and discuss the effects of vitrification on oocyte quality. Strategies to improve the effect of oocyte cryopreservation are also proposed. At the end of this review, we conclude oocyte cryopreservation and outline future perspectives. There have been increasing requirements for women’s fertility preservation due to oncological and nononcological reasons in recent years, and meeting these demands will be a hot topic in the coming years. Oocyte cryopreservation is a workable option for preserving women’s fertility, and great advances have already been made and much progress has been made in mammalian gene banking and human oocyte banks. In this paper, we systematically introduce the history of oocyte cryopreservation and vitrification technology and highlight the vitrification carrier. Furthermore, we summarize the fundamentals of oocyte vitrification and discuss the effects of vitrification on oocyte quality. Strategies to improve the effect of oocyte cryopreservation are also proposed. At the end of this review, we conclude oocyte cryopreservation and outline future perspectives.
Modulating miRNA binding sites within circRNA for enhanced translation efficiency
Kewei Zhang, Ge Shan, Liang Chen
2023, 53(9): 0904. doi: 10.52396/JUSTC-2023-0048
Abstract:
Circular RNAs (circRNAs) are covalently closed circular RNAs, and some of them preserve translation potency. However, modulation of circRNA translation efficiency and its applications need to be explored. In this study, RNAs containing the translation initiation element CVB3 IRES and the coding sequence of luciferase protein were transcribed and circularized in vitro by T7 RNA polymerase and an optimized permutated intron‒exon (PIE) splicing strategy. The circularized RNAs were then transfected and translated into active luciferase in the cultured cells. Insertion of miRNA binding sites at the flanking region of the luciferase coding sequence significantly reduced the translation efficiency of the circRNAs. Mutations of the miRNA binding sites in the firefly luciferase coding sequence led to increased translation efficiency of synthetic circRNAs in cells. We also proved that mutations of the binding sites of specific miRNAs also enhanced the translation efficiency of synthetic circRNAs. Further in vivo experiments via bioluminescence imaging showed that synonymous mutation of the miRNA binding sites promoted synthetic circRNA translation in nude mice. This study demonstrates that the modulation of miRNA binding sites affects the translation efficiency of synthetic circRNAs in vitro and in vivo, which could be used as versatile tools for future applications in clinical imaging. Circular RNAs (circRNAs) are covalently closed circular RNAs, and some of them preserve translation potency. However, modulation of circRNA translation efficiency and its applications need to be explored. In this study, RNAs containing the translation initiation element CVB3 IRES and the coding sequence of luciferase protein were transcribed and circularized in vitro by T7 RNA polymerase and an optimized permutated intron‒exon (PIE) splicing strategy. The circularized RNAs were then transfected and translated into active luciferase in the cultured cells. Insertion of miRNA binding sites at the flanking region of the luciferase coding sequence significantly reduced the translation efficiency of the circRNAs. Mutations of the miRNA binding sites in the firefly luciferase coding sequence led to increased translation efficiency of synthetic circRNAs in cells. We also proved that mutations of the binding sites of specific miRNAs also enhanced the translation efficiency of synthetic circRNAs. Further in vivo experiments via bioluminescence imaging showed that synonymous mutation of the miRNA binding sites promoted synthetic circRNA translation in nude mice. This study demonstrates that the modulation of miRNA binding sites affects the translation efficiency of synthetic circRNAs in vitro and in vivo, which could be used as versatile tools for future applications in clinical imaging.
An abnormal multidrug-resistant and hypervirulent Klebsiella pneumoniae clinical isolate without rmpA or rmpA2
Zhien He, Liwen Cao, Yuanyuan Dai, Huaiwei Lu, Baolin Sun, Yujie Li
2023, 53(9): 0905. doi: 10.52396/JUSTC-2023-0085
Abstract:
Klebsiella pneumoniae is a notorious opportunistic pathogen, especially hypervirulent K. pneumoniae (hvKp). Fortunately, most classical hvKp strains are antibiotic-susceptible. However, in recent years, reports of multidrug-resistant hvKp (MDR-hvKp) have increased dramatically, threatening the health and safety of people worldwide. Here, we report the discovery of MDR-hvKp without rmpA and rmpA2 in a 92-year-old patient with chronic obstructive pulmonary disease. The patient died on the eighth day of hospitalization. Phenotyping experiments and whole-genome sequencing of K. pneumoniae isolate 21072329 isolated from the patient’s sputum were performed. Moreover, 21072329 belongs to ST11-KL47 MDR-hvKp, which was highly lethal to Galleria mellonella. Meanwhile, 21072329 had a strong viscosity, and it was difficult to completely centrifuge it; 21072329 carried ESBL genes (blaCTX-M-65, blaSHV-158, and blaTEM-1) and a carbapenemase gene (blaKPC-2), and it was resistant to carbapenem antibiotics and third- and fourth-generation cephalosporins. Although 21072329 had the characteristics of hvKp, rmpA and rmpA2 could not be found in its genome; it also only carried a siderophore of yersiniabactin. This may indicate that other hypervirulence factors promote the formation of hvKp. MDR-hvKp has already brought an enormous burden to global medical care, and those carrying unknown hypervirulence factors are new threats, so urgent prevention and control with research are urgently needed. Klebsiella pneumoniae is a notorious opportunistic pathogen, especially hypervirulent K. pneumoniae (hvKp). Fortunately, most classical hvKp strains are antibiotic-susceptible. However, in recent years, reports of multidrug-resistant hvKp (MDR-hvKp) have increased dramatically, threatening the health and safety of people worldwide. Here, we report the discovery of MDR-hvKp without rmpA and rmpA2 in a 92-year-old patient with chronic obstructive pulmonary disease. The patient died on the eighth day of hospitalization. Phenotyping experiments and whole-genome sequencing of K. pneumoniae isolate 21072329 isolated from the patient’s sputum were performed. Moreover, 21072329 belongs to ST11-KL47 MDR-hvKp, which was highly lethal to Galleria mellonella. Meanwhile, 21072329 had a strong viscosity, and it was difficult to completely centrifuge it; 21072329 carried ESBL genes (blaCTX-M-65, blaSHV-158, and blaTEM-1) and a carbapenemase gene (blaKPC-2), and it was resistant to carbapenem antibiotics and third- and fourth-generation cephalosporins. Although 21072329 had the characteristics of hvKp, rmpA and rmpA2 could not be found in its genome; it also only carried a siderophore of yersiniabactin. This may indicate that other hypervirulence factors promote the formation of hvKp. MDR-hvKp has already brought an enormous burden to global medical care, and those carrying unknown hypervirulence factors are new threats, so urgent prevention and control with research are urgently needed.
Dynamics in the assembly of the 30S ribosomal subunit investigated by coarse-grained simulations
Xin Liu, Zhiyong Zhang
2023, 53(9): 0906. doi: 10.52396/JUSTC-2023-0064
Abstract:
The ribosome is a large biomolecular complex responsible for protein synthesis. In Escherichia coli (E. coli), a complete ribosome is composed of a 30S small subunit and a 50S large subunit. For approximately half a century, the 30S subunit has been a key model system for studying the in vitro assembly of the ribosome, and an assembly map has been proposed. However, structural details in the assembly of this protein‒RNA complex remain elusive. In this paper, we conducted a series of coarse-grained simulations following the order of the assembly map to investigate conformational dynamics during the assembly process of the 30S subunit. It has been found that the tertiary structure of naked 16S rRNA is very unstable, which is the case after binding of early-assembly proteins. The mid-assembly proteins can significantly restrict the mobility of the 16S rRNA and make the latter close to the native structure. The final binding of the late-assembly proteins would fully obtain the collective motion of the 16S rRNA. In particular, proteins S9 and S3 may have more important contributions to the assembly of the 30S subunit than other S proteins. Our strategy of coarse-grained simulations can be generally used to study assembly dynamics of large biomolecular complexes as long as the assembly map is available. The ribosome is a large biomolecular complex responsible for protein synthesis. In Escherichia coli (E. coli), a complete ribosome is composed of a 30S small subunit and a 50S large subunit. For approximately half a century, the 30S subunit has been a key model system for studying the in vitro assembly of the ribosome, and an assembly map has been proposed. However, structural details in the assembly of this protein‒RNA complex remain elusive. In this paper, we conducted a series of coarse-grained simulations following the order of the assembly map to investigate conformational dynamics during the assembly process of the 30S subunit. It has been found that the tertiary structure of naked 16S rRNA is very unstable, which is the case after binding of early-assembly proteins. The mid-assembly proteins can significantly restrict the mobility of the 16S rRNA and make the latter close to the native structure. The final binding of the late-assembly proteins would fully obtain the collective motion of the 16S rRNA. In particular, proteins S9 and S3 may have more important contributions to the assembly of the 30S subunit than other S proteins. Our strategy of coarse-grained simulations can be generally used to study assembly dynamics of large biomolecular complexes as long as the assembly map is available.
Recent progress on diaCEST MRI for tumor imaging
Qin Yu, Zian Yu, Lijiao Yang, Yue Yuan
2023, 53(6): 0601. doi: 10.52396/JUSTC-2023-0027
Abstract:
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an advanced imaging method that probes the chemical exchange between bulk water protons and exchangeable solute protons. This chemical exchange decreases the MR signal of water and reveals the distribution and concentration of certain endogenous biomolecules or extrogenous contrast agents in organisms with high sensitivity and spatial resolution. The CEST signal depends not only on the concentration of the CEST contrast agent and external magnetic field but also on the surrounding environments of the contrast agent, such as pH and temperature, thus enabling CEST MRI to monitor pH, temperature, metabolic level, and enzyme activity in vivo. In this review, we discuss the principle of CEST MRI and mainly summarize the recent progress of diamagnetic CEST (diaCEST) contrast agents on tumor imaging, diagnosis, and therapy effect evaluation. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an advanced imaging method that probes the chemical exchange between bulk water protons and exchangeable solute protons. This chemical exchange decreases the MR signal of water and reveals the distribution and concentration of certain endogenous biomolecules or extrogenous contrast agents in organisms with high sensitivity and spatial resolution. The CEST signal depends not only on the concentration of the CEST contrast agent and external magnetic field but also on the surrounding environments of the contrast agent, such as pH and temperature, thus enabling CEST MRI to monitor pH, temperature, metabolic level, and enzyme activity in vivo. In this review, we discuss the principle of CEST MRI and mainly summarize the recent progress of diamagnetic CEST (diaCEST) contrast agents on tumor imaging, diagnosis, and therapy effect evaluation.
Polymerized small molecular dyes providing nanoparticles with stable photosensitivity for eradicating cancer cells
Xu Chen, Feng Gao, Lihua Yang
2023, 53(6): 0607. doi: 10.52396/JUSTC-2023-0056
Abstract:
To make small molecular photosensitizer-based nanoparticles photostable, we polymerized such photosensitizers via emulsion polymerization, and the resulting nanoparticles exhibited sustained absorption of the excitation wavelength in the near-infrared region, generated stable photothermal and photodynamic effects upon repeated irradiation with an near-infrared laser, and efficiently eradicated cancerous cells even after prior irradiation exposure. To make small molecular photosensitizer-based nanoparticles photostable, we polymerized such photosensitizers via emulsion polymerization, and the resulting nanoparticles exhibited sustained absorption of the excitation wavelength in the near-infrared region, generated stable photothermal and photodynamic effects upon repeated irradiation with an near-infrared laser, and efficiently eradicated cancerous cells even after prior irradiation exposure.
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