Publications by authors named "Lan Jiang"

439 Publications

Outcomes of coronavirus disease-2019 among veterans with pre-existing diagnosis of heart failure.

ESC Heart Fail 2021 Mar 16. Epub 2021 Mar 16.

Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA.

Aims: Pre-existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease-2019 (COVID-19) outcomes. However, data on outcomes of COVID-19 among people with pre-existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre-existing HF with COVID-19 outcomes.

Methods And Results: A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID-19 diagnosis among Veterans with and without pre-existing diagnosis of HF. Cox-regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID-19, 6148 had pre-existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID-19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61-2.17) and 1.79 (1.66-1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15-1.64) and 1.27 (1.16-1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants.

Conclusions: Patients with COVID-19 and pre-existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin-converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.
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http://dx.doi.org/10.1002/ehf2.13291DOI Listing
March 2021

Functionalization of freeform curved surfaces by shaped femtosecond laser pulses in the propagation axis.

Opt Express 2021 Feb;29(4):5487-5496

With ultrashort pulse durations and ultrahigh peak intensities, ultrafast lasers can create different types of micro/nano-structures to functionalize the processed surface with new properties. However, the applications of this method on freeform surfaces are still limited by the short length of a laser focusing spot and complex control of the 3D moving trajectory in the fabrication process. In this paper, we overcome this problem by shaping the on-axis intensity along the propagation axis using the spatial light modulator. By designing the phase mask, we increased the length of the stable-intensity zone (intensity fluctuation < 10%) by more than 3 times compared to that of an unshaped Bessel beam. The energy deposition was also optimized to be less than 2% fluctuation based on simulations. Using this method, we fabricated micro/nano structures on 3D surfaces at different fluences and demonstrated various properties including colorization, anti-reflection, and hydrophobicity in large height range. We demonstrated the applications of the proposed method in creating hydrophobicity on complex freeform syringe tip surfaces. This improved the minimum manipulatable volume of a liquid droplet to 2 times smaller compared with untreated syringe, thus greatly extending its performance for micro-droplet manipulation. This method offers an alternative approach for reliable and affordable freeform curved-surface processing.
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http://dx.doi.org/10.1364/OE.418663DOI Listing
February 2021

Delirium and Functional Recovery in Patients Discharged to Skilled Nursing Facilities After Hospitalization for Heart Failure.

JAMA Netw Open 2021 Mar 1;4(3):e2037968. Epub 2021 Mar 1.

Providence VA Medical Center, Center of Innovation in Long Term Services and Supports, Providence, Rhode Island.

Importance: A substantial number of patients discharged to skilled nursing facilities (SNFs) after heart failure (HF) hospitalization experience regression in function or do not improve. Delirium is one of few modifiable risk factors in this patient population. Therefore, understanding the role of delirium in functional recovery may be useful for improving outcomes.

Objective: To assess the association of delirium with 30-day functional improvement in patients discharged to SNFs after HF hospitalization.

Design, Setting, And Participants: This retrospective cohort study included patients hospitalized for HF in 129 US Department of Veterans Affairs hospitals who were discharged to SNFs from October 1, 2010, to September 30, 2015. Data were analyzed from June 14 to December 18, 2020.

Exposures: Delirium, as determined by the Minimum Data Set (MDS) 3.0 Confusion Assessment Method, with dementia as a covariate, determined via International Classification of Diseases, Ninth Revision (ICD-9) coding.

Main Outcomes And Measures: The difference between admission and 30-day MDS 3.0 Activities of Daily Living (ADL) scores.

Results: A total of 20 495 patients (mean [SD] age, 78 [10.3] years; 78.9% White; and 97% male) were included in the analysis. Of the total sample, 882 patients (4.3%) had delirium on an SNF admission. The mean (SD) baseline ADL score on admission to SNF was significantly worse among patients with delirium than without (18.3 [4.7] vs 16.1 [5.2]; P < .001; d = 0.44.). On the 30-day repeated assessment, mean (SD) function (ADL scores) improved for both patients with delirium (0.6 [2.9]) and without delirium (1.8 [3.6]) (P < .001; d = -0.38). In the multivariate adjusted model, delirium was associated with statistically significant lower ADL improvement (difference in ADL score, -1.07; 95% CI, -1.31 to -0.83; P < .001).

Conclusions And Relevance: In this retrospective cohort study, patients with HF discharged to SNFs with delirium were less likely to show improvement in function compared with patients without delirium. Findings suggest a potential need to reexamine how and when health care professionals assess delirium in HF patients throughout their hospitalization and SNF course. Identifying and treating delirium for HF patients earlier in their care trajectory may play an important role in improving care and long-term functional outcomes in this population. Future research is warranted to further investigate the association between delirium and functional recovery for HF and other patient populations.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.37968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967078PMC
March 2021

Preparation of dextran-casein phosphopeptide conjugates, evaluation of its calcium binding capacity and digestion in vitro.

Food Chem 2021 Aug 20;352:129332. Epub 2021 Feb 20.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, No. 29, No. 13 Ave., TEDA, Tianjin 300457, China. Electronic address:

In order to construct a novel and efficient calcium delivery system, a dextran- casein phosphopeptide (CPP) conjugates as calcium carrier was prepared by Maillard reaction of CPP and dextran. The preparation of the conjugates, construction of calcium delivery system and digestion in vitro were studied. The grafting rate of conjugates, which was confirmed by migration and intensity changes in the characteristic peaks using ultraviolet-visible and Fourier transform infrared spectroscopy, reached 48.88%. The microscopy showed CPP was coated with dextran, the conjugates with a kind of "shell-core" structure had excellent stability. Compared with CPP, the chelating rate of conjugates increased from 6.0% to 13.87%, and the calcium retention rate improved from 1.09% to 7.90% in vitro digestion. The calcium binding capacity and effect of controlled release of the conjugates were superior to those of CPP. Therefore, the conjugates could be used as an effective carrier for new calcium supplements.
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http://dx.doi.org/10.1016/j.foodchem.2021.129332DOI Listing
August 2021

The progress in research: ALS/FTD pathogenesis, functions and structure.

Small GTPases 2021 Mar 5:1-21. Epub 2021 Mar 5.

Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, College of Life Sciences, Sichuan University, Chengdu, China.

The hexanucleotide repeat (GGGGCC) expansion in is accounted for a large proportion of the genetic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The hypotheses of how the massive G4C2 repeats in destroy the neurons and lead to ALS/FTD are raised and improving. As a multirole player, C9orf72 exerts critical roles in many cellular processes, including autophagy, membrane trafficking, immune response, and so on. Notably, the partners of C9orf72, through which C9orf72 participates in the cell activities, have been identified. Notably, the structures of the C9orf72-SMCR8-WDR41 complex shed light on its activity as GTPase activating proteins (GAP). In this manuscript, we reviewed the latest research progress in the C9orf72-mediated ALS/FTD, the physiological functions of C9orf72, and the putative function models of C9orf72/C9orf72-containing complex.
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http://dx.doi.org/10.1080/21541248.2021.1892443DOI Listing
March 2021

Summary of the Experience in the Diagnosis and Treatment of Complex Preauricular Fistulas in 78 Children.

Front Surg 2020 1;7:609852. Epub 2021 Feb 1.

Department of Otorhinolaryngology Head and Neck Surgery Henan Children's Hospital, Department of Otorhinolaryngology Head and Neck Surgery, Zhengzhou Children's Hospital, Zhengzhou, China.

This study aimed to investigate the application of mini-incisions in complex preauricular fistula resection in children. A total of 78 children who were diagnosed with preauricular fistula infection between January 2017 and December 2019 were included in the study. Their clinical data were analyzed retrospectively, and surgical treatment with mini-incisions based on plastic surgery principles and techniques was provided. All the patients achieved healing following the first application of the treatment. The patients were followed up for 6-42 months, and no recurrence or local auricular deformation occurred. The application of mini-incisions and plastic surgery techniques in complex preauricular fistula resection in children can achieve a good effect and improve the satisfaction of the children and their parents.
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http://dx.doi.org/10.3389/fsurg.2020.609852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882734PMC
February 2021

Deciphering the roles of leucine-rich repeat receptor-like protein kinases (LRR-RLKs) in response to Fusarium wilt in the Vernicia fordii (Tung tree).

Phytochemistry 2021 May 12;185:112686. Epub 2021 Feb 12.

Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China; Key Lab of Non-wood Forest Products of State Forestry Administration, College of Forestry, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China. Electronic address:

Leucine-rich repeat receptor-like protein kinases (LRR-RLKs) are vital for plant growth and development, signal transduction, immunity, and play diverse roles in plant defense responses. However, the LRR-RLK genes have not been systematically studied in Vernicia fordii (tung tree), especially its response to Fusarium wilt. Here, we carried out an integrative analysis of LRR-RLKs among five Euphorbiaceae species: Hevea brasiliensis (rubber tree), Manihot esculenta (cassava), Jatropha curcas (physic nut), Ricinus communis (castor bean), and V. fordii, which contained 223, 311, 186, 138, and 167 LRR-RLKs, respectively. Maximum-likelihood tree was estimated using LRR-RLKs of Arabidopsis thaliana as a template, and they allowed us to divide Euphorbiaceae LRR-RLKs into 22 groups. There are 126 segmental and 30 tandem duplications in these Euphorbiaceae genomes by synteny analysis. The tissue-specific expression patterns revealed that V. fordii LRR-RLKs (VfLRR-RLKs) were differentially expressed in various tissues, and some of them exhibited specific expression in meristems tissues, which suggested their potential functions during organ formation and cell fate specification. Two VfLRR-RLK pairs (Vf01G2125 and Vf03G1740, Vf06G2687 and Vf10G1659), which generated by tandem duplication events, were associated with possible resistance to Fusarium wilt infection. The qRT-PCR confirmed these four VfLRR-RLKs contained opposite expression profiles during pathogen infection in V. fordii and V. montana. Taken together, our data systematically analyzed the LRR-RLK family in Euphorbiaceae genomes for the first time. We highlight the putative roles of VfLRR-RLKs in response to Fusarium wilt infection, and VfLRR-RLKs may be further applied in marker-assisted breeding to control Fusarium wilt in V. fordii.
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http://dx.doi.org/10.1016/j.phytochem.2021.112686DOI Listing
May 2021

One-Step Fabrication Method of GaN Films for Internal Quantum Efficiency Enhancement and Their Ultrafast Mechanism Investigation.

ACS Appl Mater Interfaces 2021 Feb 8;13(6):7688-7697. Epub 2021 Feb 8.

Laser Assisted Nano Engineering Laboratory, Department of Electrical Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0511, United States.

The third-generation semiconductors are the cornerstone of the power semiconductor leap forward and have attracted much attention because of their excellent properties and wide applications. Meanwhile, femtosecond laser processing as a convenient method further improves the performance of the related devices and expands the application prospect. In this work, an approximate 3 times improvement of the internal quantum efficiency (IQE) and a 5.5 times enhancement of the photoluminescence (PL) intensity were achieved in the GaN film prepared using a one-step femtosecond laser fabrication method. Three types of final micro/nanostructures were found with different femtosecond laser fluences, which could be attributed to the decomposition, melting, bubble nucleation, and phase explosion of GaN. The mechanisms of the microbump structure formation and enhancement of IQE were studied experimentally by the time-resolved reflection pump-probe technique, X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Simulations for the laser-GaN interaction have also been performed to ascertain the micro/nanostructure formation principle. These results promote the potential applications of femtosecond lasers on GaN and other wide band gap semiconductors, such as UV-light-emitting diodes (LEDs), photodetectors, and random lasers for use in sensing and full-field imaging.
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http://dx.doi.org/10.1021/acsami.0c19726DOI Listing
February 2021

COVID-19 and Public Interest in Ophthalmic Services and Conditions.

R I Med J (2013) 2021 Feb 1;104(1):61-64. Epub 2021 Feb 1.

Division of Ophthalmology, Alpert Medical School, Brown University; Section of Ophthalmology, Providence VA Medical Center, Providence, Rhode Island; Office of Academic Affiliations, US Department of Veterans Affairs, Washington DC.

Objective: To assess the impact of the COVID-19 pandemic and associated lockdowns on public interest in ophthalmology.

Methods: Search interest data for ophthalmic services and conditions were collected from January 1, 2019 to June 21, 2020. Temporal statistical analysis was used to identify significant trends. Weekly data on ophthalmic services and conditions search interest obtained from Google Trends were analyzed with analysis of variance testing and the generalized linear model based on dates.

Results: Ophthalmic services searches decreased after the first COVID-19 case in the country (p<0.001); ophthalmic services and conditions search interest also declined after the first COVID-19 case and lockdown orders in each state (p<0.001). Following the first in-state COVID-19 case, search interest in ophthalmic services fell more than for ophthalmic conditions (p=0.0088). Lockdown and COVID-19 had similar effects on ophthalmic services search interest (p=0.2246), but interest in ophthalmic conditions decreased more after lockdown than after the first in-state case (p<0.0001).

Conclusions: Most of the decrease in search interest in ophthalmic services was associated with COVID-19 rather than lockdown orders, suggesting that public interest in ophthalmic care may be more sensitive to changes in the COVID-19 pandemic than lockdown orders.
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February 2021

Microprocessing on Single Protein Crystals Using Femtosecond Pulse Laser.

ACS Biomater Sci Eng 2020 11 23;6(11):6445-6452. Epub 2020 Sep 23.

School of Life Sciences, Tsinghua University, Beijing 100084, China.

Proteins with different micropatterns have various applications in biosensing, structural analysis, and other biomedical fields. However, processing of micropatterns on single protein crystals remains a challenge due to the fragility of protein molecules. In this work, we studied femtosecond laser processing on single hen egg white lysozyme protein crystals. Optimized laser parameters were found to achieve micropatterning without cracking of protein crystals. The ablation morphology dependence on the laser fluence and the pulse number was discussed to control the processing results. Under a laser fluence higher than 1 J/cm, the ablation hole was formed. While multipulses with fluence lower than the ablation threshold were applied, the foaming area was observed due to the denaturation of protein. The numerical simulation shows that the ablation results were influenced by the ionization and energy deposition process. Micropatterns including lines, areas, and microarrays can be processed with a minimum size of 2 μm. Processed patterns on the crystal surface can be used for biosensing microarrays and the enhancement of crystal growth. The microprocessing method proposed in this study has potential applications in different fields including biodevices and biomedicine.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01023DOI Listing
November 2020

Association of Genetic Variation With Cirrhosis: A Multi-Trait Genome-Wide Association and Gene-Environment Interaction Study.

Gastroenterology 2021 Apr 11;160(5):1620-1633.e13. Epub 2020 Dec 11.

Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background & Aims: In contrast to most other common diseases, few genetic variants have been identified that impact risk of cirrhosis. We aimed to identify new genetic variants that predispose to cirrhosis, to test whether such variants, aggregated into a polygenic score, enable genomic risk stratification, and to test whether alcohol intake or body mass index interacts with polygenic predisposition.

Methods: We conducted a multi-trait genome-wide association study combining cirrhosis and alanine aminotransferase levels performed in 5 discovery studies (UK Biobank, Vanderbilt BioVU, Atherosclerosis Risk in Communities study, and 2 case-control studies including 4829 individuals with cirrhosis and 72,705 controls and 362,539 individuals with alanine aminotransferase levels). Identified variants were replicated in 3 studies (Partners HealthCare Biobank, FinnGen, and Biobank Japan including 3554 individuals with cirrhosis and 343,826 controls). A polygenic score was tested in Partners HealthCare Biobank.

Results: Five previously reported and 7 newly identified genetic variants were associated with cirrhosis in both the discovery studies multi-trait genome-wide association study (P < 5 × 10) and the replication studies (P < .05), including a missense variant in the APOE gene and a noncoding variant near EFN1A. These 12 variants were used to generate a polygenic score. Among Partners HealthCare Biobank individuals, high polygenic score-defined as the top quintile of the distribution-was associated with significantly increased risk of cirrhosis (odds ratio, 2.26; P < .001) and related comorbidities compared with the lowest quintile. Risk was even more pronounced among those with extreme polygenic risk (top 1% of the distribution, odds ratio, 3.16; P < .001). The impact of extreme polygenic risk was substantially more pronounced in those with elevated alcohol consumption or body mass index. Modeled as risk by age 75 years, probability of cirrhosis with extreme polygenic risk was 13.7%, 20.1%, and 48.2% among individuals with no or modest, moderate, and increased alcohol consumption, respectively (P < .001). Similarly, probability among those with extreme polygenic risk was 6.5%, 10.3%, and 19.5% among individuals with normal weight, overweight, and obesity, respectively (P < .001).

Conclusions: Twelve independent genetic variants, 7 of which are newly identified in this study, conferred risk for cirrhosis. Aggregated into a polygenic score, these variants identified a subset of the population at substantially increased risk who are most susceptible to the hepatotoxic effects of excess alcohol consumption or obesity.
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http://dx.doi.org/10.1053/j.gastro.2020.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035329PMC
April 2021

Laser photonic-reduction stamping for graphene-based micro-supercapacitors ultrafast fabrication.

Nat Commun 2020 Dec 3;11(1):6185. Epub 2020 Dec 3.

Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.

Micro-supercapacitors are promising miniaturized energy storage devices that have attracted considerable research interest. However, their widespread use is limited by inefficient microfabrication technologies and their low energy density. Here, a flexible, designable micro-supercapacitor can be fabricated by a single pulse laser photonic-reduction stamping. A thousand spatially shaped laser pulses can be generated in one second, and over 30,000 micro-supercapacitors are produced within 10 minutes. The micro-supercapacitor and narrow gaps were dozens of microns and 500 nm, respectively. With the unique three-dimensional structure of laser-induced graphene based electrode, a single micro-supercapacitor exhibits an ultra-high energy density (0.23 Wh cm), an ultra-small time constant (0.01 ms), outstanding specific capacitance (128 mF cm and 426.7 F cm) and a long-term cyclability. The unique technique is desirable for a broad range of applications, which surmounts current limitations of high-throughput fabrication and low energy density of micro-supercapacitors.
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http://dx.doi.org/10.1038/s41467-020-19985-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712890PMC
December 2020

Evaluation of Changes in Veterans Affairs Medical Centers' Mortality Rates After Risk Adjustment for Socioeconomic Status.

JAMA Netw Open 2020 12 1;3(12):e2024345. Epub 2020 Dec 1.

Center of Innovation for Long-term Services and Supports, Providence Veterans Affairs Medical Center, Providence, Rhode Island.

Importance: Socioeconomic factors are associated with worse outcomes after hospitalization, but neither the Centers for Medicare & Medicaid Services (CMS) nor the Veterans Affairs (VA) health care system adjust for socioeconomic factors in profiling hospital mortality.

Objective: To evaluate changes in Veterans Affairs medical centers' (VAMCs') risk-standardized mortality rates among veterans hospitalized for heart failure and pneumonia after adjusting for socioeconomic factors.

Design, Setting, And Participants: In this cross-sectional study, retrospective data were used to assess 131 VAMCs' risk-standardized 30-day mortality rates with or without adjustment for socioeconomic covariates. The study population included 42 892 veterans hospitalized with heart failure and 39 062 veterans hospitalized with pneumonia from January 1, 2012, to December 31, 2014. Data were analyzed from March 1, 2019, to April 1, 2020.

Main Outcomes And Measures: The primary outcome was 30-day mortality after admission. Socioeconomic covariates included neighborhood disadvantage, race/ethnicity, homelessness, rurality, nursing home residence, reason for Medicare eligibility, Medicaid and Medicare dual eligibility, and VA priority.

Results: The study population included 42 892 veterans hospitalized with heart failure (98.2% male; mean [SD] age, 71.9 [11.4] years) and 39 062 veterans hospitalized with pneumonia (96.8% male; mean [SD] age, 71.0 [12.4] years). The addition of socioeconomic factors to the CMS models modestly increased the C statistic from 0.77 (95% CI, 0.77-0.78) to 0.78 (95% CI, 0.78-0.78) for 30-day mortality after heart failure and from 0.73 (95% CI, 0.72-0.73) to 0.74 (95% CI, 0.73-0.74) for 30-day mortality after pneumonia. Mortality rates were highly correlated (Spearman correlations of ≥0.98) in models that included or did not include socioeconomic factors. With the use of the CMS model for heart failure, VAMCs in the lowest quintile had a mean (SD) mortality rate of 6.0% (0.4%), those in the middle 3 quintiles had a mean (SD) mortality rate of 7.2% (0.4%), and those in the highest quintile had a mean (SD) mortality rate of 8.8% (0.6%). After the inclusion of socioeconomic covariates, the adjusted mean (SD) mortality was 6.1% (0.4%) for hospitals in the lowest quintile, 7.2% (0.4%) for those in the middle 3 quintiles, and 8.6% (0.5%) for those in the highest quintile. The mean absolute change in rank after socioeconomic adjustment was 3.0 ranking positions (interquartile range, 1.0-4.0) among hospitals in the highest quintile of mortality after heart failure and 4.4 ranking positions (interquartile range, 1.0-6.0) among VAMCs in the lowest quintile. Similar findings were observed for mortality rankings in pneumonia and after inclusion of clinical covariates.

Conclusions And Relevance: This study suggests that adjustments for socioeconomic factors did not meaningfully change VAMCs' risk-adjusted 30-day mortality rates for veterans hospitalized for heart failure and pneumonia. The implications of such adjustments should be examined for other quality measures and health systems.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.24345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716194PMC
December 2020

The role of lipoprotein-associated phospholipase A2 in acute kidney injury of septic mice.

Transl Androl Urol 2020 Oct;9(5):2192-2199

Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Background: This experiment aimed to investigate the role and mechanism of lipoprotein-associated phospholipase A2 (Lp-PLA2) in kidney injury in septic mice induced by cecal ligation and perforation (CLP).

Methods: Male BALB/c mice were randomly divided into two groups: sham-operation group (Sham group) and septic group (CLP group). The septic model was simulated by cecal ligation and puncture method, but only cecal ligation was used for the sham operation group. The whole serum and renal tissue samples of the mice were collected 24 hours after modeling in both groups. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of renal tissue, the renal injury score was recorded, and the creatinine (Cr) and blood urea nitrogen (BUN) levels were detected by automatic biochemical analyzer, while the serum Lp-PLA2 level was detected by enzyme-linked immunosorbent assay (ELISA). The 7-day survival rate and the survival curve of the two groups were statistically analyzed.

Results: Compared with the Sham group, the pathological score of renal injury in the CLP Group was higher, the level of Lp-PLA2 in serum was significantly increased (all P<0.01), and the expression of Lp-PLA2 in renal tissue was significantly elevated (all P<0.01). Furthermore, the 7-day survival rate of the Sham group was 90%, while that of CLP group was 25%.

Conclusions: The expression level of Lp-PLA2 in blood and kidney tissue of septic mice was increased and correlated with prognosis. However, the predictive value of Lp-PLA2 for prognosis in septic mice needs further study.
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http://dx.doi.org/10.21037/tau-20-1173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658152PMC
October 2020

Bioinformatics Analysis Discovers Microtubular Tubulin Beta 6 Class V (TUBB6) as a Potential Therapeutic Target in Glioblastoma.

Front Genet 2020 18;11:566579. Epub 2020 Sep 18.

Central Laboratory, Yijishan Hospital of Wannan Medical College, Wuhu, China.

Glioblastoma (GBM) has long been a major clinical research challenge to scientists. The pivotal role of the mitochondria related gene family in the promotion of GBM tumorigenesis is not clear. We detected that microtubular tubulin beta 6 class V (TUBB6) was one of 33 differentially expressed mitochondrial-focused genes (DEMFGs) in GBM, and considered that TUBB6 is a potential therapeutic target in GBM. TUBB6 was vital for GBM and marked as the key prognostic gene in primary GBM. Mutations of TUBB6 in GBM were rare. Only four TUBB6 co-expressed hub genes (ANXA2, S100A11, FLNA, and MSN) exhibited poorer overall survival rates in higher expression groups (-value < 0.05). We have confirmed the up-regulation of TUBB6 and its partners, ANXA2 and S100A11 in GBM and validated their importance as prognostic factors in primary GBM. TUBB6 was significantly correlated with stromal score in GBM samples (-value = 6.99E-04). This study aimed to assess the importance of novel hub genes by analyzing the expression, potential function and prognostic impact of TUBB6 in human primary GBM cancer.
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http://dx.doi.org/10.3389/fgene.2020.566579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531581PMC
September 2020

Generation of Fluorinated Amychelin Siderophores against Pseudomonas aeruginosa Infections by a Combination of Genome Mining and Mutasynthesis.

Cell Chem Biol 2020 12 12;27(12):1532-1543.e6. Epub 2020 Nov 12.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. Electronic address:

Pioneering microbial genomic surveys have revealed numerous untapped biosynthetic gene clusters, unveiling the great potential of new natural products. Here, using a combination of genome mining, mutasynthesis, and activity screening in an infection model comprising Caenorhabditis elegans and Pseudomonas aeruginosa, we identified candidate virulence-blocking amychelin siderophore compounds from actinomycetes. Subsequently, we developed unreported analogs of these virulence-blocking siderophores with improved potency by exploiting an Amycolatopsis methanolica strain 239 chorismate to salicylate a biosynthetic subpathway for mutasynthesis. This allowed us to generate the fluorinated amychelin, fluoroamychelin I, which rescued C. elegans from P. aeruginosa-mediated killing with an EC value of 1.4 μM, outperforming traditional antibiotics including ceftazidime and meropenem. In general, this paper describes an efficient platform for the identification and production of classes of anti-microbial compounds with potential unique modes of action.
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http://dx.doi.org/10.1016/j.chembiol.2020.10.009DOI Listing
December 2020

The role of protein kinase C alpha in tri-ortho-cresyl phosphate-induced autophagy in human neuroblastoma SK-N-SH cells.

J Appl Toxicol 2020 11 6;40(11):1480-1490. Epub 2020 Jul 6.

School of Public Health, University of South China, Hengyang, China.

As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate-induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKCα) signaling in neuroblastoma SK-N-SH cells. PKCα activators could positively regulate TOCP-induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKCα activation impaired the ubiquitin-proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF-H families in neurodegenerative disorders.
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http://dx.doi.org/10.1002/jat.3999DOI Listing
November 2020

RIP mutated ITS genes in populations of and their implications for molecular systematics.

IMA Fungus 2020 16;11:18. Epub 2020 Sep 16.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101 China.

Different hypotheses have been proposed to interpret the observed unusual ITS (internal transcribed spacer) sequences in . The coexistence of diverged ITS paralogs in a single genome was previously shown by amplifying the ITS region from mono-ascospore isolates using specific primers designed for different ITS paralog groups. Among those paralogs, are AT-biased ITS sequences which were hypothesized to result from repeat-induced point mutation (RIP). This is a process that detects and mutates repetitive DNA and frequently leads to epigenetic silencing, and these mutations have been interpreted as pseudogenes. Here we investigate the occurrence and frequency of ITS pseudogenes in populations of using large-scale sampling, and discusses the implications of ITS pseudogenes for fungal phylogenetic and evolutionary studies. Our results demonstrate a wide distribution of ITS pseudogenes amongst different geographic populations, and indicate how ITS pseudogenes can contribute to the reconstruction of the evolutionary history of the species.
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http://dx.doi.org/10.1186/s43008-020-00040-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493409PMC
September 2020

Omega-3 fatty acids plus vitamin for women with gestational diabetes or prediabetes: a meta-analysis of randomized controlled studies.

J Matern Fetal Neonatal Med 2020 Sep 23:1-8. Epub 2020 Sep 23.

Department of Emergency medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China.

Introduction: Omega-3 fatty acids plus vitamin (e.g. vitamin D and E) may be beneficial to treat gestational diabetes mellitus (GDM), and we aimed to study the influence of omega-3 fatty acids plus vitamin versus placebo on the treatment efficacy of GDM.

Methods: We searched the databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials, and randomized controlled trials (RCTs) assessing the influence of omega-3 fatty acids and vitamins combination supplementation versus placebo on metabolic status of GDM were included.

Results: Five RCTs were included in the meta-analysis. Compared with control intervention for women with GDM or prediabetes, omega-3 fatty acids plus vitamin substantially reduced fasting plasma glucose (FPG, mean difference [MD] = -11.25; 95% confidence intervals [CI] = -13.73 to -8.77;  < .00001), insulin (MD=-6.16; 95% CI=-7.92 to -4.39;  < .00001), homeostasis model of assessment-insulin resistance (HOMA-IR, MD = 173.51; 95% CI = 164.72 to 182.30;  < .00001) and triglycerides (MD = 173.51; 95% CI = 164.72 to 182.30;  < .00001), as well as increased total antioxidant capacity (TAC, MD = 173.51; 95% CI = 164.72 to 182.30;  < .00001), but revealed no significant impact on total cholesterol (MD = 173.51; 95% CI = 164.72 to 182.30;  < .00001), low‑density lipoprotein cholesterol (LDL-C, MD = 173.51; 95% CI = 164.72 to 182.30;  < .00001), preterm delivery (OR = 173.51; 95% CI = 164.72 to 182.30;  < .00001) or macrosomia > 4000 g (OR = 173.51; 95% CI = 164.72 to 182.30;  < .00001).

Conclusions: The supplementation of omega-3 fatty acids in combination with vitamin D or E can improve glycemic control, alleviate oxidative stress, and reduce triglycerides, but had no effects on total cholesterol, preterm delivery or macrosomia > 4000 g in women with GDM or prediabetes.
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http://dx.doi.org/10.1080/14767058.2020.1814239DOI Listing
September 2020

A New Co-Crystal of Synthetic Drug Rosiglitazone with Natural Medicine Berberine: Preparation, Crystal Structures, and Dissolution.

Molecules 2020 Sep 18;25(18). Epub 2020 Sep 18.

Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

A co-crystal of rosiglitazone (Rsg) with berberine (Bbr), Rsg-Bbr, was prepared by the solvent evaporation method and characterized. The results showed that the electrostatic attraction existed between the nitrogen anion of rosiglitazone and the quaternary ammonium cation of berberine, and C-H···O hydrogen bonds were formed between Rsg and Bbr. In the crystal structure, rosiglitazone molecules stack into a supramolecular layer through π-π interactions while π-π interactions between berberine cations also result in a similar layer. The co-crystal presented a low moisture adsorption curve in the range of 0-95% relative humidity values at 25 °C. The improved dissolution rate of rosiglitazone in pH = 6.8 buffer solution could be achieved after forming co-crystal.
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http://dx.doi.org/10.3390/molecules25184288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570454PMC
September 2020

Hidden in plain sight: Systematic investigation of Leucine-rich repeat containing genes unveil the their regulatory network in response to Fusarium wilt in tung tree.

Int J Biol Macromol 2020 Nov 20;163:1759-1767. Epub 2020 Sep 20.

Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha 410004, Hunan, China; Key Lab of Non-wood Forest Products of State Forestry Administration, College of Forestry, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. Electronic address:

Leucine-rich repeat-containing genes (LRRs) have been reported to play important roles in responses to diseases. However, we poorly understood the response of LRRs to Fusarium wilt infection in tung tree (Vernicia fordii), which is an important economic tree. Here, 437 LRR-containing proteins containing nine types of LRR domains were identified in V. fordii genome. Phylogenetic analysis suggested that nine types of LRR domains could not be divided into separate classes, implying that these LRR domains had a common origin. Totally, 27 LRRs were related to possible resistance to Fusarium wilt after 2, 8, and 13 days post-inoculation. We further found that Vf06G1605 was up-regulate under Fusarium wilt infection after these three time points, Vf10G1602 and Vf02G1413 were up-regulated at 8, and 13 dpi, while Vf07G2320 was down-regulated at these three time points. The WGCNA and promoter elements suggested that WRKY possibly regulate the responses of LRRs to Fusarium wilt infection. This study highlighted the phylogeny and function of LRRs in V. fordii and provided a systematic analysis of these genes in the V. fordii genome. Our results presented here might clearly illustrate physiological mechanisms of resistance to Fusarium wilt infection and the target of marker-assisted breeding in V. fordii.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.106DOI Listing
November 2020

Acupuncture Modulates Disrupted Whole-Brain Network after Ischemic Stroke: Evidence Based on Graph Theory Analysis.

Neural Plast 2020 19;2020:8838498. Epub 2020 Aug 19.

Department of Neurology and Stroke Center, Dongzhimen Hospital, The First Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China.

Background: Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive.

Methods: 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency.

Results: Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (), global efficiency (), and the mean local efficiency () of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and . Acupuncture improved the patients' clustering coefficient () and but did not make a significant impact on the and . The postacupuncture variables of the whole-brain network had no association with the time of onset.

Conclusion: The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.
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http://dx.doi.org/10.1155/2020/8838498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453235PMC
August 2020

The correlations between the serum expression of miR-206 and the severity and prognosis of sepsis.

Ann Palliat Med 2020 Sep 3;9(5):3222-3234. Epub 2020 Sep 3.

Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Background: An accurate assessment of the severity and prognosis of sepsis, especially septic shock, is vital for the tailored treatment of this condition. miRNA participates in the inflammatory response and cell apoptosis and regulates inflammation-related signaling pathways. Immune disorders often accompany sepsis. Since serum miRNA expression is superior to traditional biological markers in terms of sensitivity and specificity, its role in the assessment of sepsis has increasingly been recognized.

Methods: Serum miRNAs were extracted from septic patients and healthy individuals by using the ultracentrifugation method. The differential expressions of miRNAs in the serum samples were detected by high-throughput sequencing technology. The differentially expressed miRNAs between the two groups were analyzed by bioinformatics. The quantitative polymerase chain reaction real-time polymerase chain reaction (qRT-PCR) was used to amplify the sample size to verify the results and to screen the highly-expressed miR206 in septic patients. Subsequently, serum samples were collected from 63 septic patients, and 30 patients with septic shock and qRT-PCR were performed to analyze the expression of miR-206. These 93 patients were divided into the miR-206 low-expression group and miR-206 high-expression group according to miR206 expression level. The potential correlations between the miR-206 expression and the clinical data were analyzed by using SPSS 25.0.

Results: Serum miRNA expression significantly differed between septic patients and healthy individuals. High-throughput sequencing results showed that, compared with those in healthy individuals, 29 miRNA molecules were down-regulated, and 25 molecules were up-regulated in the serum samples of septic patients. qRT-PCR identified the significantly up-regulated miR-206 in septic patients. qRT-PCR also showed significantly higher miR-206 expression levels in patients with septic shock than in septic patients. Furthermore, we observed a significantly longer prothrombin time and activated partial thromboplastin time, and significantly higher SOFA score, APACHE-II score, and in-hospital mortality rate. miR-206 was positively correlated with SOFA sore and APACHE-II score.

Conclusions: Serum miR-206 expression is positively correlated with the severity and prognosis of sepsis. Thus, it may be a potential biomarker for assessing the severity and prognosis of sepsis, although the specific mechanism warrants further investigations.
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http://dx.doi.org/10.21037/apm-20-1391DOI Listing
September 2020

Identification and expression profile of microRNA in seven tissues of the Golden snub-nosed monkey (Rhinopithecus roxellanae).

Mol Genet Genomics 2020 Nov 11;295(6):1547-1558. Epub 2020 Sep 11.

Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, 610065, Sichuan, China.

MicroRNAs (miRNAs) are key in the post-transcriptional regulation of gene expression and thus characterization of miRNAs and investigation of the relative abundance and specificity of tissue expression are essential for understanding gene expression in the golden snub-nosed monkey (GSM, Rhinopithecus roxellanae). Here, we report the first dataset of GSM miRNAs where we identified 460 miRNAs in seven tissues, with 246 conserved known mature miRNAs and 214 novel mature miRNAs. We determined miRNA abundance and expression in the seven tissues using a Tissue Specificity Index score and found that most novel GSM miRNAs showed a highly tissue-specific expression pattern. In particular, 67 novel miRNAs and the miR-34 family were expressed in abundance only in the lung. Five known miRNAs were highly abundant in digestive organs such as the pancreas and liver, and four novel miRNAs were highly expressed in the heart and muscle. Annotation of target genes of GSM miRNAs indicated that target genes were enriched in many important pathways, such as the HIF-1 signaling pathway and xenobiotic biodegradation-related pathways. Collectively, these results emphasize that miRNAs play important roles in GSM diet and high-elevation adaptation regulation. In summary, this study provides essential information on GSM miRNAs and will benefit further investigations of the function and mechanism of miRNAs in controlling gene expression in the GSM.
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http://dx.doi.org/10.1007/s00438-020-01720-7DOI Listing
November 2020

Analyzing the lncRNA, miRNA, and mRNA-associated ceRNA networks to reveal potential prognostic biomarkers for glioblastoma multiforme.

Cancer Cell Int 2020 15;20:393. Epub 2020 Aug 15.

Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241001 People's Republic of China.

Background: Glioblastoma multiforme (GBM) is the most seriously brain tumor with extremely poor prognosis. Recent research has demonstrated that competitive endogenous RNA (ceRNA) network which long noncoding RNAs (lncRNAs) act as microRNA (miRNA) sponges to regulate mRNA expression were closely related to tumor development. However, the regulatory mechanisms and functional roles of ceRNA network in the pathogenesis of GBM are remaining poorly understood.

Methods: In this study, we systematically analyzed the expression profiles of lncRNA and mRNA (GSE51146 dataset) and miRNA (GSE65626 dataset) from GEO database. Then, we constructed a ceRNA network with the dysregulated genes by bioinformatics methods. The TCGA and GSE4290 dataset were used to confirm the expression and prognostic value of candidate mRNAs.

Results: In total, 3413 differentially expressed lncRNAs and mRNAs, 305 differentially expressed miRNAs were indentified in GBM samples. Then a ceRNA network containing 3 lncRNAs, 5 miRNAs, and 60 mRNAs was constructed. The overall survival analysis of TCGA databases indicated that two mRNAs (C1s and HSD3B7) were remarkly related with the prognosis of GBM.

Conclusion: The ceRNA network may increase our understanding to the pathogenesis of GBM. In general, the candidate mRNAs from the ceRNA network can be predicted as new therapeutic targets and prognostic biomarkers for GBM.
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http://dx.doi.org/10.1186/s12935-020-01488-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429694PMC
August 2020

Femtosecond Laser Induced Phase Transformation of TiO with Exposed Reactive Facets for Improved Photoelectrochemistry Performance.

ACS Appl Mater Interfaces 2020 Sep 1;12(37):41250-41258. Epub 2020 Sep 1.

Laser Micro/Nano Fabrication Laboratory, School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

Titanium dioxide (TiO) is one of the most promising candidates for photoelectrochemistry applications. For a high photoelectrochemistry performance, the control of crystal structure and crystal facet is essential. The phase transformation of TiO is conventionally achieved by thermal annealing. Here, we report an approach for selective phase transformation of TiO containing exposed reactive facets with improved photoelectrochemistry performance. After femtosecond laser processing, TiO nanotubes with exposed reactive anatase {010} facets are prepared, and they have a maximum photocurrent density more than 5 times that of pure anatase. Additionally, this strategy can induce phase transformation in a selective area, which shows the advantages of patterning processing. Our method constructs a promising strategy for preparing functional nanomaterials with high performances and functionality.
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http://dx.doi.org/10.1021/acsami.0c10026DOI Listing
September 2020

Exosomes derived from TSG-6 modified mesenchymal stromal cells attenuate scar formation during wound healing.

Biochimie 2020 Oct 12;177:40-49. Epub 2020 Aug 12.

Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.

Mesenchymal stromal cell (MSC)-derived exosome therapy has emerged as an effective therapy strategy for the pathological scar formation. However, the underlying mechanisms have not been completely understood. In the current study, we investigate the therapeutic effect of TSG-6 modified MSC-derived exosomes on a mouse full-thickness wound model and provide evidence of a possible mechanism for MSC-derived exosomes to prevent from scar formation. Overexpression and knockdown of TSG-6 were conducted by lentivirus infection into hBMSCs. Exosomes were isolated from cell culture and identified by transmission electron microscopy and Western blot. C57BL/6J mice were performed of full-thickness skin wounds and treated with exosomal suspension or TSG-6-neutralizing antibody. H&E staining was subjected to observe the pathological changes of scar tissues. Immunohistochemistry, ELISA, real time-PCR and Western blot were applied to detect the expressions of relevant molecules. The results showed that subcutaneous injection of TSG-6 overexpressed MSC-derived exosomes effectively ameliorated scar pathological injury, decreased inflammatory molecular secretion and attenuated collagen deposition in a mouse skin wound model. Reversely, knockdown of TSG-6 abrogated the therapeutic effect of MSC-derived exosomes on scarring. Moreover, TSG-6-neutralizing antibody counteracted the effect of TSG-6 overexpressed MSC-derived exosomes in preventing scar formation. In conclusion, we demonstrated that exosomes derived from TSG-6 modified MSCs suppressed scar formation via reducing inflammation and inhibiting collagen deposition.
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http://dx.doi.org/10.1016/j.biochi.2020.08.003DOI Listing
October 2020