Publications by authors named "Lin Chen"

4,944 Publications

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Generating an oilseed rape mutant with non-abscising floral organs using CRISPR/Cas9 technology.

Plant Physiol 2022 Aug 11. Epub 2022 Aug 11.

Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, Yangzhou 225009, China.

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http://dx.doi.org/10.1093/plphys/kiac364DOI Listing
August 2022

Comparison of the Diagnostic Accuracy of Percutaneous Fistula Contrast-Enhanced Ultrasound Combined with Transrectal 360° 3-D Imaging and Conventional Transrectal Ultrasound in Complex Anal Fistula.

Ultrasound Med Biol 2022 Aug 7. Epub 2022 Aug 7.

Department of Ultrasound, Clinical Medical College, Chengdu, China; First Affiliated Hospital of Chengdu Medical College, Chengdu, China. Electronic address:

This study compared the diagnostic accuracy of percutaneous fistula contrast-enhanced ultrasound (CEUS) combined with 360° 3-D transrectal ultrasound (TRUS) imaging (CEUS + 360°-TRUS) with that of conventional transrectal ultrasound in the diagnosis of complex anal fistulas. A total of 156 patients clinically diagnosed with complex anal fistula from January 2020 to December 2021 were studied and randomly divided into an experimental group (n = 82) and a control group (n = 74). Patients in the experimental group were examined by percutaneous fistula CEUS combined with CEUS + 360°-TRUS, while patients in the control group were examined using TRUS. The detection of fistulas (main tract, branch and internal orifice) and the accuracy of Parks classification were compared between the two groups. Recurrences were followed up at 1, 3 and 6 mo after the surgery. A total of 156 patients were included, aged 23-68 y (average: 37.7 ± 18.2 y). In both groups, the course of disease was <1 mo in 128 cases, 1-2 mo in 22 cases and >3 mo in 6 cases. A total of 474 fistulas were confirmed by surgery in the aforementioned patients, including 224 main fistulas, 250 branch pipes and 254 internal orifices. The CEUS + 360°-TRUS group had 96.87%, 90.41% and 90.14% diagnostic accuracy for the main tract, branch and internal orifice, which was statistically significant (p < 0.001) compared with the 85.00%, 70.00% and 72.46% for the TRUS group, respectively. The overall accuracy of Parks classification of anal fistula in the CEUS + 360°-TRUS group was significantly higher than that in the TRUS group (90.24% vs. 78.38%, p < 0.001). After 6 mo of follow-up, the recurrence rate in the CEUS + 360°-TRUS group was 4.87%, and the recurrence rate in the TRUS group was 18.91%. Percutaneous fistula CEUS combined with transrectal 360° 3-D imaging has significantly higher accuracy than conventional TRUS in the diagnosis of complex anal fistula, especially for anal fistula branches, internal openings and Parks classification and is beneficial in reducing post-operative occurrence of complex anal fistulas.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2022.06.013DOI Listing
August 2022

Risk of Dementia Associated With Atrial Cardiopathy: The ARIC Study.

J Am Heart Assoc 2022 Aug 10:e025646. Epub 2022 Aug 10.

Cardiovascular Division, Department of Medicine University of Minnesota Medical School Minneapolis MN.

Background The contribution of atrial cardiopathy to dementia risk is uncharacterized. We aimed to evaluate the association of atrial cardiopathy with incident dementia and potential mediation by atrial fibrillation (AF) and stroke. Methods and Results We conducted a prospective cohort analysis of participants in the ARIC (Atherosclerosis Risk in Communities) study attending visit 5 (2011-2013). We used Cox regression to determine the association between atrial cardiopathy and risk of dementia. Structural equation modeling methods were used to determine potential mediation by AF and/or stroke. Atrial cardiopathy was defined if ≥1 of the following at visit 5: P-wave terminal force >5000 mV·ms in ECG lead V1, NT-proBNP (N-terminal pro-brain natriuretic peptide) >250 pg/mL or left atrial volume index ≥34 mL/m by transthoracic echocardiography. We repeated our analysis necessitating ≥2 markers to define atrial cardiopathy. The prevalence of atrial cardiopathy was 34% in the 5078 participants (mean age 75 years, 59% female, 21% Black adults), with 763 participants developing dementia. Atrial cardiopathy was significantly associated with dementia (adjusted HR, 1.35 [95% CI, 1.16-1.58]), with strengthening of the effect estimate when necessitating ≥2 biomarkers (adjusted HR, 1.54 [95% CI, 1.25-1.89]). There was an increased risk of dementia among those with atrial cardiopathy when excluding those with AF (adjusted HR, 1.31 [95% CI, 1.12-1.55]) or stroke (adjusted HR, 1.28 [95% CI, 1.09-1.52]). The proportion of the effect mediated by AF was 4% (=0.005), and 9% was mediated by stroke (=0.048). Conclusions Atrial cardiopathy was significantly associated with an increased risk of dementia, with only a small percent mediation of the effect by AF or stroke.
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http://dx.doi.org/10.1161/JAHA.121.025646DOI Listing
August 2022

Relation of Electrocardiographic Abnormal P-Wave Axis With Stroke Mortality in the General Population.

Am J Cardiol 2022 Aug 6. Epub 2022 Aug 6.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.

The link between abnormal P-wave axis (aPWA) and incident ischemic stroke is well established. However, studies examining the association between aPWA and fatal stroke are rare. We hypothesized that aPWA is associated with fatal stroke. We examined the association of abnormal aPWA with stroke mortality in 7,359 participants (60.0 ± 13.4 years, 51.9% women, 49.8% White) without cardiovascular (CV) disease (CVD) from the Third National Health and Nutrition Examination Survey. aPWA was defined as any value <0 or >75. The National Death Index was used to identify the date and cause of death. Cox proportional hazard analysis was used to examine the association between baseline aPWA with stroke mortality. Over a median follow-up of 14 years, 189 stroke deaths occurred. During follow-up, stroke mortality was more common in those with aPWA than those without aPWA (3.5% vs 2.2%, respectively; p = 0.002). In a multivariable-adjusted model, aPWA was associated with a 44% increased risk of stroke mortality (hazard ratio [HR] 95% confidence interval [CI] 1.44 [1.05 to 1.99]). This association was stronger in men than in women (HR 95% CI 2.29 [1.42 to 3.67] vs 1.00 [0.64 to 1.55]), respectively; p-interaction = 0.04) and among non-Whites than Whites (HR 95% CI 2.20 [1.39 to 3.46] vs. 1.07 [0.68 to 1.69], respectively; p-interaction = 0.09). The annualized stroke death rates/1,000 participants across levels of CHA2DS2-VASc scores were higher in those with than without aPWA. In conclusion, aPWA, a marker of atrial cardiopathy, is associated with an increased risk of stroke mortality, especially among men and non-Whites. Whether intensive risk factor modifications in those with aPWA would reduce the risk of stroke and thus, stroke mortality needs further investigation.
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http://dx.doi.org/10.1016/j.amjcard.2022.06.051DOI Listing
August 2022

Serum hyperhomocysteine and cognitive impairment in first-episode patients with schizophrenia: moderated by brain cortical thickness.

Neurosci Lett 2022 Aug 6:136826. Epub 2022 Aug 6.

Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China. Electronic address:

The mechanism by which high homocysteine (HCY) may aggravate cognitive impairment in patients with schizophrenia is not well understood. We aimed to test the hypothesis that hyperhomocysteinaemia may exacerbate cognitive deficits by mediating the decrease in cortical thickness in patients with schizophrenia. One hundred and sixty-seven first-episode patients with schizophrenia (FEPS) and 120 healthy controls (HCs) were included. Psychopathology and cognitive function were assessed using the Positive and Negative Symptom Scale and Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), respectively. Brain cortical thickness was measured by 3.0T high-resolution magnetic resonance imaging. Serum HCY levels were tested using a sandwich enzyme-linked immunosorbent assay. Our findings showed that HCY levels in the FEPS were significantly higher than those in the HCs (P<0.001). The MCCB total and subtest scores in the patients were significantly lower than those in the HCs (P<0.001). The HCs had significantly higher cortical thickness than the patients (P<0.001). Serum HCY levels were negatively correlated with Working Memory, Attention/Vigilance, and MCCB total scores in the FEPS (P<0.05). Brain cortical thickness had positive moderating effects on cognitive impairment in FEPS with high HCY after controlling for sex, age, and education (P<0.05). In HCs with high HCY, brain cortical thickness had no mediating or moderating effects on cognitive impairment. Compared with HCs, FEPS had thinner grey matter thickness, furthermore, the grey matter thickness might play a crucial role in relationship between high HCY and cognitive deficits.
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http://dx.doi.org/10.1016/j.neulet.2022.136826DOI Listing
August 2022

Relationships between self-efficacy, coping-style and quality of work-life among nursing managers in China: A cross-sectional study.

J Nurs Manag 2022 Aug 9. Epub 2022 Aug 9.

Department of Nursing, Zigong First People's Hospital, Zigong, Sichuan, China.

Aim: To investigate the quality of work-life among nursing managers in China and analyze the relationships between self-efficacy, coping-style, and quality of work-life.

Background: Self-efficacy, coping-style, and quality of work-life play significant roles in the stability of nursing teams, the quality of clinical care, and patient safety. Although some factors influencing quality of work-life have been identified, there is no large-scale study of the relationships among self-efficacy, coping-style, and quality of work-life of nursing managers. Strategies to strengthen the quality of work-life of nursing managers should be developed by exploring the relationships between the three variables.

Methods: A nationwide cross-sectional study was conducted. A total of 1498 nursing managers from 51 tertiary general hospitals in 20 provinces in China were selected for the study using multistage stratified proportional sampling. Registered full-time nursing managers with more than one year of management experience were eligible for the study. The participants completed online questionnaires to assess their self-efficacy, coping-style, and work-related quality of life. The data were analyzed using descriptive analysis, Pearson's correlation, hierarchical multiple linear regression, and structural equation modelling to verify the relationships between variables.

Results: The quality of work-life score for the nursing managers surveyed was 3.74 ± 0.56 out of a possible five. Self-efficacy was positively correlated with quality of work-life (β = 0.484, P < 0.01) over all demographic variables. Positive coping was also positively associated with quality of work-life (β = 0.404, P < 0.01). Self-efficacy and positive coping explained 22.7% and 14.2% of the variance in the quality of work-life, respectively. Structural equation modelling indicated that self-efficacy positively and directly predicted the quality of work-life (β = 0.395, P < 0.001), and indirectly affected quality of work-life via positive coping (β = 0.186, P < 0.001), but not via negative coping (β = 0.005, P > 0.05). The final model could explain 44% of the variance in the quality of work-life.

Conclusion: Self-efficacy was positively correlated with quality of work-life among Chinese nursing managers, and positive coping partially mediated this relationship. The results suggest that self-efficacy and positive coping are pivotal facilitators for improving the quality of work-life and need to be taken into account in measures to improve the quality of work-life of nursing managers.

Implications For Nursing Management: Hospital administrators should recognize the importance of nursing managers' work-life quality to promote both the stability of nursing teams and the quality of clinical care and safety provided. They should help nursing managers foster self-efficacy and active coping abilities through incentive measures and provide positive coping training courses to enhance their quality of work-life.
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http://dx.doi.org/10.1111/jonm.13753DOI Listing
August 2022

Identification of Immune-Related Hub Genes in Parkinson's Disease.

Front Genet 2022 22;13:914645. Epub 2022 Jul 22.

Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Parkinson's disease (PD) is a common, age-related, and progressive neurodegenerative disease. Growing evidence indicates that immune dysfunction plays an essential role in the pathogenic process of PD. The objective of this study was to explore potential immune-related hub genes and immune infiltration patterns of PD. The microarray expression data of human postmortem substantia nigra samples were downloaded from GSE7621, GSE20141, and GSE49036. Key module genes were screened weighted gene coexpression network analysis, and immune-related genes were intersected to obtain immune-key genes. Functional enrichment analysis was performed on immune-key genes of PD. In addition to, immune infiltration analysis was applied by a single-sample gene set enrichment analysis algorithm to detect differential immune cell types in the substantia nigra between PD samples and control samples. Least absolute shrinkage and selection operator analysis was performed to further identify immune-related hub genes for PD. Receiver operating characteristic curve analysis of the immune-related hub genes was used to differentiate PD patients from healthy controls. Correlations between immune-related hub genes and differential immune cell types were assessed. Our findings identified four hub genes (, , , and ) and seven immune cell types (neutrophils, T follicular helper cells, myeloid-derived suppressor cells, type 1 helper cells, immature B cells, immature dendritic cells, and CD56 bright natural killer cells). The area under the curve (AUC) value of the four-gene-combined model was 0.92. The AUC values of each immune-related hub gene (, , , and ) were 0.81, 0.78, 0.78, and 0.76, respectively. In conclusion, , , , and were identified as being associated with the pathogenesis of PD and should be further researched.
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http://dx.doi.org/10.3389/fgene.2022.914645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353688PMC
July 2022

Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets.

Cell Stem Cell 2022 Aug;29(8):1229-1245.e7

Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China; South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. Electronic address:

Reprogramming somatic cells into megakaryocytes (MKs) would provide a promising source of platelets. However, using a pharmacological approach to generate human MKs from somatic cells remains an unmet challenge. Here, we report that a combination of four small molecules (4M) successfully converted human cord blood erythroblasts (EBs) into induced MKs (iMKs). The iMKs could produce proplatelets and release functional platelets, functionally resembling natural MKs. Reprogramming trajectory analysis revealed an efficient cell fate conversion of EBs into iMKs by 4M via the intermediate state of bipotent precursors. 4M induced chromatin remodeling and drove the transition of transcription factor (TF) regulatory network from key erythroid TFs to essential TFs for megakaryopoiesis, including FLI1 and MEIS1. These results demonstrate that the chemical reprogramming of cord blood EBs into iMKs provides a simple and efficient approach to generate MKs and platelets for clinical applications.
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http://dx.doi.org/10.1016/j.stem.2022.07.004DOI Listing
August 2022

A novel lytic phage potentially effective for phage therapy against Burkholderia pseudomallei in the tropics.

Infect Dis Poverty 2022 Aug 4;11(1):87. Epub 2022 Aug 4.

Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine and The Second Affiliated Hospital, Hainan Medical University, Haikou, Hainan, China.

Background: Burkholderia pseudomallei is a tropical pathogen that causes melioidosis. Its intrinsic drug-resistance is a leading cause of treatment failure, and the few available antibiotics require prolonged use to be effective. This study aimed to assess the clinical potential of B. pseudomallei phages isolated from Hainan, China.

Methods: Burkholderia pseudomallei strain (HNBP001) was used as the isolation host, and phages were recovered from domestic environmental sources, which were submitted to the host range determination, lytic property assays, and stability tests. The best candidate was examined via the transmission electron microscope for classification. With its genome sequenced and analyzed, its protective efficacy against B. pseudomallei infection in A549 cells and Caenorhabditis elegans was evaluated, in which cell viability and survival rates were compared using the one-way ANOVA method and the log-rank test.

Results: A phage able to lyse 24/25 clinical isolates was recovered. It was classified in the Podoviridae family and was found to be amenable to propagation. Under the optimal multiplicity of infection (MOI) of 0.1, an eclipse period of around 20 min and a high titer (10 PFU/ml) produced within 1 h were demonstrated. This phage was found stabile at a wide range of temperatures (24, 37, 40, 50, and 60 °C) and pH values (3-12). After being designated as vB_BpP_HN01, it was fully sequenced, and the 71,398 bp linear genome, containing 93 open reading frames and a tRNA-Asn, displayed a low sequence similarity with known viruses. Additionally, protective effects of applications of vB_BpP_HN01 (MOI = 0.1 and MOI = 1) alone or in combination with antibiotics were found to improve viability of infected cells (70.6 ± 6.8%, 85.8 ± 5.7%, 91.9 ± 1.8%, and 96.8 ± 1.8%, respectively). A significantly reduced mortality (10%) and a decreased pathogen load were demonstrated in infected C. elegans following the addition of this phage.

Conclusions: As the first B. pseudomallei phage was isolated in Hainan, China, phage vB_BpP_HN01 was characterized by promising lytic property, stability, and efficiency of bacterial elimination during the in vitro/vivo experiments. Therefore, we can conclude that it is a potential alternative agent for combating melioidosis.
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http://dx.doi.org/10.1186/s40249-022-01012-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351088PMC
August 2022

The Sclerotinia sclerotiorum-inducible promoter pBnGH17D7 in Brassica napus: isolation, characterization and application in host-induced gene silencing.

J Exp Bot 2022 Aug 5. Epub 2022 Aug 5.

Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, Yangzhou 225009, China.

Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum, is among the most devastating diseases in Brassica napus worldwide. Conventional breeding for SSR resistance in Brassica species is challenging due to the limited availability of resistant germplasm. Therefore, genetic engineering is an attractive means for developing SSR-resistant Brassica crops. Compared with constitutive promoter, S. sclerotiorum-inducible promoter would avoid ectopic expression of defense genes that may cause plant growth deficits. In this study, we generated a S. sclerotiorum-inducible promoter. pBnGH17D7, from the promoter of B. napus glycosyl hydrolase 17 gene (pBnGH17). Specifically, 5'-deletion and promoter activity analyses in transgenic A. thaliana plants defined a 189-bp region of pBnGH17, that was indispensable for S. sclerotiorum-induced response. Compared with pBnGH17, pBnGH17D7 showed a similar response upon S. sclerotiorum infection, but lower activity in plant tissues in the absence of S. sclerotiorum infection. Moreover, we revealed that the transcription factor BnTGA7 directly binds to the TGACG motif in pBnGH17D7 to activate BnGH17. Ultimately, pBnGH17D7 was exploited for engineering Sclerotinia-resistant B. napus via host-induced gene silencing. It induces high expression of small interfering RNAs against S. sclerotiorum pathogenic-factor gene specifically during infection, leading to increased resistance.
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http://dx.doi.org/10.1093/jxb/erac328DOI Listing
August 2022

A 619-pixel machine vision enhancement chip based on two-dimensional semiconductors.

Sci Adv 2022 Aug 3;8(31):eabn9328. Epub 2022 Aug 3.

State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai 200433, China.

The rapid development of machine vision applications demands hardware that can sense and process visual information in a single monolithic unit to avoid redundant data transfer. Here, we design and demonstrate a monolithic vision enhancement chip with light-sensing, memory, digital-to-analog conversion, and processing functions by implementing a 619-pixel with 8582 transistors and physical dimensions of 10 mm by 10 mm based on a wafer-scale two-dimensional (2D) monolayer molybdenum disulfide (MoS). The light-sensing function with analog MoS transistor circuits offers low noise and high photosensitivity. Furthermore, we adopt a MoS analog processing circuit to dynamically adjust the photocurrent of individual imaging sensor, which yields a high dynamic light-sensing range greater than 90 decibels. The vision chip allows the applications for contrast enhancement and noise reduction of image processing. This large-scale monolithic chip based on 2D semiconductors shows multiple functions with light sensing, memory, and processing for artificial machine vision applications, exhibiting the potentials of 2D semiconductors for future electronics.
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http://dx.doi.org/10.1126/sciadv.abn9328DOI Listing
August 2022

Palladium-Catalyzed Direct Synthesis and Insecticidal Activity of Arylmatrine Derivatives.

J Nat Prod 2022 Aug 3. Epub 2022 Aug 3.

Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, People's Republic of China.

Pd(OAc)/NiXantphos efficiently catalyzed the direct arylation at the C-14 position of matrine, leading to 38 arylmatrine derivatives (- and -) in good yields. Most of these matrine analogues showed enhanced insecticidal effects superior to the parent compound matrine. Among them, the 3,5-diphenylbenzene analogue () exhibited the most potent in vivo antifeedant activity (EC = 0.19 mg/mL) against (Hübner), with approximately 25-fold more activity than matrine, for which the preliminary mechanism of action was verified through enzyme inhibition activities and molecular docking. Compound as well displayed in vitro antiproliferation activity on Sf9 insect cells (IC = 8.1 μM), and its apoptotic induction effect was illustrated by morphological observation and DNA fragment analysis. Overall, the above results provide further information on the potential of arylmatrine-type lead compounds for the prevention and control of insect pests.
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http://dx.doi.org/10.1021/acs.jnatprod.2c00417DOI Listing
August 2022

Development of a HPLC-UV Method for the Separation and Quantification of Hesperidin, Neohesperidin, Neohesperidin Dihydrochalcone and Hesperetin.

Nat Prod Res 2022 Aug 1:1-5. Epub 2022 Aug 1.

Shandong Benyue Biological Technology Co., Ltd, Shandong, P. R. China.

An analysis method was developed for the separation and quantification of hesperidin, neohesperidin, neohesperidin dihydrochalcone and hesperetin by using HPLC-UV. Single factor experiments and Box-Behnken Designs were used to optimize separation of four flavonoids, in which a gradient elution method was adopted with 99% acetonitrile and 0.1% formic acid as mobile phases at a flow rate of 0.9 mL/min. A C column was used with a column temperature of 35 °C. LODs and LOQs were below 0.84 µg/mL and 2.84 µg/mL, respectively. Linearity with good correlation coefficients ( > 0.99,  = 5) was attained, recovery rate of four flavonoids ranged from 88% to 130%, the RSD indicating results precision for analyzing hesperidin, neohesperidin, neohesperidin dihydrochalcone and hesperetin ranged from 1.2% to 4.6%. Finally, the present method could be successfully applied to identify and quantify hesperidin, neohesperidin and hesperetin in and .
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http://dx.doi.org/10.1080/14786419.2022.2104275DOI Listing
August 2022

Single-frequency Tm-doped fiber laser with 215 mW at 2.05 µm based on a Tm/Ho-codoped fiber saturable absorber.

Opt Lett 2022 Aug;47(15):3964-3967

We demonstrate an efficient single-frequency Tm-doped fiber laser at 2050 nm. A ring cavity scheme is employed to boost the net gain at the wavelength. A piece of Tm/Ho-codoped fiber with an absorption coefficient at 2050 nm higher than that of a Tm-doped fiber is used to establish the dynamic Bragg grating for enhancing the frequency selection capability. A single-frequency output of 215 mW is obtained under 2 W of 1570-nm pump power, with the slope efficiency being 22%. To the best of our knowledge, this is the highest single-frequency all-fiber laser oscillator output power above 2 µm.
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http://dx.doi.org/10.1364/OL.463202DOI Listing
August 2022

Combination of Low-Dose Gemcitabine and PD-1 Inhibitors for Treatment in Patients With Advanced Malignancies.

Front Immunol 2022 13;13:882172. Epub 2022 Jul 13.

Department of Immunotherapy, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Purpose: This study determined the efficacy of low-dose gemcitabine combined with programmed death-1 (PD-1) inhibitors for treating multiple malignancies, providing a cost-effective and safe treatment option.

Study Design: This study included 61 patients with advanced solid tumors treated with low-dose gemcitabine combined with PD-1 inhibitors at the Henan Cancer Hospital between January 2018 and February 2022. We retrospectively reviewed medical records to evaluate several clinical factors, including progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and objective response to treatment.

Results: Sixty-one patients received treatment with low-dose gemcitabine combined with PD-1 inhibitors. The objective response rate (ORR) was 29.5% and the disease control rate (DCR) was 62.3%. The median PFS was 4.3 months (95% confidence interval, 2.3 to 6.3 months) and the median OS was 15.0 months (95% confidence interval, 8.8 to 21.2 months). Hematological toxicity, mainly leukopenia or thrombocytopenia, was the most common AE, with any-grade and grade 3/4 hematological toxicity reported in 60.7 and 13.1% of patients, respectively.

Conclusions: Low-dose gemcitabine combined with PD-1 inhibitors may offer a novel treatment option for patients with advanced malignancies.
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http://dx.doi.org/10.3389/fimmu.2022.882172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328170PMC
July 2022

Long-term maintenance of synaptic plasticity by Fullerenol Ameliorates lead-induced-impaired learning and memory in vivo.

J Nanobiotechnology 2022 Aug 1;20(1):348. Epub 2022 Aug 1.

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.

Fullerenol, a functional and water-soluble fullerene derivative, plays an important role in antioxidant, antitumor and antivirus, implying its enormous potential in biomedical applications. However, the in vivo performance of fullerenol remains largely unclear. We aimed to investigate the effect of fullerenol (i.p., 5 mg/kg) on the impaired hippocampus in a rat model of lead exposure. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is a kind of newly developed soft-ionization mass spectrometry technology. In the present study, an innovative strategy for biological distribution analysis using MALDI-TOF-MS confirmed that fullerenol could across the blood-brain barrier and accumulate in the brain. Results from behavioral tests showed that a low dose of fullerenol could improve the impaired learning and memory induced by lead. Furthermore, electrophysiology examinations indicated that this potential repair effect of fullerenol was mainly due to the long-term changes in hippocampal synaptic plasticity, with enhancement lasting for more than 2-3 h. In addition, morphological observations and biochemistry analyses manifested that the long-term change in synaptic efficacy was accompanied by some structural alteration in synaptic connection. Our study demonstrates the therapeutic feature of fullerenol will be beneficial to the discovery and development as a new drug and lays a solid foundation for further biomedical applications of nanomedicines.
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http://dx.doi.org/10.1186/s12951-022-01550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341061PMC
August 2022

Use of the bibliometric in rare diseases: taking Wilson disease personally.

Orphanet J Rare Dis 2022 07 29;17(1):297. Epub 2022 Jul 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun RoadZhejiang Province, Hangzhou, 310003, China.

Background: Bibliometric have been widely applied to the evaluation of academic productivity. However, those of individuals or institutions on a specific disease have not been explored. The aim of the present study is to conduct a bibliometric analysis of particular rare disease and investigate whether those doctors and hospitals with higher index screened by this method specialize in this disease.

Methods: A representative rare disease, Wilson disease (WD), was searched on Clarivate Analytics' Web of Science and Elsevier's Scopus, which was published in English between 1 January 2001 and 31 December 2020. Clinical authors and medical institutions with the most papers were screened, and their total number of publications and citations, h-index and g-index were computed and then ranked by h-index.

Results: A total of 6856 and 6193 papers and 200 and 160 authors were got from WoS and Scopus, respectively. Scopus provided 160 institutions. The above bibliometric indices were calculated in 100 researchers and 80 institutions, and top 30 authors (Top-30a) and top 20 institutions (Top-20i) of them based on the h-index were listed in the tables. Top-30a came from seven specialties and 13 countries whose median (interquartile range) h-index was 14 (12-19.5) (range 10-28) which was located between associate and full professors in some other disciplines. Top-20i was distributed in 13 countries whose mean ± standard deviation of the h-index was 15 ± 4.9 (range 10-27).

Conclusions: The related specialists and medical institutions of WD screened by specific disease bibliometric analysis are eminent and credible and benefit WD patients to obtain reliable medical treatment. This model may be suitable for other rare diseases.
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http://dx.doi.org/10.1186/s13023-022-02459-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335981PMC
July 2022

Inhibition of CCL28/CCR10-mediated eNOS Downregulation Improves Skin Wound Healing in the Obesity-induced Mouse Model of Type 2 Diabetes.

Diabetes 2022 Jul 28. Epub 2022 Jul 28.

Departments of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA.

Chronic, non-healing skin wounds such as diabetic foot ulcers (DFUs) are common in patients with type 2 diabetes. Here, we investigated the role of chemokine CCL28 and its receptor CCR10 in downregulation of endothelial nitric oxide synthase (eNOS) in association with delayed skin wound healing in the db/db mouse model of type 2 diabetes. We observed reduced eNOS expression and elevated CCL28/CCR10 levels in dorsal skin of db/db mice and subdermal leg biopsies from human subjects with type 2 diabetes. Further interrogation revealed that overexpression of CCR10 reduced eNOS expression, NO bioavailability, and tube formation of human dermal microvascular endothelial cells (HDMVECs) in vitro which was recapitulated in mouse dorsal skin. In addition, incubation of HDMVECs with CCL28 led to internalization of the CCR10/eNOS complex and co-localization with lysosome-associated membrane protein-1. Finally, topical application of myristoylated CCR10 binding domain 7 amino acid (Myr-CBD7) peptide prevented CCR10-eNOS interaction and subsequent eNOS downregulation, enhanced eNOS/NO levels, eNOS/VEGF-R2+ microvessel density, and blood perfusion, reduced inflammatory cytokine levels, and importantly, decreased wound healing time in db/db mice. Thus, endothelial cell CCR10 activation in genetically obese mice with type 2 diabetes promotes eNOS depletion and endothelial dysfunction, and targeted disruption of CCR10/eNOS interaction improves wound healing.
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http://dx.doi.org/10.2337/db21-1108DOI Listing
July 2022

Linezolid-Induced Pure Red Cell Aplasia: A Case Report.

Infect Drug Resist 2022 20;15:3847-3856. Epub 2022 Jul 20.

Infectious Diseases Department, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, People's Republic of China.

Linezolid (LZD) has been widely used for treating the infections of multidrug-resistant gram-positive organisms. As we know, anemias induced by Linezolid (LZD) are common. However, LZD-induced pure red cell aplasia (PRCA) is very rare. In this paper, we report on a 68-year-old woman with intravascular stent infection who developed PRCA after treatment with LZD. The patient presented to our hospital with a 6-month history of fever after stent implantation for aneurysms in both lower limbs. Bone culture grew methicillin-resistant (MRSH). She received LZD after developing adverse reactions to initial antibiotics. Although her infective symptoms were improved by LZD, progressive thrombocytopenia was observed 23 days after LZD therapy. Her platelets declined to 66*10/L and hemoglobin level was 10.1 g/dL. Thrombocytopenia recovered 12 days after cessation of LZD. LZD was administered again due to recovered fever. 57 days after LZD administration, her hemoglobin level was 4.1 g/dL and reticulocytes were 0.2%. Bone marrow smear revealed active granulocyte proliferation and markedly decreased erythropoiesis with vacuolar degeneration. 12 days after cessation of LZD, her hemoglobin and reticulocyte levels rose to 9.6 g/dL and 5.1%, respectively. LZD was used for the third time as fever and inflammatory markers progressively increased, but Hb was reduced to 6.7g/dL 15 days after LZD therapy. 12 days after cessation of LZD, the hemoglobin level rose to 11.9 g/dL. In summary, we suggest complete blood count and reticulocyte count should be monitored to detect bone marrow suppression during long-term LZD therapy, especially in patients aged over 58 and/or with pre-existing anemia, chronic infections, and renal insufficiency.
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http://dx.doi.org/10.2147/IDR.S362358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309292PMC
July 2022

A Genome-Wide Association Study Coupled With a Transcriptomic Analysis Reveals the Genetic Loci and Candidate Genes Governing the Flowering Time in Alfalfa ( L.).

Front Plant Sci 2022 11;13:913947. Epub 2022 Jul 11.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

The transition to flowering at the right time is very important for adapting to local conditions and maximizing alfalfa yield. However, the understanding of the genetic basis of the alfalfa flowering time remains limited. There are few reliable genes or markers for selection, which hinders progress in genetic research and molecular breeding of this trait in alfalfa. We sequenced 220 alfalfa cultivars and conducted a genome-wide association study (GWAS) involving 875,023 single-nucleotide polymorphisms (SNPs). The phenotypic analysis showed that the breeding status and geographical origin strongly influenced the alfalfa flowering time. Our GWAS revealed 63 loci significantly related to the flowering time. Ninety-five candidate genes were detected at these SNP loci within 40 kb (20 kb up- and downstream). Thirty-six percent of the candidate genes are involved in development and pollen tube growth, indicating that these genes are key genetic mechanisms of alfalfa growth and development. The transcriptomic analysis showed that 1,924, 2,405, and 3,779 differentially expressed genes (DEGs) were upregulated across the three growth stages, while 1,651, 2,613, and 4,730 DEGs were downregulated across the stages. Combining the results of our GWAS and transcriptome analysis, in total, 38 candidate genes (7 differentially expressed during the bud stage, 13 differentially expressed during the initial flowering stage, and 18 differentially expressed during the full flowering stage) were identified. Two SNPs located in the upstream region of the gene (which is involved in isop renoids) were significantly related to flowering. The two significant SNPs within the upstream region of existed as four different haplotypes in this panel. The genes identified in this study represent a series of candidate targets for further research investigating the alfalfa flowering time and could be used for alfalfa molecular breeding.
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http://dx.doi.org/10.3389/fpls.2022.913947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310038PMC
July 2022

DLEU7-AS1 promotes renal cell cancer by silencing the miR-26a-5p/coronin-3 axis.

Clin Kidney J 2022 Aug 28;15(8):1542-1552. Epub 2022 Feb 28.

Department of Urology, Zhongshan Hospital Xiamen University, School of medicine, Xiamen University, Xiamen, Fujian, China.

Long non-coding RNAs (lncRNAs) have been implicated in the progression and development of many types of cancer by interacting with RNA, DNA and proteins, including DLEU7-AS1. However, the function of DLEU7-AS1 in renal cell cancer (RCC) remains unclear. In this study, two prediction algorithms were used to discover the potential target of miR-26a-5p, which was determined to be a tumor suppressor gene, possibly DLEU7-AS1, through the downregulation of coronin-3 in RCC. Thus, we hypothesized that DLEU7-AS1 promotes RCC by silencing the miR-26a-5p/coronin-3 axis. To test our hypothesis, we confirmed that DLEU7-AS1 directly targets miR-26a-5p using the pmirGLO dual-luciferase reporter assay. Next, we observed that DLEU7-AS1 expression was markedly upregulated in RCC samples and inversely correlated with clinical prognosis and miR-26a-5p levels. Knockdown of DLEU7-AS1 significantly suppressed the growth and metastasis of RCC cells and attenuated tumor growth . Interestingly, exogenous expression of coronin-3 or miR-26a-5p inhibitor treatment almost completely rescued the DLEU7-AS1 knockdown-induced inhibitory effects on cell proliferation, migration and invasion. In conclusion, our data demonstrate that DLEU7-AS1 is an oncogene in RCC capable of regulating the growth and metastasis of RCC by silencing the miR-26a-5p/coronin-3 axis, suggesting that DLEU7-AS1 can be employed as a potential therapeutic target and prognostic biomarker for RCC.
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http://dx.doi.org/10.1093/ckj/sfac061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308101PMC
August 2022

A Magnetic Metal Hard Mask on Silicon Substrate for Direct Patterning Ultra-High-Resolution OLED Displays.

Micromachines (Basel) 2022 Jun 25;13(7). Epub 2022 Jun 25.

Center for Micro and Nanoscale Research and Fabrication, Hefei National Laboratory for Physical Science at Microscale, University of Science and Technology of China, Hefei 230026, China.

With the development of virtual reality/augmented reality (VR/AR) display devices, the conventional fine metal mask is limited by the wet etch process, which no longer meets the demand for high pixels per inch (PPI) displays. We deposited a layer of magnetic metal on the silicon substrate by physical vapor deposition (PVD), and then developed a 2-inch, 3175 PPI magnetic metal hard mask on silicon substrate (MMS) through deep silicon etching and other micro-nano processing for patterning Organic Light-Emitting Diodes (OLED) displays, which can achieve smaller pixel size and higher PPI. MMS can not only solve the bottleneck problem of the traditional invar alloy shadow mask with low PPI, but also reduce the bending caused by the deformation of the silicon-based mask due to gravity, so that it achieves high PPI and higher uniformity in OLED displays.
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http://dx.doi.org/10.3390/mi13070997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320614PMC
June 2022

Circ_0049472 regulates the damage of Aβ-induced SK-N-SH and CHP-212 cells by mediating the miR-107/KIF1B axis.

Exp Brain Res 2022 Jul 26. Epub 2022 Jul 26.

Department of Neurology, The Second Affiliated Hospital of Hainan Medical University, No. 48, Baishuitang Road, Longhua District, Haikou City, 570311, Hainan Province, China.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects the life and health of the elderly. Studies have found that circular RNAs (circRNAs) are associated with human diseases, including AD. Hsa_circ_0049472 has been uncovered to be overexpressed in AD, but the role of circ_0049472 remains unclear. AD patients were recruited to collect cerebrospinal fluid (CSF) and serum samples. Amyloid beta (Aβ)-induced SK-N-SH and CHP-212 cells were used as the AD cell models in vitro. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of circ_0049472, microRNA-107 (miR-107) and kinesin family member 1B (KIF1B). Cell counting kit-8 assay tested the cell viability, and flow cytometry measured cell apoptosis. The levels of proliferating cell nuclear antigen (PCNA), BCL2 Associated X (Bax) and kinesin family member 1B (KIF1B) protein were examined by western blot. In addition, the relative inflammatory cytokines (TNF-α, IL-6 and IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). The malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured by relative kits. Dual-luciferase reporter assays and RNA pull-down assay verified the relationship between miR-107 and circ_0049472 or KIF1B. Circ_0049472 and KIF1B were overexpressed in AD patient-derived cerebrospinal fluid (CSF) and serum samples, as well as Aβ-induced SK-N-SH and CHP-212 cells. Silencing circ_0049472 promoted cell proliferation, and inhibited cell apoptosis in Aβ-induced SK-N-SH and CHP-212 cells. MiR-107 was a target of circ_0049472. MiR-107 silencing abolished the cell viability and apoptosis affected by down-regulation of circ_0049472 in Aβ-induced SK-N-SH and CHP-212 cells. Besides, miR-107 targeted KIF1B, and overexpressed KIF1B reverted miR-107 elevation-mediated effects on cell apoptosis, inflammation, and oxidative stress of Aβ-induced SK-N-SH and CHP-212 cells. Circ_0049472 modulated KIF1B by serving as a miR-107 decoy, thereby mediating Aβ-induced neurotoxicity, suggesting that circ_0049472 may be involved in AD pathogenesis.
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http://dx.doi.org/10.1007/s00221-022-06401-yDOI Listing
July 2022

De-sialylation of glycopeptides by acid treatment: enhancing sialic acid removal without reducing the identification.

Anal Methods 2022 Aug 4;14(30):2913-2919. Epub 2022 Aug 4.

College of Life Science, Northwest University, Xi'an, Shaanxi Province 710069, China.

Sialic acid, a common terminal monosaccharide on many glycoconjugates, plays essential roles in many biological processes such as immune responses, pathogen recognition, and cancer development. For various purposes, sialic acids may need to be removed from glycopeptides or glycans, mainly using enzymatical or chemical approaches. In this study, we found that most commonly used chemical methods couldn't completely remove sialic acids from glycopeptides. Although the de-sialylation efficiency could be further enhanced by increasing the treatment time or acid concentration, the undesirable side reactions on the peptide portion would decrease glycopeptide identification. By adding the deamidation on carbamidomethyl-cysteine (C), asparagine (N), and glutamine (Q) residues as a variable modification during database search, most of the unidentified spectra could be recovered. This optional acid-treatment and database search method for the complete removal of sialic acids without losing much spectral identification should be quite useful for many glycomic and glycoproteomic studies.
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http://dx.doi.org/10.1039/d2ay00949hDOI Listing
August 2022

Analysis of the metabolites in green tea during roasting process using non-targeted metabolomics.

J Sci Food Agric 2022 Jul 24. Epub 2022 Jul 24.

Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou, China.

Background: Roasting plays an important role in the formation of flavor of roasted green tea; however, the changes in chemicals during this process have not been systematically studied until now. To reveal the dynamic changes in chemicals in green tea during roasting, non-targeted metabolomics, coupled with chemometrics, was employed.

Results: A total of 101 non-volatile metabolites were identified in tea samples, and 29 metabolites were identified as characteristic metabolites of roasting. A significant increase in catechins and their derivatives, organic acids, and flavonoid glycosides was observed, while the content of some amino acids and their derivatives decreased over 50% during roasting. The content of theanine glucoside increased dramatically (by 21.23-fold at the roasting stage), and Maillard-derived compounds also increased to varying degrees.

Conclusion: Glycosylation, oxidative polymerization, and pyrolysis were important reactions responsible for the formation and transformation of flavor compounds in roasted green tea during roasting. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jsfa.12133DOI Listing
July 2022

Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation.

Nat Commun 2022 Jul 22;13(1):4241. Epub 2022 Jul 22.

Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.

Sclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin's protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in ApoE mice and hSOST.ApoE mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOST mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation.
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http://dx.doi.org/10.1038/s41467-022-31997-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307627PMC
July 2022

Mechanism of gelation in high nickel content cathode slurries for sodium-ion batteries.

J Colloid Interface Sci 2022 Jul 8;627:427-437. Epub 2022 Jul 8.

School of Metallurgy and Materials, University of Birmingham, B15 2TT, United Kingdom. Electronic address:

Sodium-ion batteries are a prospective sustainable alternative to the ubiquitous lithium-ion batteries due to the abundancy of sodium, and their cobalt free cathodes. The high nickel O3-type oxides show promising energy densities, however, a time dependency in the rheological properties of the composite electrode slurries is observed, which leads to inhomogeneous coatings being produced. A combination of electron microscopy and infra-red spectroscopy were used to monitor the O3-oxide surface changes upon exposure to air, and the effect upon the rheology and stability of the inks was investigated. Upon exposure to air, NaOH rather than NaCO was observed on the surfaces of the powder through FTIR and EDS. The subsequent gelation of the slurry was initiated by the NaOH and dehydrofluorination with crosslinking of PVDF was observed through the reaction product, NaF. Approximately 15% of the CF bonds in PVDF undergo this dehydrofluorination to form NaF. As observed in the relaxation time of fitted rheological data, the gelation undergoes a three-stage process: a dehydrofluorination stage, creating saturated structures, a crosslinking stage, resulting in the highest rate of gelation, and a final crosslinking stage. This work shows the mechanism for instability of high nickel containing powders and electrode slurries, and presents a new time dependent oscillatory rheology test that can be used to determine the process window for these unstable slurry systems.
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http://dx.doi.org/10.1016/j.jcis.2022.07.033DOI Listing
July 2022

Relationship between High Blood Pressure, Atrial Cardiopathy, and Mortality in the General Population.

Am J Hypertens 2022 Jul 21. Epub 2022 Jul 21.

Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Atrial cardiopathy is associated with increased risk of mortality. However, it is unclear whether this association is modified by hypertension, a risk factor for both atrial cardiopathy and mortality.

Methods: This analysis included 8,023 participants from the Third National Health and Nutrition Examination Survey. Electrocardiographic deep terminal negativity of P-wave in V1 ≥100 µv defined atrial cardiopathy. National Death Index was used to identify date and cause of death. Cox proportional hazard analysis was used to examine the association of atrial cardiopathy with mortality among participants stratified by hypertension status.

Results: 2.7% of the participants had atrial cardiopathy. Over a median follow-up of 14 years, 2,922 all-cause deaths occurred, of which 1,058 were CVD. All-cause death rates were almost double among participants with concomitant atrial cardiopathy and elevated blood pressure (BP) (120-129/<80), stage 1(130-139/80-89) or stage 2 hypertension (≥140/≥90) compared to their counterparts in the same hypertension stages without atrial cardiopathy (47.8, 61.3, and 80.2 vs. 23, 24.7, and 44.8 per 1000 PY, respectively). In multivariable-adjusted models, stronger association between atrial cardiopathy and all-cause mortality was observed in the presence compared to the absence of hypertension (HR 95% CI):1.59(1.25-2.01) vs. 0.67(0.41-1.10), respectively, interaction p-value=0.009). Similarly, an association between atrial cardiopathy and cardiovascular disease (CVD) mortality was observed in the presence compared to the absence of hypertension (HR 95% (CI): 1.64 (1.08-2.47) vs. 0.63 (0.20-2.00), respectively, interaction p-value=0.20).

Conclusions: Concomitant presence of high BP and atrial cardiopathy carries higher risk of mortality, and the risk increases with higher BP levels.
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http://dx.doi.org/10.1093/ajh/hpac087DOI Listing
July 2022

cis-Regulatory variation affecting gene expression contributes to the improvement of maize kernel size.

Plant J 2022 Jul 21. Epub 2022 Jul 21.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

cis-Regulatory variations contribute to trait evolution and adaptation during crop domestication and improvement. As the most important harvested organ in maize (Zea mays L.), kernel size has undergone intensive selection for size. However, the associations between maize kernel size and cis-regulatory variations remain unclear. We chose two independent association populations to dissect the genetic architecture of maize kernel size together with transcriptomic and genotypic data. The resulting phenotypes reflected a strong influence of population structure on kernel size. Compared with genome-wide association studies (GWASs), which accounted for population structure and relatedness, GWAS based on a naïve or simple linear model revealed additional associated single-nucleotide polymorphisms significantly involved in the conserved pathways controlling seed size in plants. Regulation analyses through expression quantitative trait locus mapping revealed that cis-regulatory variations likely control kernel size by fine-tuning the expression of proximal genes, among which ZmKL1 (GRMZM2G098305) was transgenically validated. We also proved that the pyramiding of the favorable cis-regulatory variations has contributed to the improvement of maize kernel size. Collectively, our results demonstrate that cis-regulatory variations, together with their regulatory genes, provide excellent targets for future maize improvement.
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http://dx.doi.org/10.1111/tpj.15910DOI Listing
July 2022

Identifying Novel Clusters of Patients With Prolonged Mechanical Ventilation Using Trajectories of Rapid Shallow Breathing Index.

Front Med (Lausanne) 2022 4;9:880896. Epub 2022 Jul 4.

Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Objective: Patients with prolonged mechanical ventilation (PMV) are comprised of a heterogeneous population, creating great challenges for clinical management and study design. The study aimed to identify subclusters of PMV patients based on trajectories of rapid shallow breathing index (RSBI), and to develop a machine learning model to predict the cluster membership based on baseline variables.

Methods: This was a retrospective cohort study conducted in respiratory care center (RCC) at a tertiary academic medical center. The RCC referral criteria were patients with mechanical ventilation for at least 21 days with stable hemodynamic and oxygenation status. Patients admitted to the RCC from April 2009 to December 2020 were screened. Two-step clustering through linear regression modeling and k-means was employed to find clusters of the trajectories of RSBI. The number of clusters was chosen by statistical metrics and domain expertise. A gradient boosting machine (GBM) was trained, exploiting variables on RCC admission, to predict cluster membership.

Results: A total of 1371 subjects were included in the study. Four clusters were identified: cluster A showed persistently high RSBI; cluster B was characterized by a constant low RSBI over time; Cluster C was characterized by increasing RSBI; and cluster D showed a declining RSBI. Cluster A showed the highest mortality rate (72%), followed by cluster D (63%), C (62%) and B (61%; p = 0.005 for comparison between 4 clusters). GBM was able to predict cluster membership with an accuracy of > 0.95 in ten-fold cross validation. Highly ranked variables for the prediction of clusters included thyroid-stimulating hormone (TSH), cortisol, platelet, free thyroxine (T4) and serum magnesium.

Conclusions: Patients with PMV are composed of a heterogeneous population that can be classified into four clusters by using trajectories of RSBI. These clusters can be easily predicted with baseline clinical variables.
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http://dx.doi.org/10.3389/fmed.2022.880896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289367PMC
July 2022
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