Publications by authors named "Pei Wang"

1,454 Publications

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Machine learning based personalized promotion strategy of piglets weaned per sow per year in large-scale pig farms.

Porcine Health Manag 2022 Aug 10;8(1):37. Epub 2022 Aug 10.

Key Laboratory of Applied Technology On Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology and College of Veterinary Medicine of Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an District, Hangzhou, 311300, Zhejiang, People's Republic of China.

Background: The purpose of this study was to analyze the relationship between different productive factors and piglets weaned per sow per year (PSY) in 291 large-scale pig farms and analyze the impact of the changes in different factors on PSY. We chose nine different algorithm models based on machine learning to calculate the influence of each variable on every farm according to its current situation, leading to personalize the improvement of the impact in the specific circumstances of each farm, proposing a production guidance plan of PSY improvement for every farm. According to the comparison of mean absolute error (MAE), 95% confidence interval (CI) and R, the optimal solution was conducted to calculate the influence of 17 production factors of each pig farm on PSY improvement, finding out the bottleneck corresponding to each pig farm. The level of PSY was further analyzed when the bottleneck factor of each pig farm changed by 0.5 standard deviation (SD).

Results: 17 production factors were non-linearly related to PSY. The top five production factors with the highest correlation with PSY were the number of weaned piglets per litter (WPL) (0.6694), mating rate within 7 days after weaning (MR7DW) (0.6606), number of piglets born alive per litter (PBAL) (0.6517), the total number of piglets per litter (TPL) (0.5706) and non-productive days (NPD) (- 0.5308). Among nine algorithm models, the gradient boosting regressor model had the highest R, smallest MAE and 95% CI, applied for personalized analysis. When one of 17 production factors of 291 large-scale pig farms changed by 0.5 SD, 101 pig farms (34.7%) can increase 1.41 PSY (compared to its original value) on average by adding the production days, and 60 pig farms (20.6%) can increase 1.14 PSY on average by improving WPL, 45 pig farms (15.5%) can increase 1.63 PSY by lifting MR7DW.

Conclusions: The main productive factors related to PSY included WPL, MR7DW, PBAL, TPL and NPD. The gradient boosting regressor model was the optimal method to individually analyze productive factors that are non-linearly related to PSY.
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http://dx.doi.org/10.1186/s40813-022-00280-zDOI Listing
August 2022

DAGBagM: learning directed acyclic graphs of mixed variables with an application to identify protein biomarkers for treatment response in ovarian cancer.

BMC Bioinformatics 2022 Aug 5;23(1):321. Epub 2022 Aug 5.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Background: Applying directed acyclic graph (DAG) models to proteogenomic data has been shown effective for detecting causal biomarkers of complex diseases. However, there remain unsolved challenges in DAG learning to jointly model binary clinical outcome variables and continuous biomarker measurements.

Results: In this paper, we propose a new tool, DAGBagM, to learn DAGs with both continuous and binary nodes. By using appropriate models, DAGBagM allows for either continuous or binary nodes to be parent or child nodes. It employs a bootstrap aggregating strategy to reduce false positives in edge inference. At the same time, the aggregation procedure provides a flexible framework to robustly incorporate prior information on edges.

Conclusions: Through extensive simulation experiments, we demonstrate that DAGBagM has superior performance compared to alternative strategies for modeling mixed types of nodes. In addition, DAGBagM is computationally more efficient than two competing methods. When applying DAGBagM to proteogenomic datasets from ovarian cancer studies, we identify potential protein biomarkers for platinum refractory/resistant response in ovarian cancer. DAGBagM is made available as a github repository at https://github.com/jie108/dagbagM .
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http://dx.doi.org/10.1186/s12859-022-04864-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354326PMC
August 2022

Exerkine fibronectin type-III domain-containing protein 5/irisin-enriched extracellular vesicles delay vascular ageing by increasing SIRT6 stability.

Eur Heart J 2022 Aug 4. Epub 2022 Aug 4.

Department of Pharmacology, College of Pharmacy, Second Military Medical University/Naval Medical University, Shanghai, China.

Aims: Exercise confers protection against cardiovascular ageing, but the mechanisms remain largely unknown. This study sought to investigate the role of fibronectin type-III domain-containing protein 5 (FNDC5)/irisin, an exercise-associated hormone, in vascular ageing. Moreover, the existence of FNDC5/irisin in circulating extracellular vesicles (EVs) and their biological functions was explored.

Methods And Results: FNDC5/irisin was reduced in natural ageing, senescence, and angiotensin II (Ang II)-treated conditions. The deletion of FNDC5 shortened lifespan in mice. Additionally, FNDC5 deficiency aggravated vascular stiffness, senescence, oxidative stress, inflammation, and endothelial dysfunction in 24-month-old naturally aged and Ang II-treated mice. Conversely, treatment of recombinant irisin alleviated Ang II-induced vascular stiffness and senescence in mice and vascular smooth muscle cells. FNDC5 was triggered by exercise, while FNDC5 knockout abrogated exercise-induced protection against Ang II-induced vascular stiffness and senescence. Intriguingly, FNDC5 was detected in human and mouse blood-derived EVs, and exercise-induced FNDC5/irisin-enriched EVs showed potent anti-stiffness and anti-senescence effects in vivo and in vitro. Adeno-associated virus-mediated rescue of FNDC5 specifically in muscle but not liver in FNDC5 knockout mice, promoted the release of FNDC5/irisin-enriched EVs into circulation in response to exercise, which ameliorated vascular stiffness, senescence, and inflammation. Mechanistically, irisin activated DnaJb3/Hsp40 chaperone system to stabilize SIRT6 protein in an Hsp70-dependent manner. Finally, plasma irisin concentrations were positively associated with exercise time but negatively associated with arterial stiffness in a proof-of-concept human study.

Conclusion: FNDC5/irisin-enriched EVs contribute to exercise-induced protection against vascular ageing. These findings indicate that the exerkine FNDC5/irisin may be a potential target for ageing-related vascular comorbidities.
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http://dx.doi.org/10.1093/eurheartj/ehac431DOI Listing
August 2022

In Situ Engineering of the Cu/Cu Interface to Boost C Selectivity in CO Electroreduction.

ACS Appl Mater Interfaces 2022 Aug 4. Epub 2022 Aug 4.

School of Environment and Energy, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Atmospheric Environment and Pollution Control, South China University of Technology, Guangzhou 510006, China.

The Cu/Cu interface in the Cu-based electrocatalyst is essential to promote the electrochemical reduction of carbon dioxide (ERCO) to produce multi-carbon hydrocarbons and alcohols with high selectivity. However, due to the high activity of the Cu/Cu interface, it is easy to be oxidized in the air. How to control and prepare a Cu-based electrocatalyst with an abundant and stable Cu/Cu interface in situ is a huge challenge. Here, combined with density functional theory (DFT) calculations and experimental studies, we found that the trace halide ions adsorbed on CuO can slow the reduction kinetics of Cu → Cu, which allowed us to in-situ well control the synthesis of the CuO-derived electrocatalyst with rich Cu/Cu interfaces. Our Cu catalyst with a rich Cu/Cu interface exhibits excellent ERCO performance. Under the operation potential of -0.98 V versus RHE, the Faraday efficiency of CH and C products are 55.8 and 75.7%, respectively, which is about 16% higher than that of CuO-derived electrocatalysts that do not use halide ions. The high comes from the improvement of the coupling efficiency of reaction intermediates such as CO-CO, which is proved by DFT calculations, and the suppression of hydrogen evolution reaction. Therefore, we provide an in-situ engineering strategy, which is simple and effective for the design and preparation of high-performance ERCO catalysts.
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http://dx.doi.org/10.1021/acsami.2c05992DOI Listing
August 2022

Population pharmacokinetics and clinical outcomes of polymyxin B in paediatric patients with multidrug-resistant Gram-negative bacterial infections.

J Antimicrob Chemother 2022 Aug 4. Epub 2022 Aug 4.

Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Current polymyxin B dosing in children relies on scant data.

Objectives: To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages.

Methods: A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33-2.53 mg/kg/day), and the median age was 12.5 (range 3.2-17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed.

Results: PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50-100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5-3.0 mg/kg/day had a probability of target attainments over 90% when MICs were <0.5 mg/L.

Conclusions: Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are <0.5 mg/L.
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http://dx.doi.org/10.1093/jac/dkac265DOI Listing
August 2022

Seawater intrusion induced cadmium activation via altering its distribution and transformation in paddy soil.

Chemosphere 2022 Jul 30;307(Pt 2):135805. Epub 2022 Jul 30.

National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou, 510650, PR China.

Seawater intrusion can cause environmental risks to paddy soils around estuaries, but the impacts on the availability of heavy metals are still unclear. River water and sea water were collected along the river of an estuary. A stirred-flow experiment was conducted to examine the Cd desorption behavior in Cd-contaminated paddy soil. While the pH increased with increasing salinity levels, more Cd was released with increasing salinity, suggesting that Cd competition by cations and complexation by anions, but not pH, dominated the release of Cd from soils. Moreover, paddy soil was incubated at different salinities under alternating redox conditions. The availability of Cd, as indicated by the diffusive gradients in thin film (DGT), became relatively high with increasing salinity levels during the initial anaerobic and later aerobic stages. The available Cd fractions substantially decreased under anaerobic condition, and then rapidly increased under aerobic condition. When oxygen was introduced into the system, Cd associated with organic matter and Fe-Mn oxides were released, and oxidative dissolution of Cd sulfides was observed, especially in the high salinity treatment. Seawater intrusion affects biogeochemical cycles and can promote rapid export of NH, Fe, and SO in paddy soils, especially in soils with high salinity. Our findings demonstrated that the high salinity content in paddy soil significantly enhanced the availability of Cd, especially during the drainage stage.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135805DOI Listing
July 2022

Persistent hiccup as one of the initial symptoms of leucine-rich glioma-inactivated-1 encephalitis: a case report.

BMC Neurol 2022 Jul 27;22(1):281. Epub 2022 Jul 27.

Department of Neurology, Baoding No.1 Central Hospital, 320 Northern Great Wall Street, Hebei Province, 071000, Baoding, China.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, an autoimmune disorder, is characterized by faciobrachial dystonic seizures, epilepsy, memory deficits and altered mental status while hiccup is not commonly found in patients.

Case Presentation: A 62-year-old male was presented with slurred speech, abnormal gait, faciobrachial dystonic seizures and impaired cognition. Besides, the hiccup was one of the initial symptoms. His brain magnetic resonance images (MRI) revealed multiple lesions with left caudate nucleus, putamen, insula and left hippocampus involvement. Because a diagnosis of antibody-related limbic encephalitis was suspected, studies including an autoimmune profile were done by cell-based assays. After anti-LGI1 antibodies were detected in both cerebrospinal fluid and serology, pulse methylprednisolone and intravenous immunoglobulin were started and hence hiccups disappeared along with other symptoms.

Conclusions: Clinicians should be aware that persistent hiccups might be one of the initial manifestations of LGI1 subtype of voltage-gated potassium channel complex antibody associated autoimmune encephalitis.
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http://dx.doi.org/10.1186/s12883-022-02797-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327253PMC
July 2022

Molecular Characterization of spp. in Pigs with Diarrhea in Southern China.

Animals (Basel) 2022 Jul 9;12(14). Epub 2022 Jul 9.

College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China.

spp. is a common zoonotic intestinal protozoan that can parasitize most vertebrates, including humans and pigs, causing severe intestinal diseases and posing a serious threat to public health. However, the available data on spp. infection in pigs are relatively limited in China. To characterize the infection of spp. within pigs in southern China, 1254 fecal samples of diarrheic pigs were collected from 37 intensive pig farms in Hunan, Jiangxi and Fujian provinces and the infection of spp. was investigated based on the small subunit rRNA (SSU rRNA) gene. The overall infection rate of spp. was 58.4% (732/1254), including 38.4% (118/307) in suckling piglets, 51.2% (153/299) in weaned piglets, 57.9% (55/95) in fattening pigs and 73.4% (406/553) in sows, respectively. Moreover, age and the sampling cities in Jiangxi and Fujian provinces were found to be the key factors influencing the infection of spp. ( < 0.05). Two subtypes (ST1 and ST3) with a zoonotic potential of and were detected in all age groups of pigs and all sampling areas, with the predominant species and predominant subtype being (91.3%, 668/732) and ST1 (573/668), respectively, and ST1 + ST3 (78.6%, 239/304) being the most frequently detected form of mixed infection. Severe spp. infection and zoonotic subtypes were found in this study, exposing a large public health problem in the study area, and strategies need to be implemented to eliminate the risk in the future.
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http://dx.doi.org/10.3390/ani12141764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311668PMC
July 2022

Effects of different potassium-lowering regimens on acute hyperkalemia in hemodialysis patients: a real-world, retrospective study.

J Transl Med 2022 07 25;20(1):333. Epub 2022 Jul 25.

Blood Purification Center, Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, 450052, Henan, China.

Background: Hyperkalemia is a common and potentially life-threatening electrolyte disorder in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the efficacy and safety of potassium-lowering regimens during treatment of acute hyperkalemia in MHD patients.

Methods: This retrospective real-world study (RWS) was conducted among 139 MHD patients. They were given different potassium-lowering regimens, viz. the insulin and glucose (IG) intravenous administration group (IG, 46 patients), the sodium polystyrene sulfonate group (SPS, 33 patients), the sodium zirconium cyclosilicate group (SZC, 38 patients), the IG + SZC group (22 patients). The primary efficacy end point was the rate of serum potassium decline at 2 h. The rates of adverse events were also compared.

Results: At 2 h, the mean ± SE change of serum potassium level was - 0.71 ± 0.32 mmol per liter (mmol/L) in IG group, - 0.43 ± 0.38 mmol/L in SPS group, - 0.64 ± 0.36 mmol/L in SZC group, - 1.43 ± 0.38 mmol/L in IG + SZC group (P < 0.01). The serum potassium level in IG + SZC group decreased more than that in the other three groups (P < 0.01), while the serum potassium level in SPS group decreased less than that in the other three groups (P < 0.05). There was no significant difference on the decrease of the serum potassium level between IG group and the SZC group (P = 0.374). The IG group and the IG + SZC group had higher rates of symptomatic hypoglycemia. The SPS group had significant decreases of serum calcium and serum magnesium after treatment.

Conclusions: Among MHD patients with acute hyperkalemia, SZC had similar potassium-lowering efficacy with IG intravenous administration at 2 h and superior on convenience and side-effects.
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http://dx.doi.org/10.1186/s12967-022-03530-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310460PMC
July 2022

Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects.

Front Nutr 2022 5;9:919484. Epub 2022 Jul 5.

Hubei Key Laboratory of Food Nutrition and Safety, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Epidemiologic studies on cruciferous vegetable (CV) intake and cardiovascular disease (CVD) were inconclusive.

Objective: To investigate the associations of urinary thiocyanate, a biomarker of CV intake, with CVD and all-cause mortality among non-smoking adults.

Methods: This prospective cohort study comprised 10,489 non-smoking adults (weighted mean age, 46.8 years; 43.4% male) from the National Health and Nutrition Examination Survey 2001-2014. Non-smokers were defined as subjects with serum cotinine < 3 ng/mL. Urinary thiocyanate was measured with ion chromatography tandem mass spectrometry at baseline, and CVD and all-cause mortality were identified through linkage to National Death Index until December 31, 2015. Cox proportional hazards model was applied to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD and all-cause mortality.

Results: A total of 800 deaths, of which 136 died of CVD, were ascertained within a median 7.8 years of follow-up. Urinary thiocyanate was positively correlated with total CV intake among non-smoking adults ( = 0.088, < 0.001). Comparing extreme quartiles, the multivariate-adjusted HRs for CVD and all-cause mortality were 0.50 (95% CI: 0.29-0.85) and 0.75 (95% CI: 0.60-0.92), respectively. Each 1 μg/g creatinine increment of log-transformed urinary thiocyanate was associated with a 25% (HR: 0.75; 95% CI: 0.62-0.91) reduced CVD mortality risk and 12% (HR: 0.88; 95% CI: 0.81-0.96) reduced all-cause mortality risk. The documented inverse associations persisted in sensitivity analyses.

Conclusion: Increased levels of urinary thiocyanate, a candidate biomarker of CV intake, were associated with low risks of CVD and total mortality among non-smoking adults. This prospective biomarker-based study provided further evidence to support the cardiovascular benefits of CVs.
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http://dx.doi.org/10.3389/fnut.2022.919484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294399PMC
July 2022

Associations between antenatal maternal asthma status and placental DNA methylation.

Placenta 2022 Aug 3;126:184-195. Epub 2022 Jul 3.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Introduction: Maternal asthma in pregnancy is associated with adverse perinatal and child health outcomes; however, mechanisms are poorly understood.

Methods: The PRogramming of Intergenerational Stress Mechanisms (PRISM) prospective pregnancy cohort characterized asthma history during pregnancy via questionnaires and quantified placental DNAm using the Illumina Infinium HumanMethylation450 BeadChip. We performed epigenome-wide association analyses (n = 223) to estimate associations between maternal active or inactive asthma, as compared to never asthma, and placental differentially methylated positions (DMPs) and differentially variable positions (DVPs). Models adjusted for maternal pre-pregnancy body mass index, smoking status, parity, age and education level and child sex. P-values were FDR-adjusted.

Results: One hundred and fifty-nine (71.3%) pregnant women reported no history of asthma (never asthma), 15 (6.7%) reported inactive, and 49 (22%) reported active antenatal asthma. Women predominantly self-identified as Black/Hispanic Black [88 (39.5%)] and Hispanic/non-Black [42 (18.8%)]. We identified 10 probes at FDR<0.05 and 4 probes at FDR<0.10 characterized by higher variability in maternal active asthma compared to never asthma mapping to GPX3, LHPP, PECAM1, ATAD3C, and ARHGEF4 and 2 probes characterized by lower variation mapping to CHMP4A and C5orf24. Amongst women with inactive asthma, we identified 52 probes, 41 at FDR<0.05 and an additional 11 at FDR <0.10, with higher variability compared to never asthma; BMP4, LHPP, PHYHIPL, and ZSCAN23 were associated with multiple DVPs. No associations were observed with DMPs.

Discussion: We observed alterations in placental DNAm in women with antenatal asthma, as compared to women without a history of asthma. Further research is needed to understand the impact on fetal development.
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http://dx.doi.org/10.1016/j.placenta.2022.06.008DOI Listing
August 2022

Transanal full-thickness pull-through approach in the treatment of anastomotic leakage after operation for Hirschsprung disease.

Pediatr Surg Int 2022 Sep 19;38(9):1263-1271. Epub 2022 Jul 19.

Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.

Background: Anastomotic leakage (AL) is one of the most perplexing complications that can occur following a radical operation to treat Hirschsprung disease (HSCR). The purpose of this study was to document our experience with anastomotic leakage following radical HSCR surgery to enhance therapeutic effect and prognosis.

Methods: Between January 2007 and April 2021, a retrospective study was conducted on 12 children who developed anastomotic leakage following radical surgery for HSCR. Medical records were analyzed to determine the clinical manifestations, primary surgical procedures, evaluation methods, surgical plans, and outcomes of the patients. To assess postoperative bowel function, the Rintala score was used.

Results: The Soave procedure was used as the primary surgical method in seven cases (58.3%), the Swenson procedure was used in four cases (33.3%), and the Rehbein procedure was used in one case (8.3%). Enterostomy (10, 83.3%) and conservative treatment (2, 16.7%) were performed when anastomotic leakage was diagnosed. Two patients who directly closed stoma without redoing pull-through both accepted enterostomy within 48 h. One female with anastomotic fistula who was closed leakage or fistula in situ had to endure lifelong stoma. Other patients who underwent redo pull-through procedures had normal bowel function. Seven patients underwent a redo pull-through procedure. Three of them preferred the transanal full-thickness pull-through (FTPT) approach, while four preferred the Soave technique. Three children had mild postoperative soiling, which improved with conservative treatment. Bowel function score was 17.5 ± 1.1.

Conclusion: Enterostomy should be performed immediately if anastomotic leakage occurs. After leakage, it is necessary to redo the pull-through procedure in an anastomotic fistula or anastomotic stricture. Transanal FTPT reconstruction is an effective method for repairing anastomoses and leakage.
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http://dx.doi.org/10.1007/s00383-022-05164-5DOI Listing
September 2022

Three unusual hybrid sorbicillinoids with anti-inflammatory activities from the deep-sea derived fungus Penicillium sp. SCSIO06868.

Phytochemistry 2022 Jul 10;202:113311. Epub 2022 Jul 10.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China. Electronic address:

Under the guidance of MS/MS based molecular networking, bisorbicillchaetones A-C, three undescribed hybrid sorbicillinoids, were isolated from cultures of the deep-sea derived fungus Penicillium sp. SCSIO06868. The planar structures and absolute configurations of these compounds were determined by extensive spectroscopic analyses. Bisorbicillchaetones are the first examples of hybrid sorbicillinoids containing a coniochaetone unit. Bisorbicillchaetones A and B exhibited moderate inhibitory effect on NO production in LPS activated RAW264.7 cells with the IC values of 80.3 ± 3.6 μM and 38.4 ± 3.3 μM, respectively, without cytotoxicity observed.
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http://dx.doi.org/10.1016/j.phytochem.2022.113311DOI Listing
July 2022

A DNA-Cu nanocluster and exonuclease I integrated label-free reporting system for CRISPR/Cas12a-based SARS-CoV-2 detection with minimized background signals.

J Mater Chem B 2022 Jul 13. Epub 2022 Jul 13.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.

CRISPR-driven biosensing is developing rapidly, but current studies mostly adopt dye-labeled ssDNA as the signal reporter, which is costly and unstable. Herein, we developed a label-free and low-background reporter for CRISPR/Cas12a signaling by integrating DNA-templated copper nanoclusters (DNA-CuNCs) and exonuclease I (EXO I). The template of the DNA-CuNCs was rationally designed as a ds-/ss-DNA hybrid, ensuring that after a quick and nonpersistent cut of Cas12a, a majority of the template can be digested by EXO I. Based on this novel reporter, a biosensor termed CRISPR-CNS (cost-effective, nimble, and sensitive copper nanocluster sensor integrating CRISPR) was developed. Due to the high signal-to-background ratio of our proposed reporter, CRISPR-CNS shows excellent performances for nucleic acid detection, yielding a detection limit of 20 copies for SARS-CoV-2 RNA. Considering its facile synthesis, robust fluorescence, effective cost, and good sensitivity, this combination shall serve as a highly potential output for CRISPR-based point-of-care testing.
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http://dx.doi.org/10.1039/d2tb00857bDOI Listing
July 2022

Visible-Light-Driven Photocatalytic Cellulose-to-H2 Conversion by MoS2/ZnIn2S4 Photocatalyst with the Assistance of Cellulase.

Chemphyschem 2022 Jul 11. Epub 2022 Jul 11.

Hangzhou Dianzi University, College of Materials and Environmental Engineering, Baiyang Street 3118, Hangzhou, Zhejiang, P.R.China, 310018, Hangzhou, CHINA.

Visible-light-driven photocatalytic cellulose-to-H 2 conversion system was successfully constructed by using MoS 2 /ZnIn 2 S 4 as the photocatalyst and cellulase as the enzyme catalyst. In this smartly-designed system, the cellulose was firstly converted to glucose by the action of cellulase, and the generated glucose acted as an efficient holes trapper and electron donor which was further converted into H 2 through photocatalytic reaction over MoS 2 /ZnIn 2 S 4 photocatalyst under visible light irradiation. The optimum H 2 generation rate achieves 12.2 μmol·h -1 ·g -1 with respect to photocatalyst under visible light irradiation (λ>420 nm) in photocatalytic system in the presence of 100 mg 3% MoS 2 /ZnIn 2 S 4 , 100 mg cellulase and 2 g poplar wood chip. These results open up a new possibility for the development of efficient visible-light-responding photocatalytic cellulose -to-H 2 conversion system that combine photocatalysis and enzyme technology.
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http://dx.doi.org/10.1002/cphc.202200319DOI Listing
July 2022

Predictive Value of Geriatric Nutritional Risk Index in Patients With Lower Extremity Peripheral Artery Disease: A Meta-Analysis.

Front Nutr 2022 22;9:903293. Epub 2022 Jun 22.

Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.

Background: Conflicting results have been reported on the value of the Geriatric Nutritional Risk Index (GNRI) in predicting adverse outcomes in patients with peripheral artery disease (PAD). The objective of this meta-analysis was to evaluate the association of GNRI with adverse outcomes in patients with lower extremity PAD.

Methods: Relevant studies were comprehensively searched in PubMed and Embase databases until December 31, 2021. Eligible studies should evaluate the value of GNRI in predicting major adverse cardiovascular and leg events (MACLEs), all-cause mortality, and amputation in patients with lower extremity PAD.

Results: Eight studies reporting on 9 articles involving 5,541 patients were included. A fixed-effect model meta-analysis showed that patients with PAD with low GNRI had an increased risk of MACLEs [adjusted risk ratio (RR) 2.26; 95% confidence interval (CI) 1.54-3.31] and all-cause mortality (RR 2.38; 95% CI 1.71-3.31) compared with those with high GNRI. When analysis of GNRI is by continuous data, 10 units of GNRI decrease was associated with 36% and 44% higher risk of MACLEs and all-cause mortality, respectively. However, per 10 units GNRI score decrease was not significantly associated with a higher risk of amputation ( = 0.051).

Conclusion: Low GNRI may be an independent predictor of adverse outcomes in patients with lower extremity PAD. Routine screening of nutritional status using the GNRI may provide important prognostic information in patients with PAD.
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http://dx.doi.org/10.3389/fnut.2022.903293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257164PMC
June 2022

Incidence and risk factors of left ventricular thrombus in acute ST-segment elevation myocardial infraction treated by primary percutaneous coronary intervention: a meta-analysis.

Med Princ Pract 2022 Jul 7. Epub 2022 Jul 7.

Objective: Left ventricular thrombosis (LVT) is a common complication of acute ST-segment elevation myocardial infarction (STEMI). This study attempted to synthesize the available evidence to understand the incidence and risk factors of LVT in acute STEMI patients undergoing primary percutaneous coronary intervention (PCI).

Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for studies published from January 2001 to January 2022. The random-effects and fixed-effects model meta-analysis estimated pooled incidence, mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). Review Manager 5.4 software was used for meta-analysis performance.

Results: The results of meta- analysis showed that the incidence of LVT in acute STEMI treated by primary PCI was 4% [95% CI (0.03, 0.05)], and the overall pooled incidence in patients with anterior STEMI was 10.0% [95% CI (0.07, 0.12)]. Anterior STEMI [OR =11.93, 95%CI (6.25,22.78), p =0.0003.], left anterior descending-related infarct [OR =6.85, 95%CI (3.70,12.66), p< 0.00001.], left ventricular wall motion abnormalities [OR =7.53, 95%CI (3.18,17.82), p< 0.00001.], and lower post-PCI LVEF [MD = 13.78, 95%CI (12.15, 15.41), p< 0.00001.] were risk factors for post-PCI LVT.

Conclusion: The incidence of LVT after acute STEMI in the PCI era remains high. This study provides a preliminary overview of STEMI patients at risk for post-PCI LVT and will help the design of prospective randomized controlled trials(RCTs) for the management and prevention of LVT.
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http://dx.doi.org/10.1159/000525943DOI Listing
July 2022

Evaluation on Effect of Acupoint Application to Treat Idiopathic Edema of Perimenopausal Women Using the Segmentation Dictionary Learning Algorithm.

Comput Intell Neurosci 2022 27;2022:2196782. Epub 2022 Jun 27.

Centre of Traditional Chinese Medical Science, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing 101149, China.

This study aimed to explore the effect of ultrasound imaging in the diagnosis and evaluation of acupoint application in the treatment of idiopathic edema. In this study, an ultrasound imaging diagnosis based on the segmentation dictionary learning (S-DL) algorithm was proposed. In addition, the autoencoding algorithm (ASE) was compared with the traditional dictionary learning (DL) algorithm. The treatment effect, associated quantitative integral, and quality of life score of patients in two groups were compared. The results showed that the peak signal-to-noise ratio (PSNR), root mean square error (RMSE), and structural similarity (SSIM) of the S-DL algorithm were 32.45 dB, 0.654, and 0.0012, respectively, which were quite different compared to the ASE and DL algorithms, showing statistical significance ( < 0.05). As the noise level increased, the image reconstruction quality gradually decreased, but the S-DL algorithm obtained better image quality than the DL and ASE algorithms, and the difference was statistically great ( < 0.05). There was no significant difference in the average age and average course of the disease between the experimental group and the control group ( > 0.05). The overall treatment effect of patients in the experimental group was 96.77%, while that in the control group was 45.16%, and the difference between the two was statistically significant ( < 0.05). After treatment, the semiquantitative scores of fatigue, dizziness, palpitation, frequent urination, urgent urination, and dyspepsia of the experimental group were 1.18, 0.39, 0.72, 1.21, and 0.87, respectively, which were much lower than those of the control group statistically ( < 0.05). The score of quality of life of the experimental group of patients after treatment was 91.27 points, and that of the control group was 82.35 points, showing statistically great difference ( < 0.05). It showed that the algorithm performance of S-DL was relatively good, and the acupoint application therapy was better than traditional western medicine in the treatment of idiopathic edema, which reduces the discomfort of patients to a certain extent and improves the quality of life of patients.
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http://dx.doi.org/10.1155/2022/2196782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252663PMC
July 2022

Construction of a Six-Gene Prognostic Risk Model Related to Hypoxia and Angiogenesis for Cervical Cancer.

Front Genet 2022 13;13:923263. Epub 2022 Jun 13.

TCM Gynecology Department, Foshan Fosun Chancheng Hospital, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, China.

The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model. Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves. Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes ( and ). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, < 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores. We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.
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http://dx.doi.org/10.3389/fgene.2022.923263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234147PMC
June 2022

Internal Standard Triggered-Parallel Reaction Monitoring Mass Spectrometry Enables Multiplexed Quantification of Candidate Biomarkers in Plasma.

Anal Chem 2022 07 29;94(27):9540-9547. Epub 2022 Jun 29.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States.

Despite advances in proteomic technologies, clinical translation of plasma biomarkers remains low, partly due to a major bottleneck between the discovery of candidate biomarkers and costly clinical validation studies. Due to a dearth of multiplexable assays, generally only a few candidate biomarkers are tested, and the validation success rate is accordingly low. Previously, mass spectrometry-based approaches have been used to fill this gap but feature poor quantitative performance and were generally limited to hundreds of proteins. Here, we demonstrate the capability of an internal standard triggered-parallel reaction monitoring (IS-PRM) assay to greatly expand the numbers of candidates that can be tested with improved quantitative performance. The assay couples immunodepletion and fractionation with IS-PRM and was developed and implemented in human plasma to quantify 5176 peptides representing 1314 breast cancer biomarker candidates. Characterization of the IS-PRM assay demonstrated the precision (median % CV of 7.7%), linearity (median > 0.999 over 4 orders of magnitude), and sensitivity (median LLOQ < 1 fmol, approximately) to enable rank-ordering of candidate biomarkers for validation studies. Using three plasma pools from breast cancer patients and three control pools, 893 proteins were quantified, of which 162 candidate biomarkers were verified in at least one of the cancer pools and 22 were verified in all three cancer pools. The assay greatly expands capabilities for quantification of large numbers of proteins and is well suited for prioritization of viable candidate biomarkers.
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http://dx.doi.org/10.1021/acs.analchem.1c04382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280723PMC
July 2022

Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation.

J Med Chem 2022 07 28;65(13):8798-8827. Epub 2022 Jun 28.

School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

Proteolysis-targeting chimeras (PROTACs) is a fast-growing technology providing many strengths over inhibition of protein activity directly and is attracting increasing interest in new drug discovery and development. However, efficiently identifying potent and drug-like degraders is still challenging in the development of PROTACs. Complementary to traditional PROTACs, several emerging types of PROTACs, such as homobivalent PROTACs based on two E3 ligases (e.g., CRBN, VHL, MDM2, TRIM24), chemical- or biological-based trivalent/multitargeted PROTACs, and covalent PROTACs, are rising for targeted protein degradation. These new types of PROTACs have several advantages over the traditional PROTACs including high selectivity, low toxicity, better therapeutic effects, and so on. In this perspective, we will summarize the latest development of representative PROTACs focusing on research mainly in past 10 years and discuss their advantages and disadvantages. Moreover, the outlook and perspectives on the associated challenges and future directions will be provided.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00728DOI Listing
July 2022

Receptor-like kinase HAESA-like 1 positively regulates seed longevity in Arabidopsis.

Planta 2022 Jun 28;256(2):21. Epub 2022 Jun 28.

College of Life Sciences, Nankai University, Tianjin, 300071, China.

Main Conclusion: Based on the phenotypic, physiological and transcriptomic analysis, receptor-like kinase HAESA-like 1 was demonstrated to positively affect seed longevity in Arabidopsis. Seed longevity is very important for both genetic resource conservation and crop production. Receptor-like kinases (RLKs) are widely involved in plant growth, development and stress responses. However, the role of most RLKs, especially in seed longevity, is largely unknown. In this study, we report that Arabidopsis HAESA-like 1 (AtHSL1) positively regulated seed longevity. Disruption of HSL1 significantly decreased the germination rate to 50% at 7 days after cold stratification (DAC), compared with that of the wild type (93.5% at 7 DAC), after accelerated aging treatment. Expression of the HSL1 gene in hsl1 basically restored the defective phenotype (86.3%), while HSL1-overexpressing lines (98.3%) displayed slower accelerated aging than WT (93.5%). GUS staining revealed HSL1 was highly expressed universally, especially in young seedlings, mature seeds and embryos of imbibed seeds, and its expression could be induced by accelerated aging. No difference in the dyeing color and area of mucilage were identified between WT and hsl1. The soluble pectin content also was not different, while the adherent pectin content was significantly increased in hsl1. Global transcriptomics revealed that disruption of HSL1 mainly downregulated genes involved in trehalose synthesis, nucleotide sugar metabolism and protection and repair mechanisms. Therefore, an increase in adherent pectin content and downregulation of genes involved in trehalose synthesis may be the main reasons for decreasing seed longevity owing to disruption of HSL1 in Arabidopsis. Our work provides valuable information for understanding the function and mechanism of a receptor-like kinase, AtHSL1, in seed longevity.
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http://dx.doi.org/10.1007/s00425-022-03942-yDOI Listing
June 2022

Immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults.

Immun Inflamm Dis 2022 07;10(7):e670

Department of Laboratory Medicine and Blood Transfusion, The First People's Hospital of Jingmen, Hubei, China.

Background: Asymptomatic infections may play an important role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Delta variant transmissions. However, the immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults remain to be defined.

Methods: A retrospective study involving 36 vaccinated adults infected with the SARS-CoV-2 Delta variant was performed. Their demographic and laboratory data were collected and analyzed in The First People's Hospital of Jingmen from August 4 to 20, 2021.

Results: Of the 36 adults, 6 persons had an asymptomatic infection. The severity of the SARS-CoV-2 infections was highly correlated with the doses of vaccinations (p = 0.019). The symptomatic and asymptomatic infected SARS-CoV-2 adults showed normal levels of leukocytes and lymphocytes. The C-reactive protein (CRP) and interleukin-6 (IL-6) levels were elevated in the symptomatic groups. The period between the last vaccination to the time of infection in the asymptomatic group was longer than that in the mild and moderate groups (73 vs. 61 vs. 50 days; p = 0.047). The percentage of suppressor T-cells in the asymptomatic group was the highest (32.2 ± 4.0% vs. 22.0 ± 7.2% vs. 29.3 ± 8.0%; p = 0.004). The signal-to-cutoff ratio value of total antibody against SARS-CoV-2 in the asymptomatic group was lower than that in the other two groups (383 vs. 703 vs. 1792; p < 0.001) and much lower than that in the moderate group. The multivariate ordinal logistic analysis after adjusting for gender, vaccination date, and vaccination dose indicated that CRP at Days 4-7 and 8-14, IL-6 on Days 4-7, and total antibody were risk factors for coronavirus disease 2019 severity.

Conclusions: Asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults tend to infect persons vaccinated twice. The immunophenotype profile for asymptomatic postvaccination infections is less inflammatory and accompanied by relatively lower antibody titers.
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http://dx.doi.org/10.1002/iid3.670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210569PMC
July 2022

Low positivity rates for HBeAg and HBV DNA in rheumatoid arthritis patients: a case-control study.

BMC Infect Dis 2022 Jun 24;22(1):570. Epub 2022 Jun 24.

Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta Road (w), Xi'an, 710061, Shaanxi Province, China.

Background: The rates of hepatitis B virus (HBV) infection in rheumatoid arthritis (RA) patients are controversial when considering the reported outcomes. It was speculated that HBV infection status was altered after RA, and variations inn HBV infection rates became apparent.

Methods: To compare the positive proportions of hepatitis B e antigen (HBeAg) and HBV DNA, a retrospective case-control study was performed between 27 chronic hepatitis B (CHB) patients with RA and 108 age- and gender-matched CHB patients. In addition, the positivity rates of hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) were surveyed among the 892 RA patients.

Results: Compared to CHB patients, CHB patients with RA exhibited lower rates of HBeAg positivity (11.1% vs. 35.2%, P = 0.003), HBV DNA positivity (37.0% vs. 63.9%, P = 0.007) and ALT elevation (11.1% vs. 35.2%, P = 0.024). In the 892 RA patients, the prevalence of HBsAg (3.0%) was lower than that reported in the Chinese national data (7.2%), whereas the anti-HBc positivity rate of 44.6% was higher than that of 34.1%.

Conclusion: HBV infection status was altered after suffering from RA. Compared to the matched CHB patients, low positive proportions of HBeAg and HBV DNA were observed for CHB patients with RA.
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http://dx.doi.org/10.1186/s12879-022-07536-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229421PMC
June 2022

A Glycolipid α-GalCer Derivative, 7DW8-5 as a Novel Mucosal Adjuvant for the Split Inactivated Influenza Vaccine.

Viruses 2022 05 28;14(6). Epub 2022 May 28.

Department of Biopharmacy, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, with the withdrawal of cholera toxin and Escherichia coli heat-labile endotoxin from clinical use due to side effects, there are no approved adjuvants for intranasal vaccines. Therefore, safe and effective mucosal adjuvants are urgently needed. Previously, we reported that one derivative of α-Galactosylceramide (α-GalCer), 7DW8-5, could enhance the protective efficacy of split influenza vaccine by injection administration. However, the mucosal adjuvanticity of 7DW8-5 is still unclear. In this study, we found that 7DW8-5 promotes the production of secret IgA antibodies and IgG antibodies and enhances the protective efficacy of the split influenza vaccine by intranasal administration. Furthermore, co-administration of 7DW8-5 with the split influenza vaccine significantly reduces the virus shedding in the upper and lower respiratory tract after lethal challenge. Our results demonstrate that 7DW8-5 is a novel mucosal adjuvant for the split influenza vaccine.
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http://dx.doi.org/10.3390/v14061174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230830PMC
May 2022

Nonlinear Modeling Study of Aerodynamic Characteristics of an X38-like Vehicle at Strong Viscous Interaction Regions.

Entropy (Basel) 2022 Jun 17;24(6). Epub 2022 Jun 17.

Computational Aerodynamics Institute, China Aerodynamics Research and Development Center, Mianyang 621000, China.

Strong viscous interaction and multiple flow regimes exist when vehicles fly at high altitude and high Mach number conditions. The Navier-Stokes(NS) solver is no longer applicable in the above situation. Instead, the direct simulation Monte Carlo (DSMC) method or Boltzmann model equation solvers are usually needed. However, they are computationally more expensive than the NS solver. Therefore, it is of great engineering value to establish the aerodynamic prediction model of vehicles at high altitude and high Mach number conditions. In this paper, the hypersonic aerodynamic characteristics of an X38-like vehicle in typical conditions from 70 km to 110 km are simulated using the unified gas kinetic scheme (UGKS), which is applicable for all flow regimes. The contributions of pressure and viscous stress on the force coefficients are analyzed. The viscous interaction parameters, Mach number, and angle of attack are used as independent variables, and the difference between the force coefficients calculated by UGKS and the Euler solver is used as a dependent variable to establish a nonlinear viscous interaction model between them in the range of 70-110 km. The evaluation of the model is completed using the correlation coefficient and the relative orthogonal distance. The conventional viscous interaction effect and rarefied effect are both taken into account in the model. The model can be used to quickly obtain the hypersonic aerodynamic characteristics of X38-like vehicle in a wide range, which is meaningful for engineering design.
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http://dx.doi.org/10.3390/e24060836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222802PMC
June 2022

Mechanistic and modeling insights into the immobilization of Cd and organic carbon during abiotic transformation of ferrihydrite induced by Fe(II).

J Hazard Mater 2022 08 25;436:129216. Epub 2022 May 25.

State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of the Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China.

Iron (Fe) oxides and fulvic acid (FA) are the key components affecting the fate of cadmium (Cd) in soil. The presence of FA influences Fe mineral transformation, and FA may complicate phase transformation and dynamic behavior of Cd. How varying Fe minerals and FA affect Cd immobilization during the ferrihydrite transformation induced by various Fe(II) concentrations, however, is still lack of quantitative understanding. In this study, we built a model for Cd species quantification during phase transformation based on mechanistic insights obtained from batch experiments. Spectroscopic analysis showed that Fe(II) concentrations affected secondary Fe minerals formation under the condition of co-existence of Cd and FA, and ultimately changed the distribution of Cd and FA. Microscopic analysis revealed that besides surface adsorption, part of Cd was sequestrated by magnetite, whereas FA was able to diffuse into lepidocrocite defects. The model revealed that adsorbed Cd was mainly controlled by FA and ferrihydrite, and direct complexation of Cd by FA had a strong impact on the continuous change in Cd at lower Fe(II) concentration. The results contribute to an in-depth understanding of the mobility of Cd in the environment and provide a method for quantifying the dynamic behavior of heavy metals in multi-reactant systems.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129216DOI Listing
August 2022

Tas2R activation relaxes airway smooth muscle by release of Gα targeting on AChR signaling.

Proc Natl Acad Sci U S A 2022 06 23;119(26):e2121513119. Epub 2022 Jun 23.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, 210008, China.

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor-mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gα proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gα released by Tas2R activation complexes with AChR and blocks the Gα cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gα-associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD.
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http://dx.doi.org/10.1073/pnas.2121513119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245679PMC
June 2022

Editorial: Methods for Single-Cell and Microbiome Sequencing Data.

Front Genet 2022 13;13:920191. Epub 2022 May 13.

Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States.

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http://dx.doi.org/10.3389/fgene.2022.920191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208326PMC
May 2022

A 10-Year Community-Based Study of Leucine-Rich Repeat Kinase 2 G2385R Carriers' Conversion to Parkinson's Disease.

Mov Disord 2022 Jun 22. Epub 2022 Jun 22.

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The G2385R variant of leucine-rich repeat kinase 2 (LRRK2) is mainly associated with Parkinson's disease(PD) in Asian populations.

Objective: The aim of this study was to investigate the PD conversion rate and clinical characteristics of LRRK2 G2385R nonmanifesting carriers.

Methods: All participants were from the community-based longitudinal cohort of Shanghai Ruijin Hospital. The G2385R carriers and noncarriers were screened by Sanger sequencing and received face-to-face interviews at baseline and follow-up assessments. The Kaplan-Meier method was used to compare the conversion rate of PD. Cox regression models were used to estimate the risk of G2385R variant for PD.

Results: In the combined cohort, 26 (7.9%) people developed PD in 329 carriers versus 9 (2.6%) in 345 noncarriers (P = 0.0016). Cox regression model confirmed that the G2385R variant was a strong risk factor for PD in a Chinese population older than 50 years (hazard ratio, 3.314; 95% confidence interval, 1.551-7.078; P = 0.002). No difference was found in clinical symptoms between carriers and noncarriers.

Conclusions: We confirmed an increased conversion of PD in leucine-rich repeat kinase 2 G2385R carriers during a 10-year follow-up. © 2022 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.29127DOI Listing
June 2022
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