Publications by authors named "Yan Guo"

1,852 Publications

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Development of a Bicistronic Yellow Fever Live Attenuated Vaccine with Reduced Neurovirulence and Viscerotropism.

Microbiol Spectr 2022 Aug 18:e0224622. Epub 2022 Aug 18.

Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.

The yellow fever (YF) live attenuated vaccine strain 17D (termed 17D) has been widely used for the prevention and control of YF disease. However, 17D retains significant neurovirulence and viscerotropism in mice, which is probably linked to the increased occurrences of serious adverse events following 17D vaccination. Thus, the development of an updated version of the YF vaccine with an improved safety profile is of high priority. Here, we generated a viable bicistronic YF virus (YFV) by incorporating the internal ribosome entry site (IRES) from virus into an infectious clone of YFV 17D. The resulting recombinant virus, 17D-IRES, exhibited similar replication efficiency to its parental virus (17D) in mammalian cell lines, while it was highly restricted in mosquito cells. Serial passage of 17D-IRES in BHK-21 cells showed good genetic stability. More importantly, in comparison with the parental 17D, 17D-IRES displayed significantly decreased mouse neurovirulence and viscerotropism in type I interferon (IFN)-signaling-deficient and immunocompetent mouse models. Interestingly, 17D-IRES showed enhanced sensitivity to type I IFN compared with 17D. Moreover, immunization with 17D-IRES provided solid protection for mice against a lethal challenge with YFV. These preclinical data support further development of 17D-IRES as an updated version for the approved YF vaccine. This IRES-based attenuation strategy could be also applied to the design of live attenuated vaccines against other mosquito-borne flaviviruses. Yellow fever (YF) continually spreads and causes epidemics around the world, posing a great threat to human health. The YF live attenuated vaccine 17D is considered the most efficient vaccine available and helps to successfully control disease epidemics. However, side effects may occur after vaccination, such as viscerotropic disease (YEL-AVD) and neurotropic adverse disease (YEL-AND). Thus, there is an urgent need for a safer YF vaccine. Here, an IRES strategy was employed, and a bicistronic YFV was successfully developed (named 17D-IRES). 17D-IRES showed effective replication and genetic stability and high attenuation . Importantly, 17D-IRES induced humoral and cellular immune responses and conferred full protection against lethal YFV challenge. Our study provides data suggesting that 17D-IRES, with its prominent advantages, could be a vaccine candidate against YF. Moreover, this IRES-based bicistronic technology platform represents a promising strategy for developing other live attenuated vaccines against emerging viruses.
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http://dx.doi.org/10.1128/spectrum.02246-22DOI Listing
August 2022

Blood routine reference value range should be adjusted according to regional and ethnic characteristics.

Front Public Health 2022 29;10:934101. Epub 2022 Jul 29.

Department of Respiratory, Qinghai Provincial People's Hospital, Xining, China.

Objective: To further understand the influence of regional and ethnic factors on blood routine indicators.

Methods: The routine blood test (RBT) results of 617 healthy men aged 18-45 years old of the Li, Tibet, and Han nationalities living in the city of Sanya, Hainan Province (200 m), the city of Xining, Qinghai Province (2,300 m), and Maduo County of Qinghai Province (4,300 m) for a long time were studied. Eight indexes, such as the red blood cell (RBC), hemoglobin (Hb), and platelet (PLT) counts, were compared and analyzed.

Results: With an increase in altitude, the RBT index values and change trends of the different ethnic groups were different. When the altitude increased by 2,000 m, the RBC and Hb increased by 6.6 and 8.1%, respectively, and the PLT decreased by 16.8%. However, the RBC, Hb, and PLT of the Tibetan subjects decreased by 7.4, 5.1, and 3.0%, respectively. In the same region, there were also significant differences in the RBT index values among the ethnic groups. The RBC increased, Hb decreased, and PLT did not change in the Li nationality in Sanya compared with the Han nationality. The RBC, Hb, and PLT of Tibetans in the Xining area were significantly higher than those of the Han population. Referring to the current RBT reference value range in China, the abnormal rates of the various RBT index values of the enrolled population were high. By utilizing Hb as an example, 27.7% of the Li nationality in Sanya was low, 67.0% of the Tibetan nationality in Xining was high, and 89.4% of the Maduo Han nationality was high. The PLT was lower in the Sanya Li nationality (13.8%) and the Maduo Han nationality (88.3%).

Conclusion: Regional and ethnic factors have a significant impact on the RBT, and the current range of normal values of the RBT in China needs to be revised and adjusted.
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http://dx.doi.org/10.3389/fpubh.2022.934101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372343PMC
August 2022

The correlation between transcription factor 7-like 2 gene polymorphisms and susceptibility of gestational diabetes mellitus in the population of central China: A case-control study.

Front Endocrinol (Lausanne) 2022 29;13:916590. Epub 2022 Jul 29.

School of Public Health, Wuhan University of Science and Technology, Wuhan, China.

Objective: To investigate the correlation between transcription factor 7-like 2 (TCF7L2) gene polymorphisms and gestational diabetes mellitus (GDM) risk in the central Chinese population.

Methods: This case-control study examined the association of seven gene single-nucleotide polymorphisms (SNPs) (rs11196218, rs4506565, rs7895340, rs7901695, rs11196205, rs12243326, and rs290487) with GDM risk in the central Chinese population (843 GDM and 877 controls). The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including -test, ANOVA, chi-square test, Fisher's exact test, and logistic regression were performed.

Results: Differences in age, pre-pregnant body mass index (BMI), and family history of type 2 diabetes mellitus (T2DM) between the case and control groups were significant ( < 0.05). Compared with the wild-type genotype, pregnant women with genotypes of rs4506565-AT ( = 1.89, 95%: 1.18-3.02), rs7895340 GA ( = 1.93, 95%: 1.06-3.54), rs7901695-TC ( = 1.79, 95%: 1.11-2.88), and rs11196205-GC ( = 2.15, 95%: 1.16-3.98) had a significantly higher risk of GDM, adjusted by age, pre-pregnant BMI, and family history of T2DM. Functional annotation showed that all these four SNPs fell in the functional elements of human pancreatic islets. Further cumulative effects analysis concluded that when participants carried all these four risk genotypes, the risk of GDM was 3.51 times ( = 3.51, 95%: 1.38-8.90) than that of those without any risk genotypes.

Conclusions: The findings of this study suggested that rs4506565, rs7895340, rs7901695, and rs11196205 were the genetic susceptibility SNPs of GDM in the central Chinese population. Further studies are needed to validate our findings and clarify the underlying mechanisms.
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http://dx.doi.org/10.3389/fendo.2022.916590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372265PMC
August 2022

Clinical Efficacy and Safety of Different Dental Prosthetic Membranes in Guided Bone Regeneration during Dental Implants: A Meta-Analysis.

Comput Intell Neurosci 2022 31;2022:3245014. Epub 2022 Jul 31.

Department of Stomatology, The 940th Hospital of Joint Logistic Support Force of PLA, Lanzhou 730050, China.

. To evaluate clinical efficacy and safety of absorbable and non-absorbable dental restorative membranes in guided bone regeneration (GBR). Articles concerning absorbable and non-absorbable prosthetic membrane-related studies of GBR were screened from multiple databases. In the end, 526 postoperative patients who met eligibility criteria were screened for the study from eight trials. The results showed that the repair success rate of the experimental group (absorbable dental restorative membrane) was higher than that of the control group (non-absorbable dental restorative membrane) (RR = 1.18, 95% CI [1.11,1.26], and the total physical therapy effect was  < 0.0001,  = 0%), and the height of bone graft in the experimental group was higher than that in the control group (MD = 0.67, 95% CI [0.11, 1.23]). The thickness of bone graft in the experimental group was higher than that in the control group (MD = 0.43, 95% CI [0.30,0.56],  < 0.00001,  = 61%), and the adverse events in the experimental group were less than those in the control group (RR = 0.31, 95% CI [0.18, 0.51],  < 0.00001,  = 13%). Absorbable prosthetic membrane is superior to non-absorbable prosthetic membrane in clinical efficacy and safety.
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http://dx.doi.org/10.1155/2022/3245014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357784PMC
August 2022

Effectively Identifying Compound-Protein Interaction using Graph Neural Representation.

IEEE/ACM Trans Comput Biol Bioinform 2022 Aug 11;PP. Epub 2022 Aug 11.

Effectively identifying compound-protein interactions (CPIs) is crucial for new drug design, which is an important step in silico drug discovery. Current machine learning methods for CPI prediction mainly use one-demensional (1D) compound/protein strings and/or the specific descriptors. However, they often ignore the fact that molecules are essentially modeled by the molecular graph. We observe that in real-world scenarios, the topological structure information of the molecular graph usually provides an overview of how the atoms are connected, and the local chemical context reveals the functionality of the protein sequence in CPI. These two types of information are complementary to each other and they are both significant for modeling compound-protein pairs. Motivated by this, we propose an end-to-end deep learning framework named GraphCPI, which captures the structural information of compounds and leverages the chemical context of protein sequences for solving the CPI prediction task. Our framework can integrate any popular graph neural networks for learning compounds, and it combines with a convolutional neural network for embedding sequences. To compare our method with classic and state-of-the-art deep learning methods, we conduct extensive experiments based on several widely-used CPI datasets. The experimental results show the feasibility and competitiveness of our proposed method.
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http://dx.doi.org/10.1109/TCBB.2022.3198003DOI Listing
August 2022

Metal Ions as the Third Component Coordinate with the Guest to Stereoscopically Enhance the Phosphorescence Properties of Doped Materials.

J Phys Chem Lett 2022 Aug 11;13(32):7607-7617. Epub 2022 Aug 11.

College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P.R. China.

The construction of multicomponent doped systems is an important direction for the development of phosphorescence materials. Herein, benzophenone is selected as the host, phenylquinoline isomers are designed as guests, and seven metal ions are selected as the third component (Al, Cu, Zn, Ga, Ag, Cd, and In) to construct the three-component doped system. Ag and Cd can considerably increase the emission intensity up to 38 times, and the highest phosphorescence quantum efficiency reaches 70%. Al, Ga, and In can prolong the emission wavelength, and the phosphorescence wavelength can be red-shifted up to 60 nm. Cu, Ga, and In can extend the phosphorescence lifetime by a maximum of 3.6 times. A series of experiments demonstrated that the coordination of metals and guests is the key to improve the phosphorescence properties. This work presents a simple and effective strategy to enhance the phosphorescence properties of doped materials.
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http://dx.doi.org/10.1021/acs.jpclett.2c02057DOI Listing
August 2022

Transcription-coupled donor DNA expression increases homologous recombination for efficient genome editing.

Nucleic Acids Res 2022 Aug 5. Epub 2022 Aug 5.

Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Genomes can be edited by homologous recombination stimulated by CRISPR/Cas9 [clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated peptide 9]-induced DNA double-strand breaks. However, this approach is inefficient for inserting or deleting long fragments in mammalian cells. Here, we describe a simple genome-editing method, termed transcription-coupled Cas9-mediated editing (TEd), that can achieve higher efficiencies than canonical Cas9-mediated editing (CEd) in deleting genomic fragments, inserting/replacing large DNA fragments and introducing point mutations into mammalian cell lines. We also found that the transcription on DNA templates is crucial for the promotion of homology-directed repair, and that tethering transcripts from TEd donors to targeted sites further improves editing efficiency. The superior efficiency of TEd for the insertion and deletion of long DNA fragments expands the applications of CRISPR for editing mammalian genomes.
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http://dx.doi.org/10.1093/nar/gkac676DOI Listing
August 2022

Deep-Learning-Based Ultrasound Sound-Speed Tomography Reconstruction with Tikhonov Pseudo-Inverse Priori.

Ultrasound Med Biol 2022 Jul 31. Epub 2022 Jul 31.

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address:

Ultrasound sound-speed tomography (USST) is a promising technology for breast imaging and breast cancer detection. Its reconstruction is a complex non-linear mapping from the projection data to the sound-speed image (SSI). The traditional reconstruction methods include mainly the ray-based methods and the waveform-based methods. The ray-based methods with linear approximation have low computational cost but low reconstruction quality; the full wave-based methods with the complex non-linear model have high quality but high cost. To achieve both high quality and low cost, we introduced traditional linear approximation as prior knowledge into a deep neural network and treated the complex non-linear mapping of USST reconstruction as a combination of linear mapping and non-linear mapping. In the proposed method, the linear mapping was seamlessly implemented with a fully connected layer and initialized using the Tikhonov pseudo-inverse matrix. The non-linear mapping was implemented using a U-shape Net (U-Net). Furthermore, we proposed the Tikhonov U-shape net (TU-Net), in which the linear mapping was done before the non-linear mapping, and the U-shape Tikhonov net (UT-Net), in which the non-linear mapping was done before the linear mapping. Moreover, we conducted simulations and experiments for evaluation. In the numerical simulation, the root-mean-squared error was 6.49 and 4.29 m/s for the UT-Net and TU-Net, the peak signal-to-noise ratio was 49.01 and 52.90 dB, the structural similarity was 0.9436 and 0.9761 and the reconstruction time was 10.8 and 11.3 ms, respectively. In this study, the SSIs obtained with the proposed methods exhibited high sound-speed accuracy. Both the UT-Net and the TU-Net achieved high quality and low computational cost.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2022.05.033DOI Listing
July 2022

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study.

Lancet Reg Health West Pac 2022 Sep 26;26:100520. Epub 2022 Jul 26.

Shanghai Municipal Center for Disease Control and Prevention, No. 1380 Zhongshan West Street, Changning District, Shanghai City 200051, China.

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China.

Methods: In 2020-2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death).

Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions.

Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms.

Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].
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http://dx.doi.org/10.1016/j.lanwpc.2022.100520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335373PMC
September 2022

Lineage-specific rearrangement of chromatin loops and epigenomic features during adipocytes and osteoblasts commitment.

Cell Death Differ 2022 Jul 29. Epub 2022 Jul 29.

Biomedical Informatics & Genomics Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, P. R. China.

Human mesenchymal stem cells (hMSCs) can be differentiated into adipocytes and osteoblasts. The processes are driven by the rewiring of chromatin architectures and transcriptomic/epigenomic changes. Here, we induced hMSCs to adipogenic and osteogenic differentiation, and performed 2 kb resolution Hi-C experiments for chromatin loops detection. We also generated matched RNA-seq, ChIP-seq and ATAC-seq data for integrative analysis. After comprehensively comparing adipogenesis and osteogenesis, we quantitatively identified lineage-specific loops and screened out lineage-specific enhancers and open chromatin. We reveal that lineage-specific loops can activate gene expression and facilitate cell commitment through combining enhancers and accessible chromatin in a lineage-specific manner. We finally proposed loop-mediated regulatory networks and identified the controlling factors for adipocytes and osteoblasts determination. Functional experiments validated the lineage-specific regulation networks towards IRS2 and RUNX2 that are associated with adipogenesis and osteogenesis, respectively. These results are expected to help better understand the chromatin conformation determinants of hMSCs fate commitment.
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http://dx.doi.org/10.1038/s41418-022-01035-7DOI Listing
July 2022

The Investigation of HBV Pre-S/S Gene Mutations in Occult HBV Infected Blood Donors with anti-HBs Positive.

Can J Infect Dis Med Microbiol 2022 19;2022:1874435. Epub 2022 Jul 19.

Clinical Laboratory, Shaanxi Blood Center, Zhuque Street No.407, Yanta District, Xi'an, Shaanxi 710061, China.

Introduction: The coexistence of hepatitis B virus (HBV) and hepatitis B surface antibodies (anti-HBs) in occult hepatitis B virus infection (OBI) is a contradictory phenomenon, and the underlying mechanism is not fully understood. The characteristics of pre-S/S mutations in OBI genotypes B and C (OBI and OBI) in the presence or absence of anti-HBs were analyzed extensively in this study. . The amino acid substitutions of envelope proteins of 21 OBI strains, including 4 HBs (+) OBI, 6 HBs (-) OBI, 6 HBs (+) OBIc, and 5 HBs (-) OBI samples, were analyzed and fully compared among groups of HBV genotypes and the presence of anti-HBs.

Results: The mutation rates in pre-S1, pre-S2, and S proteins of OBI were significantly higher than wild-type HBV (wt-HBV) genotype C strains, but only the mutation rate of S protein in OBI was significantly higher compared to wild-type HBV genotype B. The mutation rates in S protein of anti-HBs (-) OBI were higher than anti-HBs(+) OBI samples (4.40% vs. 2.43% in genotype B, > 0.05; 6.81% vs. 3.47% in genotype C, < 0.05). For these high-frequency substitutions in the pre-S/S region, the mutations sN40S and sK122R were found in 27.3% and 45.5% of anti-HBs (-) OBI strains, respectively. 7 substitutions were uniquely found in OBI strains and 9 substitutions were commonly detected in OBI and OBI strains.

Conclusions: These results suggested that the mutations might occur randomly and were not selected by antibody pressure.
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http://dx.doi.org/10.1155/2022/1874435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325327PMC
July 2022

Influencing Factors of Mental Health Status of Dentists Under COVID-19 Epidemic.

Front Psychiatry 2022 11;13:933514. Epub 2022 Jul 11.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.

Objective: To investigate dentists' psychological status and influencing factors in Shaanxi Province during the COVID-19 epidemic and assess their perceived wellness.

Methods: The study was conducted among dentists from Shaanxi Province in China. The basic information was collected through the network questionnaire star platform. Depression, Anxiety, and Stress Scales (DASS-42) and Perceived Wellness Survey (PWS) were used to assess subjects' psychological status and perceived wellness. Univariate linear regression analysis and multivariate analysis were performed on the influencing factors of depression, anxiety, and stress, and -test and analysis of variance were used to analyze the perceived wellness results.

Results: The results demonstrated that 33.2% of the surveyed dentists were in a state of depression, 37.1% were anxious, and 34.4% reported stress among 256 subjects. Linear Regression analysis results showed that: "years of working," "the impact of COVID-19 on their life, work, and sleep," "worrying about occupational exposure/virus infection," "lacking the awareness of prevention and control measures," "overtime work during the epidemic," "worrying about participating in the supporting work," and "continuous exhaustion from work" were significant contributors to depression, anxiety, and stress status. In addition, the results of PWS found that each dimension of PWS was correlated with depression, anxiety, and stress state, which indicates the individual's physical and mental health state was associated with multiple factors.

Conclusion: COVID-19 has significantly impacted dentists' mental health in Shaanxi Province. With these findings, we aim to educate and promote targeted interventions that can be utilized to improve dentists' mental health by analyzing the influencing factors.
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http://dx.doi.org/10.3389/fpsyt.2022.933514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309335PMC
July 2022

Pip Blocks Zika Virus Transovarial Transmission in .

Microbiol Spectr 2022 Jul 27:e0263321. Epub 2022 Jul 27.

Key Laboratory of Tropical Disease Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.

is being developed as a biological tool to suppress mosquito populations and/or interfere with their transmitted viruses. Adult males with an artificial infection have been released, successfully yielding population suppression in multiple field trials. The main characteristic of the artificial -infected mosquitoes used in the suppression program is the lower vector competence than that in native infected/uninfected mosquitoes in horizontal and vertical transmission. Our previous studies have demonstrated that the Aedes albopictus HC line infected with a trio of strains exhibited almost complete blockade of dengue virus (DENV) and Zika virus (ZIKV) in horizontal and vertical transmission. However, the extent to which inhibits virus transovarial transmission is unknown since no studies have been performed to determine whether protects ovarian cells against viral infection. Here, we employed ovarian cells of the . GUA (a wild-type mosquito line superinfected with two native strains, AlbA and AlbB), HC, and GT lines (tetracycline-cured, -uninfected mosquitoes), which exhibit key traits, and compared them to better understand how inhibits ZIKV transovarial transmission. Our results showed that the infection rate of adult GT progeny was significantly higher than that of GUA progeny during the first and second gonotrophic cycles. In contrast, the infection rates of adult GT and GUA progeny were not significantly different during the third gonotrophic cycle. All examined adult HC progeny from three gonotrophic cycles were negative for ZIKV infection. A strong negative linear correlation existed between density and ZIKV load in the ovaries of mosquitoes. Although there is no obvious coexistence area in the ovaries for and ZIKV, host immune responses may play a role in blocking ZIKV expansion and maintenance in the ovaries of . These results will aid in understanding -ZIKV interactions in mosquitoes. Area-wide application of to suppress mosquito populations and their transmitted viruses has achieved success in multiple countries. However, the mass release of -infected male mosquitoes involves a potential risk of accidentally releasing fertile females. In this study, we employed ovarian cells of the GUA, HC, and GT lines, which exhibit key traits, and compared them to better understand how inhibits ZIKV transovarial transmission. Our results showed an almost complete blockade of ZIKV transmission in HC female mosquitoes. in natively infected GUA mosquitoes negative affected ZIKV, and this interference was shown by slightly lower loads than those in HC mosquitoes. Overall, our work helps show how blocks ZIKV expansion and maintenance in the ovaries of and aids in understanding -ZIKV interactions in mosquitoes.
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http://dx.doi.org/10.1128/spectrum.02633-21DOI Listing
July 2022

Protection against Hypoxia-Reoxygenation Injury of Hippocampal Neurons by HS via Promoting Phosphorylation of ROCK at Tyr722 in Rat Model.

Molecules 2022 Jul 18;27(14). Epub 2022 Jul 18.

Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.

The RhoA-ROCK signaling pathway is associated with the protective effects of hydrogen sulfide (HS) against cerebral ischemia. HS protects rat hippocampal neurons (RHNs) against hypoxia-reoxygenation (H/R) injury by promoting phosphorylation of RhoA at Ser188. However, effect of HS on the phosphorylation of ROCK-related sites is unclear. The present study was designed to investigate whether HS can play a role in the phosphorylation of ROCK at Tyr722, and explore whether this role mediates the protective effect of H/R injury in RHNs. Prokaryotic recombinant plasmids ROCK-pGEX-6P-1 and ROCK-pGEX-6P-1 were constructed and transfected into in vitro, and the expressed protein, GST-ROCK and GST-ROCK were used for phosphorylation assay in vitro. Eukaryotic recombinant plasmids ROCK-pEGFP-N1 and ROCK-pEGFP-N1 as well as empty plasmid were transfected into the RHNs. Western blot assay and whole-cell patch-clamp technique were used to detect phosphorylation of ROCK at Tyr722 and BK channel current in the RHNs, respectively. Cell viability, leakages of intracellular enzymes lactate dehydrogenase (LDH), and nerve-specific enolase (NSE) were measured. The H/R injury was indicated by decrease of cell viability and leakages of intracellular LDH and NSE. The results of Western blot have shown that NaHS, a HS donor, significantly promoted phosphorylation of GST-ROCK at Tyr722, while no phosphorylation of GST-ROCK was detected. The phosphorylation of ROCK promoted by NaHS was also observed in RHNs. NaHS induced more potent effects on protection against H/R injury, phosphorylation of ROCK at Tyr722, inhibition of ROCK activity, as well as increase of the BK current in the ROCK-pEGFP-N1-transfected RHNs. Our results revealed that HS protects the RHNs from H/R injury through promoting phosphorylation of ROCK at Tyr722 to inhibit ROCK activity and potentially by opening channel currents.
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http://dx.doi.org/10.3390/molecules27144567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319530PMC
July 2022

Predicting the 2-Year Risk of Progression from Prediabetes to Diabetes Using Machine Learning among Chinese Elderly Adults.

J Pers Med 2022 Jun 27;12(7). Epub 2022 Jun 27.

Wuhan Center for Disease Control and Prevention, Wuhan 430015, China.

Identifying people with a high risk of developing diabetes among those with prediabetes may facilitate the implementation of a targeted lifestyle and pharmacological interventions. We aimed to establish machine learning models based on demographic and clinical characteristics to predict the risk of incident diabetes. We used data from the free medical examination service project for elderly people who were 65 years or older to develop logistic regression (LR), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost) machine learning models for the follow-up results of 2019 and 2020 and performed internal validation. The receiver operating characteristic (ROC), sensitivity, specificity, accuracy, and F1 score were used to select the model with better performance. The average annual progression rate to diabetes in prediabetic elderly people was 14.21%. Each model was trained using eight features and one outcome variable from 9607 prediabetic individuals, and the performance of the models was assessed in 2402 prediabetes patients. The predictive ability of four models in the first year was better than in the second year. The XGBoost model performed relatively efficiently (ROC: 0.6742 for 2019 and 0.6707 for 2020). We established and compared four machine learning models to predict the risk of progression from prediabetes to diabetes. Although there was little difference in the performance of the four models, the XGBoost model had a relatively good ROC value, which might perform well in future exploration in this field.
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http://dx.doi.org/10.3390/jpm12071055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324396PMC
June 2022

Drug-Target Network Study Reveals the Core Target-Protein Interactions of Various COVID-19 Treatments.

Genes (Basel) 2022 Jul 6;13(7). Epub 2022 Jul 6.

Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

The coronavirus disease 2019 (COVID-19) pandemic has caused a dramatic loss of human life and devastated the worldwide economy. Numerous efforts have been made to mitigate COVID-19 symptoms and reduce the death rate. We conducted literature mining of more than 250 thousand published works and curated the 174 most widely used COVID-19 medications. Overlaid with the human protein-protein interaction (PPI) network, we used Steiner tree analysis to extract a core subnetwork that grew from the pharmacological targets of ten credible drugs ascertained by the CTD database. The resultant core subnetwork consisted of 34 interconnected genes, which were associated with 36 drugs. Immune cell membrane receptors, the downstream cellular signaling cascade, and severe COVID-19 symptom risk were significantly enriched for the core subnetwork genes. The lung mast cell was most enriched for the target genes among 1355 human tissue-cell types. Human bronchoalveolar lavage fluid COVID-19 single-cell RNA-Seq data highlighted the fact that T cells and macrophages have the most overlapping genes from the core subnetwork. Overall, we constructed an actionable human target-protein module that mainly involved anti-inflammatory/antiviral entry functions and highly overlapped with COVID-19-severity-related genes. Our findings could serve as a knowledge base for guiding drug discovery or drug repurposing to confront the fast-evolving SARS-CoV-2 virus and other severe infectious diseases.
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http://dx.doi.org/10.3390/genes13071210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316565PMC
July 2022

High Prevalence and Overexpression of Fosfomycin-Resistant Gene X in From China.

Front Microbiol 2022 8;13:900185. Epub 2022 Jul 8.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

i are one of the main causes of gastrointestinal tract infections in the healthcare system and can develop resistance to fosfomycin through plasmid or chromosomally encoded fosfomycin resistance genes. To investigate the mechanisms of fosfomycin resistance, a total of 4,414 clinical isolates of non-replicated clinical enterococci collected from 62 hospitals in 26 provinces or cities in China were tested. Antibiotic susceptibility testing, detection of fosfomycin resistance genes, and cloning of the X gene were done. The PFGE, MLST, qRT-PCR, and next genome sequencing were carried out. The results revealed that the fosfomycin-resistant rate of enterococci was 3.5% (153/4,414), and the major resistance mechanism was X (101/153) and B (52/153) genes. The X gene could increase 4- fold fosfomycin MIC in BM4105RF transformants, and the results of PFGE showed the 101 carrying X were grouped into 48 pulse types. The multilocus sequence typing identified ST555 as the vast majority of STs, mostly distributed in Shanghai, China. Furthermore, the X gene expression was strongly related to the fosfomycin-resistant levels of . The present study was the first to describe the high prevalence presence of the X gene in from China.
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http://dx.doi.org/10.3389/fmicb.2022.900185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304900PMC
July 2022

First Report of , , and Carrying Showing High-Level Resistance to Carbapenems.

Front Microbiol 2022 7;13:916304. Epub 2022 Jul 7.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

The prevalence of carbapenem-resistant is increasing. Although carbapenemase production is the main resistance mechanism of to carbapenems, there are still some reports of non-carbapenemase-producing showing high-level resistance to carbapenems. In this study, we had also isolated a carbapenemase-negative carbapenem-resistant L204 from a patient with an asymptomatic urinary tract infection. Species identification was performed using MALDI-TOF MS, and carbapenemase-encoding genes were detected using both NG-test carba-5 and whole-genome sequencing. Antimicrobial susceptibility testing was performed by the broth microdilution method according to CLSI guidance. The results of antimicrobial susceptibility testing indicated that L204 was resistant to meropenem (MIC = 16 mg/L) and imipenem (MIC = 4 mg/L), but susceptible to ceftazidime-avibactam (MIC = 8 mg/L). Through whole-genome sequencing, several resistance genes had been identified, including , , , , , , , , , and . The efflux pump inhibition testing showed that the efflux pump was not involved in the resistance mechanism to carbapenems. The result of the conjugation experiment indicated that the plasmid with and was transferrable. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that L204 only contained outer membrane porin OmpK35.
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http://dx.doi.org/10.3389/fmicb.2022.916304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301006PMC
July 2022

Activity of New β-Lactam-β-Lactamase Inhibitor Combinations and Comparators against Clinical Isolates of Gram-Negative Bacilli: Results from the China Antimicrobial Surveillance Network (CHINET) in 2019.

Microbiol Spectr 2022 Jul 12:e0185422. Epub 2022 Jul 12.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

Novel β-lactam-β-lactamase inhibitor combinations (BLBLIs) are in clinical development for the treatment of infections caused by carbapenem-resistant and difficult-to-treat resistant (DTR) (defined as resistance to all tested β-lactams and fluoroquinolones) Gram-negative bacilli. This study evaluated the activities of cefepime-zidebactam, ceftazidime-avibactam, cefepime-tazobactam, ceftolozane-tazobactam, and other comparators against 4,042 nonduplicate Gram-negative clinical isolates collected from different regions of China (46 hospitals) in 2019. Based on the pharmacokinetic-pharmacodynamic (PK-PD) breakpoints, cefepime-zidebactam inhibited 98.5% of and 98.9% of Pseudomonas aeruginosa isolates, respectively. Against carbapenem-resistant and difficult-to-treat resistant Gram-negative bacilli, cefepime-zidebactam demonstrated better activity against (96% and 97.2%, respectively) and P. aeruginosa (98.2% and 96.9%, respectively). Among the 379 carbapenem-resistant isolates, the most common carbapenemase genes detected were (64.1%) and (30.9%). Cefepime-zidebactam showed an MIC of ≤2 mg/L for 98.8% of -positive isolates and 89.7% of -positive isolates. Ceftazidime-avibactam also showed efficient activity against (93.6%) and P. aeruginosa (87.7%). Ceftazidime-avibactam was active against 97.5% of -positive isolates and 100% of -positive isolates. Cefepime-zidebactam inhibited 97.3% of Acinetobacter baumannii isolates with an MIC of 16/32 mg/L. Our study systematically evaluated the activities of these new BLBLIs against a variety of Gram-negative bacilli, provided preclinical data for the approval of these BLBLIs in China, and supported cefepime-zidebactam and ceftazidime-avibactam as potential efficient therapies for infections caused by carbapenem-resistant (CRE), carbapenem-resistant P. aeruginosa (CRPA), and DTR isolates. , Pseudomonas aeruginosa, and Acinetobacter baumannii are the most common Gram-negative bacilli to cause nosocomial infections throughout the world. Due to their large public health and societal implications, carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and carbapenem-resistant and third-generation-cephalosporin-resistant were regarded by the World Health Organization (WHO) as a global priority for investment in new drugs in 2017. The present study showed the potent activity of these novel BLBLIs and other comparators against Gram-negative bacillus isolates, including carbapenem-resistant or difficult-to-treat resistant phenotypes. Polymyxins, tigecycline, and ceftazidime-avibactam (except for -positive isolates) were available for the treatment of infections caused by CRE isolates. Currently, cefepime-zidebactam and other BLBLIs have not yet been approved for use in China. Here, our study aimed to evaluate the activities of BLBLIs against Gram-negative bacillus isolates, especially CRE, before clinical use.
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http://dx.doi.org/10.1128/spectrum.01854-22DOI Listing
July 2022

Genome Sequence of Acinetobacter baumannii Strain SHOU-Ab01, Isolated from Chinese Giant Salamander (Andrias davidianus) Liver.

Microbiol Resour Announc 2022 Aug 12;11(8):e0050322. Epub 2022 Jul 12.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.

This report describes the complete genome sequence of Acinetobacter baumannii strain SHOU-Ab01, which was isolated from the liver of a Chinese giant salamander (Andrias davidianus). SHOU-Ab01 belonged to sequence type 40 (ST40), and its genome contained a circular chromosome (size, 3,891,862 bp) and two circular plasmids (sizes, 8,571 bp and 5,870 bp).
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http://dx.doi.org/10.1128/mra.00503-22DOI Listing
August 2022

Is It Necessary to Remove the Implants After Fixation of Thoracolumbar and Lumbar Burst Fractures Without Fusion? A Retrospective Cohort Study of Elderly Patients.

Front Surg 2022 4;9:921678. Epub 2022 Jul 4.

Department of Orthopedics, Peking University Third Hospital, Beijing, China.

Objective: Fractures of the thoracolumbar spine are the most common fractures of the spinal column. This retrospective cohort study aimed to determine whether it is necessary to remove implants of patients aged over 65 years after the fixation of thoracolumbar and lumbar burst fractures without fusion.

Methods: This retrospective cohort study included 107 consecutive patients aged ≥65 years without neurological deficits, who underwent non-fusion short posterior segmental fixation for thoracolumbar or lumbar burst fractures. Outcome measures included the visual analog score (VAS), Oswestry Disability Index (ODI), residual symptoms, complications, and imaging parameters. Patients were divided into groups A (underwent implant removal) and B (implant retention) and were examined clinically at 1, 3, 6, and 12 months postoperatively and annually thereafter, with a final follow-up at 48.5 months.

Results: Overall, 96 patients with a mean age of 69.4 (range, 65-77) years were analyzed. At the latest follow-up, no significant differences were observed in functional outcomes and radiological parameters between both groups, except in the local motion range (LMR) ( = 0.006). Similarly, between preimplant removal and the latest follow-up in group A, significant differences were found only in LMR ( < 0.001). Two patients experienced screw breakage without clinical symptoms. Significant differences were only found in operation time, blood loss, ODI, and fracture type between minimally invasive group and open group.

Conclusions: Similar radiological and functional outcomes were observed in elderly patients, regardless of implant removal. Implant removal may not be necessary after weighing the risks and benefits for elderly patients. Patients should be informed about the possibility of implant breakage and accelerating degeneration of adjacent segments in advance.
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http://dx.doi.org/10.3389/fsurg.2022.921678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289234PMC
July 2022

Transcriptome analysis of mouse male germline stem cells reveals characteristics of mature spermatogonial stem cells.

Yi Chuan 2022 Jul;44(7):591-608

Center for Cell Lineage and Development ,Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

Spermatogonial stem cells (SSCs) are adult stem cells in the testis of male animals and have the ability in self-renewal and differentiation. SSCs are derived from primordial germ cells (PGCs) that are mitotically arrested in the embryo before birth. Following the birth of the animal, PGCs resume mitosis and migrate from the centre of the seminiferous tubules to the basement membrane. The descendent of PGCs (also called gonocytes) establish stable SSC colonies in about a week postnatally in order to support the life-long spermatogenesis. Whether SSCs at different developmental stages differ in their molecular and cellular characteristics is currently unclear. In the presented study, we conducted bioinformatics analyses using transcriptomics data established previously in the laboratory on OCT4 (encoded by the pluripotent gene Pou5f1) expressing SSCs from the neonatal (3 days-post-partum, 3-dpp), juvenile (7-dpp) and adult (2~3-month) mice, including screen of differentially expressed genes (DEGs), protein-protein interaction (PPI) network analysis of DEGs and clustering of sub-networks from PPI. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were also performed on clustered sub-networks of the PPI. In addition, all genes were analyzed using GSEA (gene set enrichment analysis) based on GO, KEGG and HALLMARK gene sets. The results showed that SSCs have a large number of DEGs among OCT4-positive SSCs from neonatal, juvenile and adult mice. The distinguishable biological functions encoded by these DEGs include biosynthesis and energy metabolism, immune response, cell junction and expression of migration and cell differentiation-related genes. Significant changes in the cell membrane composition of OCT4-positive SSCs may not only cause hypersensitive immune reactions but also affect the cell-cell contact and responses to secreted cytokines in the extracellular environment. The results also suggest that OCT4-positive SSCs may shift metabolic state from oxidative phosphorylation to glycolysis and significantly reduce the transcription of genes related to ribosome formation during aging. These results provide new clues for future research on the regulatory mechanisms of male germline stem cell development, growth and aging.
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http://dx.doi.org/10.16288/j.yczz.22-047DOI Listing
July 2022

Implications of the COVID-19 pandemic for urban informal housing and planning interventions: Evidence from Singapore.

Habitat Int 2022 Sep 14;127:102627. Epub 2022 Jul 14.

School of Urban Design, Wuhan University, Wuhan, China.

The outbreak of the COVID-19 pandemic revealed the crucial role of social distancing and hygiene practices in reducing virus transmission and thus revealed the high risk of infection in urban informal housing. Through an empirical study of Singapore's infectious situation and antiepidemic measures, this paper shows that the number of infected migrant workers living in dormitories was three hundred times greater than the number of infected local urban residents, not only because of the migrants' 'vulnerable' position but also because their living conditions fostered widespread transmission of the virus. The dwelling conditions of migrant dormitories, such as overcrowded living spaces, widely shared sanitation facilities, and poor hygiene practices, present great challenges to standard prevention strategies and control measures. Adverse health impacts resulting from the lockdown of dormitories during the COVID-19 pandemic suggest the importance of planning intervention in the dwelling conditions of informal housing, and indicate a need for the governments' active reforms of building codes and health care systems to promote the health of disadvantaged groups and then create more inclusive and healthy cities for all the society.
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http://dx.doi.org/10.1016/j.habitatint.2022.102627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279302PMC
September 2022

Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression.

Nat Hum Behav 2022 Jul 18. Epub 2022 Jul 18.

National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China.

Growing evidence suggests that relative carbohydrate intake affects depression; however, the association between carbohydrates and depression remains controversial. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using genetic variants associated with relative carbohydrate intake (N = 268,922) and major depressive disorder (N = 143,265) from the largest available genome-wide association studies. MR evidence suggested a causal relationship between higher relative carbohydrate intake and lower depression risk (odds ratio, 0.42 for depression per one-standard-deviation increment in relative carbohydrate intake; 95% confidence interval, 0.28 to 0.62; P = 1.49 × 10). Multivariable MR indicated that the protective effect of relative carbohydrate intake on depression persisted after conditioning on other diet compositions. The mediation analysis via two-step MR showed that this effect was partly mediated by body mass index, with a mediated proportion of 15.4% (95% confidence interval, 6.7% to 24.1%). These findings may inform prevention strategies and interventions directed towards relative carbohydrate intake and depression.
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http://dx.doi.org/10.1038/s41562-022-01412-9DOI Listing
July 2022

lncRNA SNHG1 regulates odontogenic differentiation of human dental pulp stem cells via miR-328-3p/Wnt/β-catenin pathway.

Stem Cell Res Ther 2022 07 15;13(1):311. Epub 2022 Jul 15.

Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.

Background: Elucidating the mechanism of odontogenic differentiation of human dental pulp stem cells (hDPSCs) is the key to in-depth mastery and development of regenerative endodontic procedures (REPs). In odontogenic differentiation, lncRNAs have a regulatory role. The goal of this research is to determine the involvement of short nucleolar RNA host gene 1 (SNHG1) in hDPSCs' odontogenic differentiation and the mechanism that underpins it.

Methods: hDPSCs were isolated from the dental pulp tissue of healthy immature permanent teeth. Follow-up experiments were performed when the third generation of primary cells were transfected. The proliferation ability was measured by CCK-8. The biological effects of SNHG1 and miR-328-3p were determined by real-time quantitative polymerase chain reaction (qRT-PCR), western blot (WB), alkaline phosphatase (ALP) staining and activity, alizarin red S staining (ARS) and quantification, and immunofluorescence staining. The binding of SNHG1 and miR-328-3p was confirmed using a dual-luciferase reporter assay. qRT-PCR and WB were used to determine whether the canonical Wnt/β-catenin pathway was activated.

Results: On the 0th, 3rd, and 7th days of odontogenic differentiation of hDPSCs, SNHG1 showed a gradual up-regulation trend. SNHG1 overexpression enhanced the mRNA and protein expression of dentin sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP-1) and ALP. We found that SNHG1 could bind to miR-328-3p. miR-328-3p inhibited the odontogenic differentiation of hDPSCs. Therefore, miR-328-3p mimics rescued the effect of SNHG1 overexpression on promoting odontogenic differentiation. In addition, SNHG1 inhibited Wnt/β-catenin pathway via miR-328-3p in odontogenic differentiation of hDPSCs.

Conclusion: lncRNA SNHG1 inhibits Wnt/β-catenin pathway through miR-328-3p and then promotes the odontogenic differentiation of hDPSCs.
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http://dx.doi.org/10.1186/s13287-022-02979-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284872PMC
July 2022

Anxiety and Its Influencing Factors in Patients With Drug-Induced Liver Injury.

Front Psychol 2022 28;13:889487. Epub 2022 Jun 28.

Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, China.

Objective: This study aims to investigate anxiety and its influencing factors in patients with drug-induced liver injury (DILI).

Materials And Methods: Ninety-four patients with DILI were enrolled and evaluated with a self-rating anxiety scale (SAS). According to the anxiety score, they were divided into four groups: the non-anxiety, mild anxiety, moderate anxiety, or severe anxiety groups, and the scores were analyzed based on demographic and biochemical indicators.

Results: Of the 94 patients with DILI, 63 did not have anxiety and 31 had anxiety (32.9%), of which 27 had mild, 3 had moderate, and 1 had severe anxiety. There were no statistically significant differences in gender, age, occupation, and level of education between the groups ( = 1.42, = 2.361, = 6.751, = 1.796, and > 0.05); anxiety score and degree of anxiety between the types of drugs that led to the liver injury ( = 0.812, = 1.712, and > 0.05); anxiety score between the different degrees of liver injury ( = 2.836, = 4.957, > 0.05); or length of hospital stay or prognosis between the degrees of anxiety ( = 1.487, = 0.761, > 0.05). However, there were statistically significant differences in the degree of anxiety between different degree and types of liver injury ( = 7.981, = 8.208, < 0.05).

Conclusion: Patients with DILI may have anxiety, especially mild anxiety. The occurrence of anxiety in patients with DILI is not related to gender, age, occupation, or level of education but may be related to the degree and type of liver injury. Anxiety has no impact on the length of stay in hospital or the prognosis of the DILI. These findings may contribute to the development of management strategies for patients with DILI.
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http://dx.doi.org/10.3389/fpsyg.2022.889487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274128PMC
June 2022

Radiomics model based on multi-sequence MR images for predicting preoperative immunoscore in rectal cancer.

Radiol Med 2022 Jul 13;127(7):702-713. Epub 2022 Jul 13.

Department of Radiology, China-Japan Union Hospital of Jilin University, NO. 126 Xiantai Street, Changchun, 130033, China.

Purpose: To establish and validate a radiomics model based on multi-sequence magnetic resonance (MR) images for preoperative prediction of immunoscore in rectal cancer.

Materials And Methods: This retrospective study included 133 patients with pathologically confirmed rectal cancer after surgical resection who underwent MR examination before treatment within two weeks. All patients were randomly divided into training cohort (n = 92) and validation (n = 41) cohort according to a ratio of 7:3. The volumes of interest were manually delineated in the T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) images, from which a total of 804 radiomics features were extracted. Thereafter, we used Spearman correlation analysis and gradient boosting decision tree (GBDT) algorithm to select the strongest features, and the radiomics scores were established using multivariate logistic regression algorithm, including two single-mode models and two dual-mode models. The predictive performance and the clinical usefulness of the model were assessed by the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA).

Results: Integrated model A based on T2WI and ADC images showed a better predictive performance, which yielded an AUC of 0.770 (95% CI 0.673-0.867) in the training cohort and 0.768 (95% CI 0.619-0.917) in the validation cohort. Calibration curve showed good agreement between predicted results of the model and actual events, and DCA indicated good clinical usefulness. Moreover, stratification analysis proved that the integrated model A had strong robustness.

Conclusions: Integrated model A based on T2WI and ADC images has the potential to be used as a non-invasive tool for preoperative prediction of immunoscore in rectal cancer. It may be useful in evaluating prognosis and guiding individualized immunotherapy of patients.
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http://dx.doi.org/10.1007/s11547-022-01507-3DOI Listing
July 2022

Metabolic engineering of the violacein biosynthetic pathway toward a low-cost, minimal-equipment lead biosensor.

Biosens Bioelectron 2022 Oct 6;214:114531. Epub 2022 Jul 6.

National Key Clinical Specialty of Occupational Diseases, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, 518020, China. Electronic address:

Metabolic engineered bacteria have been successfully employed to produce various natural colorants, which are expected to be used as the visually recognizable signals to develop mini-equipment biological devices for monitoring toxic heavy metals. The violacein biosynthetic pathway has been reconstructed in Escherichia coli (E. coli). Here the successful production of four violacein derivatives was achieved by integrating metabolic engineering and synthetic biology. Lead binding to the metalloregulator enables whole-cell colorimetric biosensors capable of assessing bioavailable lead. Deoxyviolacein-derived signal showed the most satisfied biosensing properties among prodeoxyviolacein (green), proviolacein (blue), deoxyviolacein (purple), and violacein (navy). The limit of detection (LOD) of pigment-based biosensors was 2.93 nM Pb(II), which is lower than that of graphite furnace atomic absorption spectrometry. Importantly, a good linear dose-response model in a wide dose range (2.93-6000 nM) was obtained in a non-cytotoxic deoxyviolacein-based biosensor, which was significantly better than cytotoxic violacein-based biosensor (2.93-750 nM). Among ten metal ions, only Cd(II) and Hg(II) exerted a slight influence on the response of the deoxyviolacein-based biosensor toward Pb(II). The deoxyviolacein-based biosensor was validated in detecting bioaccessible Pb(II) in environmental samples. Factors such as low cost and minimal-equipment requirement make this biosensor a suitable biological device for monitoring toxic lead in the environment.
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http://dx.doi.org/10.1016/j.bios.2022.114531DOI Listing
October 2022

Exposing Single Ni Atoms in Hollow S/N-Doped Carbon Macroporous Fibers for Highly Efficient Electrochemical Oxygen Evolution.

Adv Mater 2022 Jul 7:e2203442. Epub 2022 Jul 7.

School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore, 637459, Singapore.

The development of efficient and cost-effective electrocatalysts toward the oxygen evolution reaction (OER) is highly desirable for clean energy and fuel conversion. Herein, the facile preparation of Ni single atoms embedded hollow S/N-doped carbon macroporous fibers (Ni [email protected]/N-CMF) as efficient catalysts for OER through pyrolysis of designed CdS-NiS /polyacrylonitrile composite fibers is reported. Specifically, CdS provides the sulfur source for the doping of polyacrylonitrile-derived carbon matrix and simultaneously creates the hollow macroporous structure, while NiS is first reduced to nanoparticles and finally evolves into single Ni atoms through the atom migration-trapping strategy. Benefiting from the abundantly exposed single Ni atoms and hollow macroporous structure, the resultant Ni [email protected]/N-CMF electrocatalysts deliver outstanding activity and stability for OER. Specifically, it needs an overpotential of 285 mV to achieve the benchmark current density of 10 mA cm with a small Tafel slope of 50.8 mV dec .
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http://dx.doi.org/10.1002/adma.202203442DOI Listing
July 2022

Correlation of Blood Lipid and Serum Inflammatory Factor Levels With Hypertensive Disorder Complicating Pregnancy.

Front Surg 2022 17;9:917458. Epub 2022 Jun 17.

Department of obstetrics, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China.

Purpose: To explore the changes of blood lipid and serum inflammatory factors in pregnant women with hypertensive disorder complicating pregnancy (HDP) and the relationship with disease development.

Methods: 107 pregnant women with HDP who had regular prenatal examination in our hospital from July 2018 to July 2021 were selected as the research objects. According to the severity of the disease, they were divided into gestational hypertension group, mild preeclampsia group and severe preeclampsia group. 30 healthy pregnant women who underwent prenatal examination in the same period were selected as the healthy group. Serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), lipoprotein-associated phospholipaseA2 (Lp-PLA2), C- reactive protein (CRP), interleukin -6 (IL-6), tumor necrosis factor-α (TNF-α) were measured. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of blood lipid and serum inflammatory factors in pregnant women with HDP.

Results: The levels of serum TC, TG and LDL-C increased with the progression of HDP, the level of serum HDL-C decreased with the progression of HDP ( < 0.05). The levels of serum Lp-PLA2, CRP, IL-6 and TNF-α increased with the progression of HDP ( < 0.05). The AUC of serum TC, TG, HDL-C and LDL-C levels for predicting HDP were 0.759, 0.854, 0.770 and 0.785, respectively. The AUC of serum Lp-PLA2, CRP, IL-6 and TNF-α levels for predicting HDP were 0.873, 0.991, 0.966 and 0.999, respectively.

Conclusion: The levels of blood lipid and serum inflammatory factor are closely related to HDP, which has certain value in predicting the occurrence and development of HDP.
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http://dx.doi.org/10.3389/fsurg.2022.917458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249135PMC
June 2022
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