Publications by authors named "Yajie Zhang"

325 Publications

Cryopreservation of stool samples altered the microbial viability quantitively and compositionally.

Arch Microbiol 2022 Aug 16;204(9):557. Epub 2022 Aug 16.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Stool is the most commonly used sample for gut microbiota analysis in humans and animals. Cryopreservation of stool at - 80 °C is a feasible and simple method in clinics and researches, especially in large-scale cohort studies. However, the viability of bacteria in stool after freezing has yet well-demonstrated quantitatively and compositionally. This study determined the viable microbiota of samples under cryopreservation at - 80 °C, relative to fresh samples and that stored at ambient. Stool samples were collected from three healthy adults. Propidium monoazide treatment combined with quantitative PCR and 16S rRNA gene sequencing was performed to target viable microbiota. After freezing, the number of viable bacteria decreased, though inter-individual difference existed. Notably, the alpha diversity of viable microbiota after freezing did not change significantly, while its composition changed. Freezing significantly reduced the viable bacteria in Gram-negative genera of Bacteroidetes and Firmicutes, and proportionally increased Gram-positive bacteria in genera of Actinobacteria and Firmicutes, including Bifidobacterium, Collinsella and Blautia, implying that the cell envelope structure associated with the bacterial sensitivity to freezing. On the contrary, the room temperature storage not only decreased the number of viable bacteria, but also decreased the microbial alpha diversity, and remarkably enriched facultative anaerobes of Escherichia-Shigella, Enterococcus and Lactococcus, some of which are opportunistic pathogens. Our findings suggested that changes in viable microbiota in stool samples caused by cryopreservation should be paid enough attention for downstream utilization.
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http://dx.doi.org/10.1007/s00203-022-03169-1DOI Listing
August 2022

Case report: Compound heterozygous mutations in the gene cause progressive keratodermia and thrombocytopenia.

Front Pediatr 2022 26;10:940618. Epub 2022 Jul 26.

Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

KDSR (3-ketodihydrosphingosine reductase) is a short-chain dehydrogenase located in the endoplasmic reticulum. Mutations in KDSR cause defects in ceramides, which play a key role in the biological processes of the skin and other tissues. Herein, we report a case of compound heterozygous mutations in that caused progressive keratodermia and thrombocytopenia in a 2-year-old male patient.
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http://dx.doi.org/10.3389/fped.2022.940618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360485PMC
July 2022

Evaluation of a Most Probable Number Method for Detection and Quantification of .

Pathogens 2022 Jul 12;11(7). Epub 2022 Jul 12.

Institute for Environmental Health, Beijing Center for Disease Prevention and Control, Beijing 100013, China.

The detection and enumeration of () in water is crucial for water quality management, human health and has been a research hotspot worldwide. Due to the time-consuming and complicated operation of the plate culture method, it is necessary to adopt a fast and effective method for application. The present study aimed to comprehensively evaluate the performance and applicability of the MPN method by comparing its qualitative and quantitative results with the GB/T 18204.5-2013 and ISO methods, respectively. The qualitative results showed that 372 samples (53%) were negative for both methods; 315 samples (45%) were positively determined by the MPN method, compared with 211 samples (30%) using GB/T 18204.5-2013. The difference in the detection rate between the two methods was statistically significant. In addition, the quantitative results showed that the concentration of by the MPN method was greater than ISO 11731 and the difference was statistically significant. However, the two methods were different but highly correlated (r = 0.965, < 0.001). The specificity and sensitivity of the MPN method were 89.85% and 95.73%, respectively. Overall, the results demonstrated that the MPN method has higher sensitivity, a simple operation process and good application prospects in the routine monitoring of from water samples.
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http://dx.doi.org/10.3390/pathogens11070789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324539PMC
July 2022

Comparing human milk macronutrients measured using analyzers based on mid-infrared spectroscopy and ultrasound and the application of machine learning in data fitting.

BMC Pregnancy Childbirth 2022 Jul 14;22(1):562. Epub 2022 Jul 14.

Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.

Objective: Fat, carbohydrates (mainly lactose) and protein in breast milk all provide indispensable benefits for the growth of newborns. The only source of nutrition in early infancy is breast milk, so the energy of breast milk is also crucial to the growth of infants. Some macronutrients composition in human breast milk varies greatly, which could affect its nutritional fulfillment to preterm infant needs. Therefore, rapid analysis of macronutrients (including lactose, fat and protein) and milk energy in breast milk is of clinical importance. This study compared the macronutrients results of a mid-infrared (MIR) analyzer and an ultrasound-based breast milk analyzer and unified the results by machine learning.

Methods: This cross-sectional study included breastfeeding mothers aged 22-40 enrolled between November 2019 and February 2021. Breast milk samples (n = 546) were collected from 244 mothers (from Day 1 to Day 1086 postpartum). A MIR milk analyzer (BETTERREN Co., HMIR-05, SH, CHINA) and an ultrasonic milk analyzer (Honɡyanɡ Co,. HMA 3000, Hebei, CHINA) were used to determine the human milk macronutrient composition. A total of 465 samples completed the tests in both analyzers. The results of the ultrasonic method were mathematically converted using machine learning, while the Bland-Altman method was used to determine the limits of agreement (LOA) between the adjusted results of the ultrasonic method and MIR results.

Results: The MIR and ultrasonic milk analyzer results were significantly different. The protein, fat, and energy determined using the MIR method were higher than those determined by the ultrasonic method, while lactose determined by the MIR method were lower (all p < 0.05). The consistency between the measured MIR and the adjusted ultrasound values was evaluated using the Bland-Altman analysis and the scatter diagram was generated to calculate the 95% LOA. After adjustments, 93.96% protein points (436 out of 465), 94.41% fat points (439 out of 465), 95.91% lactose points (446 out of 465) and 94.62% energy points (440 out of 465) were within the LOA range. The 95% LOA of protein, fat, lactose and energy were - 0.6 to 0.6 g/dl, -0.92 to 0.92 g/dl, -0.88 to 0.88 g/dl and - 40.2 to 40.4 kj/dl, respectively and clinically acceptable. The adjusted ultrasonic results were consistent with the MIR results, and LOA results were high (close to 95%).

Conclusions: While the results of the breast milk rapid analyzers using the two methods varied significantly, they could still be considered comparable after data adjustments using linear regression algorithm in machine learning. Machine learning methods can play a role in data fitting using different analyzers.
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http://dx.doi.org/10.1186/s12884-022-04891-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284806PMC
July 2022

A critical review on interaction of microplastics with organic contaminants in soil and their ecological risks on soil organisms.

Chemosphere 2022 Jul 4;306:135573. Epub 2022 Jul 4.

Beijing Key Lab for Source Control Technology of Water Pollution, College of Environmental Science and Engineering, Beijing Forestry University, Beijing, 100083, China; Engineering Research Center for Water Pollution Source Control & Eco-remediation, College of Environmental Science and Engineering, Beijing Forestry University, Beijing, 100083, China. Electronic address:

The pollution of microplastics (MPs) in soil has become a global environmental problem. Due to high sorption capacity and persistence in environment, the MPs exhibit combined effects with organic pollutants in soil, thereby posing a potential risk to soil ecology and human health. However, limited reviews are available on this subject. Therefore, in response to this issue, this review provides an in-depth account of interaction of MPs with organic contaminants in soil and the combined risks to soil environment. The sorption of organic contaminants onto MPs is mainly through hydrophobic and π-π interactions, hydrogen bonding, pore filling and electrostatic and van der Waals forces. The intrinsic characteristics of MPs, organic contaminants and soil are the key factors influencing the sorption of organic pollutants onto MPs. Importantly, the presence of MPs changes the sorption, degradation and transport behaviors of organic contaminants in soil, and affects the toxic effects of organic contaminants on soil organisms including animals, plants and soil microorganisms through synergistic or antagonistic effects. Source control, policy implementation and plastic removal are the main preventive and control measures to reduce soil MPs pollution. Finally, priorities for future research are proposed, such as field investigations of co-pollution, contribution of plastisphere to organic contaminant degradation, and mechanisms of MPs effects on organic contaminant toxicity.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135573DOI Listing
July 2022

Lymph Node Ratio Improves Prediction of Overall Survival in Esophageal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy: A National Cancer Database Analysis.

Ann Surg 2022 Jul 6. Epub 2022 Jul 6.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objective: This study aimed to propose a revised ypN (r-ypN) classification based on lymph node ratio (LNR) and to examine its prognostic value in postneoadjuvant esophageal cancer.

Background: A new postneoadjuvant pathologic (ypTNM) staging classification has been introduced for esophageal cancer. However, the ypN classification currently defined by the number of positive lymph nodes is influenced by the extent of lymphadenectomy.

Methods: Data on 7195 esophageal cancer patients receiving neoadjuvant chemoradiation were extracted from the National Cancer Database (NCDB). Four r-ypN stages were defined by 3 LNR thresholds (0%, 10%, and 20% using X-tile software). A revised ypTNM (r-ypTNM) classification was developed by solely changing N categories. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Akaike information criterion (AIC) and Harrell's concordance index (C-index) were used to compare the predictive performance of the current and the revised classification. External validation was performed using an independent cohort from the NEOCRTEC5010 clinical trial.

Results: Both ypN (P<0.001) and r-ypN (P<0.001) were independent prognostic factors of overall survival (OS) for esophageal cancer patients. Kaplan-Meier curves demonstrated a better discrimination with r-ypN than ypN categories. Within each ypN category (except ypN3), OS was significantly different comparing r-ypN strata; however, there were no differences between ypN strata within each r-ypN category (except r-ypN3). r-ypN (AIC: 60752 vs 60782; C-index: 0.591 vs 0.587) and r-ypTNM (AIC: 60623 vs 60628; C-index: 0.613 vs 0.610) showed better predictive performance than the current staging system, with a lower AIC (better calibration) and higher C-index (improved discrimination). This advantage was also confirmed by external validation using the NEOCRTEC5010 cohort.

Conclusions: LNR showed better performance than ypN in predicting OS of esophageal cancer patients after neoadjuvant chemoradiation and may be an improvement on the current staging system.
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http://dx.doi.org/10.1097/SLA.0000000000005450DOI Listing
July 2022

Insights into the photophysical properties of 2-(2'-hydroxyphenyl) benzazoles derivatives: Application of ESIPT mechanism on UV absorbers.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Nov 27;280:121559. Epub 2022 Jun 27.

College of Science, Northeast Forestry University, Harbin 150040, China. Electronic address:

In this present work, four novel molecules (BPN, BPNS, BPS, and BPSN), possessing excited-state intramolecular proton transfer (ESIPT) characteristics, were designed to quantify the impacts of substituent effects on their photophysical properties. By exploring the primary geometrical parameters concerning hydrogen bonds, it should be noticed that the intramolecular hydrogen bonds (IHBs) of the studied molecules have been strengthened at S state. Infrared vibrational spectra analysis illustrates that adding electron-donating group thiophene to the proton donor side can weaken the IHBs in comparison to the electron-withdrawing group pyridine. Through investigating the absorption and fluorescence spectra, it can be clearly found that the maximum absorption peaks of the studied molecules are all located in the UVA region, and their regions of fluorescence peaks are harmless to human skin. Furthermore, considering the light intensity factor, it can be concluded that BPNS is the most potential to be used as UV absorbers in the studied molecules. This work investigates the effects of the positions and types of substituent groups on photophysical properties of 2-(2'-hydroxyphenyl) benzazoles derivatives, which can help design and exploit novel UV absorbers.
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http://dx.doi.org/10.1016/j.saa.2022.121559DOI Listing
November 2022

Observation of Biradical Spin Coupling through Hydrogen Bonds.

Phys Rev Lett 2022 Jun;128(23):236401

Center for Carbon-Based Electronics and Key Laboratory for the Physics and Chemistry of Nanodevices, Department of Electronics, Peking University, Beijing 100871, China.

Investigation of intermolecular electron spin interaction is of fundamental importance in both science and technology. Here, radical pairs of all-trans retinoic acid molecules on Au(111) are created using an ultralow temperature scanning tunneling microscope. Antiferromagnetic coupling between two radicals is identified by magnetic-field-dependent spectroscopy. The measured exchange energies are from 0.1 to 1.0 meV. The biradical spin coupling is mediated through O─H⋯O hydrogen bonds, as elucidated from analysis combining density functional theory calculation and a modern version of valence bond theory.
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http://dx.doi.org/10.1103/PhysRevLett.128.236401DOI Listing
June 2022

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BMC Cancer 2022 Jun 13;22(1):650. Epub 2022 Jun 13.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.

Background: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies.

Methods: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life.

Discussion: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial.

Trial Registration: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www.

Clinicaltrials: gov/ct2/show/NCT04513418 .
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http://dx.doi.org/10.1186/s12885-022-09721-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190085PMC
June 2022

Robotic versus thoracoscopic combined anatomic subsegmentectomy for early-stage lung cancer: early results of a cohort study.

J Thorac Dis 2022 May;14(5):1441-1449

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Combined anatomic subsegmentectomy performed by video-assisted thoracic surgery or robot-assisted thoracic surgery is an emerging minimally invasive surgical technique for patients with early-stage non-small cell lung cancer (NSCLC). However, the early results of these two methods have barely been studied.

Methods: A retrospective analysis of medical records from Shanghai Ruijin Hospital between July 2017 and August 2021 included 62 patients, 32 of whom underwent video-assisted combined anatomic pulmonary subsegmentectomy and 30 underwent robot-assisted combined anatomic pulmonary subsegmentectomy. Perioperative outcomes were compared.

Results: Sixty-two patients with comparable baseline characteristics were included in this study. No significant difference was found in the length of postoperative hospital stay, operation duration, intraoperative blood loss and the rate of overall complications between the robot-assisted and video-assisted groups. A higher cost was observed in the robot-assisted group compared to the video-assisted group. There were more N1 lymph nodes and N1 stations dissected in the robot-assisted group compared with the video-assisted group; the same results were observed with regard to the number of N2 lymph nodes and N2 stations dissected.

Conclusions: It is safe and feasible for the patients with early-stage NSCLC to be treated with combined anatomic subsegmentectomy performed via robot-assisted or video-assisted thoracic surgery. The robotic approach may contribute to the potential improvements in N1 and N2 lymph node retrieval.
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http://dx.doi.org/10.21037/jtd-21-1895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186238PMC
May 2022

Pulmonary Infection Due to Reactivation of Latent Epstein-Barr Virus in a Patient With Crohn's Disease Treated With Infliximab.

Inflamm Bowel Dis 2022 06;28(6):e80-e81

Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China.

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http://dx.doi.org/10.1093/ibd/izab304DOI Listing
June 2022

Designing Cu as a Partial Substitution of Protons in Polyaniline Emeraldine Salt: Room-Temperature-Recoverable HS Sensing Properties and Mechanism Study.

ACS Appl Mater Interfaces 2022 Jun 2. Epub 2022 Jun 2.

State Key Laboratory of Electronic Thin Films and Integrated Devices, School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China (UESTC), Chengdu 610054, P. R. China.

Hydrogen sulfide (HS) sensors are in urgent demand in the field of hermetic environment detection and metabolic disease diagnosis. However, most of the reported room-temperature (RT) HS sensors based on transition metal oxides/salts unavoidably suffer from the poisoning effect, resulting in the unrecoverable behavior to restrain their application. Herein, copper(II) chloride-doped polyaniline emeraldine salt (PANI-CuCl) was devised for RT-recoverable HS detection, where the copper ion (Cu) was designed as a partial substitution of protons (H) in PANI. The prepared gas sensor exhibited full recovery capability toward 0.25-10 ppm HS, good repeatability, and long-term stability under 80% RH. Meanwhile, the changes of the PANI-CuCl during the HS sensing period were analyzed via multiple analytical methods to reveal the reversible sensing behavior. Results showed that doping of Cu not only promoted the PANI's response through the formation of conductive copper sulfide (CuS) and following H redoping in the PANI but also facilitated the sensor's recovery behavior because of the Cu regeneration under the H/oxygen environment. This work not only proves the changes of the interaction between the PANI and Cu during the HS sensing period but also sheds light on designing recoverable HS sensors based on transition metal salts.
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http://dx.doi.org/10.1021/acsami.2c05863DOI Listing
June 2022

Uncertainties of soil organic carbon stock estimation caused by paleoclimate and human footprint on the Qinghai Plateau.

Carbon Balance Manag 2022 May 26;17(1). Epub 2022 May 26.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, No. 19 XinJieKouWai St., HaiDian District, Beijing, 100875, China.

Background: Quantifying the stock of soil organic carbon (SOC) and evaluating its potential impact factors is important to evaluating global climate change. Human disturbances and past climate are known to influence the rates of carbon fixation, soil physiochemical properties, soil microbial diversity and plant functional traits, which ultimately affect the current SOC storage. However, whether and how the paleoclimate and human disturbances affect the distribution of SOC storage on the high-altitude Tibetan Plateau remain largely unknown. Here, we took the Qinghai Plateau, the main component of the Tibetan Plateau, as our study region and applied three machine learning models (random forest, gradient boosting machine and support vector machine) to estimate the spatial and vertical distributions of the SOC stock and then evaluated the effects of the paleoclimate during the Last Glacial Maximum and the mid-Holocene periods as well as the human footprint on SOC stock at 0 to 200 cm depth by synthesizing 827 soil observations and 71 environmental factors.

Results: Our results indicate that the vegetation and modern climate are the determinant factors of SOC stocks, while paleoclimate (i.e., paleotemperature and paleoprecipitation) is more important than modern temperature, modern precipitation and the human footprint in shaping current SOC stock distributions. Specifically, the SOC stock was deeply underestimated in near natural ecosystems and overestimated in the strongly human disturbance ecosystems if the model did not consider the paleoclimate. Overall, the total SOC stock of the Qinghai Plateau was underestimated by 4.69%, 12.25% and 6.67% at depths of 0 to 100 cm, 100 to 200 cm and 0 to 200 cm, respectively. In addition, the human footprint had a weak influence on the distributions of the SOC stock. We finally estimated that the total and mean SOC stock at 200 cm depth by including the paleoclimate effects was 11.36 Pg C and 16.31 kg C m, respectively, and nearly 40% SOC was distributed in the top 30 cm.

Conclusion: The paleoclimate is relatively important for the accurate modeling of current SOC stocks. Overall, our study provides a benchmark for predicting SOC stock patterns at depth and emphasizes that terrestrial carbon cycle models should incorporate information on how the paleoclimate has influenced SOC stocks.
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http://dx.doi.org/10.1186/s13021-022-00203-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134640PMC
May 2022

Considerations for the Surgical Management of Thoracic Cancers During the COVID-19 Pandemic: Rational Strategies for Thoracic Surgeons.

Front Surg 2022 9;9:742007. Epub 2022 May 9.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: The novel Coronavirus Disease 2019 (COVID-19) has resulted in a global health crisis since first case was identified in December 2019. As the pandemic continues to strain global public health systems, elective surgeries for thoracic cancer, such as early-stage lung cancer and esophageal cancer (EC), have been postponed due to a shortage of medical resources and the risk of nosocomial transmission. This review is aimed to discuss the influence of COVID-19 on thoracic surgical practice, prevention of nosocomial transmission during the pandemic, and propose modifications to the standard practices in the surgical management of different thoracic cancer.

Methods: A literature search of PubMed, Medline, and Google Scholar was performed for articles focusing on COVID-19, early-stage lung cancer, and EC prior to 1 July 2021. The evidence from articles was combined with our data and experience.

Results: We review the challenges in the management of different thoracic cancer from the perspectives of thoracic surgeons and propose rational strategies for the diagnosis and treatment of early-stage lung cancer and EC during the COVID-19 pandemic.

Conclusions: During the COVID-19 pandemic, the optimization of hospital systems and medical resources is to fight against COVID-19. Indolent early lung cancers, such as pure ground-glass nodules/opacities (GGOs), can be postponed with a lower risk of progression, while selective surgeries of more biologically aggressive tumors should be prioritized. As for EC, we recommend immediate or prioritized surgeries for patients with stage Ib or more advanced stage and patients after neoadjuvant therapy. Routine COVID-19 screening should be performed preoperatively before thoracic surgeries. Prevention of nosocomial transmission by providing appropriate personal protective equipment (PPE), such as N-95 respirator masks with eye protection to healthcare workers, is necessary.
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http://dx.doi.org/10.3389/fsurg.2022.742007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124784PMC
May 2022

An ACTH-secreting tumor hidden in a congenitally hypoplastic left lung.

Interact Cardiovasc Thorac Surg 2022 May 16. Epub 2022 May 16.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Huangpu District, Shanghai, (200025, ), P.R. China.

Ectopic ACTH syndrome(EAS) has historically been a therapeutic challenge because of difficulty localizing occult ACTH-secreting tumors. Here we report a case of a 67-year-old woman with EAS and had an ACTH-secreting tumour hidden within a congenitally hypoplastic left lung. A satisfactory therapeutic outcome was obtained after left pneumonectomy was performed on patient in this case.
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http://dx.doi.org/10.1093/icvts/ivac130DOI Listing
May 2022

Theoretical Study on the Atom-Substituted Quinazoline Derivatives with Faint Emission as Potential Sunscreens.

ACS Omega 2022 May 22;7(17):14848-14855. Epub 2022 Apr 22.

College of Science, Northeast Forestry University, Harbin, Heilongjiang 150040, China.

Two novel compounds (HQS and HQSe) with excited-state intramolecular proton transfer (ESIPT) properties were designed based on the compound 2-(2-hydroxy-3-ethoxyphenyl)-3-quinazolin-4-one (HQ). The parameters related to the ESIPT properties and electronic spectra of HQ and its derivatives were calculated using density functional theory and time-dependent density functional theory methods. The obtained geometric configurations, infrared vibrational spectra, and reduced density gradient scatter plots have shown that the intramolecular hydrogen bond O···H-N has been weakened upon photoexcitation. Moreover, from the scanned potential energy curves, it can be found that the ESIPT processes of the three compounds have no energy barriers. It is noteworthy that HQS and HQSe can strongly absorb light in the UVA region (∼340 nm) and exhibit weak fluorescence emission in the visible light region, which comes from the keto configuration. The special optical properties of HQS and HQSe can promote their application as potential sunscreen agents.
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http://dx.doi.org/10.1021/acsomega.2c00316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088953PMC
May 2022

Interactive Effects of Endophytes and Arbuscular Mycorrhizal Fungi on Saline-Alkali Stress Tolerance in Tall Fescue.

Front Microbiol 2022 25;13:855890. Epub 2022 Apr 25.

College of Life Sciences, Dezhou University, Dezhou, China.

endophytes and arbuscular mycorrhizal fungi (AMFs) are two important symbiotic microorganisms of tall fescue (). Our research explores the combined effects of endophytes and AMF on saline-alkali stress. The finding revealed that a significant interaction between endophytes and AMF, and saline-alkali stress occurred in the growth and physiological parameters of tall fescue. Endophyte infection significantly enhanced tall fescue resistance to saline-alkali stress by increasing shoot and root biomass and nutrient uptake (organic carbon, total nitrogen, and total phosphorus concentration), and accumulating K while decreasing Na concentration. Furthermore, the beneficial effect of endophytes was enhanced by the beneficial AMF, (CE) but was reduced by the detrimental AMF, (FM). Our findings highlight the importance of interactions among multiple microorganisms for plant performance under saline-alkali stress.
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http://dx.doi.org/10.3389/fmicb.2022.855890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083001PMC
April 2022

Spatiotemporal correlations between water quality and microbial community of typical inflow river into Taihu Lake, China.

Environ Sci Pollut Res Int 2022 Apr 23. Epub 2022 Apr 23.

Institute of Environmental Pollution Control and Treatment, Zhejiang University, Hangzhou, 310058, China.

Changxing River, which is a typical inflow river into Taihu Lake and occurs severe algae invasion, is selected to study the effect of different pollution sources on the water quality and ecological system. Four types of pollution sources, including the estuary of Taihu Lake, discharge outlets of urban wastewater treatment plants, stormwater outlets, and nonpoint source agricultural drainage areas, were chosen, and next-generation sequencing and multivariate statistical analyses were used to characterize the microbial communities and reveal their relationship with water physicochemical properties. The results showed that ammonia nitrogen (NH-N), total nitrogen (TN), and total phosphorus (TP) were the main pollutants in Changxing River, especially at stormwater outlets. At the same time, the diversity of microbial communities was the highest in the summer, and dominant microbes included Proteobacteria (40.9%), Bacteroidetes (21.0%), and Euryarchaeota (6.1%). The results of BIOENV analysis showed that the major seasonal differences in the diversity of microbial community of Changxing river were explained by the combination of water temperature (T), air pressure (P), TP, and COD. From the perspective of different pollution types, relative abundances of Microcystis and Nostocaceae at the estuary of Taihu Lake were correlated positively with dissolved oxygen (DO) and pH, and relative abundances of Pseudomonas and Arcobacter were correlated positively with concentrations of TN and nitrate nitrogen (NO-N) at stormwater outlets. This study provided a reference for the impact of pollution types on river microbial ecosystem under complex hydrological conditions and guidance for the selection of restoration techniques for polluted rivers entering the important lake.
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http://dx.doi.org/10.1007/s11356-022-19023-2DOI Listing
April 2022

The Frequency Effect of the Motor Imagery Brain Computer Interface Training on Cortical Response in Healthy Subjects: A Randomized Clinical Trial of Functional Near-Infrared Spectroscopy Study.

Front Neurosci 2022 31;16:810553. Epub 2022 Mar 31.

Department of Rehabilitation, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: The motor imagery brain computer interface (MI-BCI) is now available in a commercial product for clinical rehabilitation. However, MI-BCI is still a relatively new technology for commercial rehabilitation application and there is limited prior work on the frequency effect. The MI-BCI has become a commercial product for clinical neurological rehabilitation, such as rehabilitation for upper limb motor dysfunction after stroke. However, the formulation of clinical rehabilitation programs for MI-BCI is lack of scientific and standardized guidance, especially limited prior work on the frequency effect. Therefore, this study aims at clarifying how frequency effects on MI-BCI training for the plasticity of the central nervous system.

Methods: Sixteen young healthy subjects (aged 22.94 ± 3.86 years) were enrolled in this randomized clinical trial study. Subjects were randomly assigned to a high frequency group (HF group) and low frequency group (LF group). The HF group performed MI-BCI training once per day while the LF group performed once every other day. All subjects performed 10 sessions of MI-BCI training. functional near-infrared spectroscopy (fNIRS) measurement, Wolf Motor Function Test (WMFT) and brain computer interface (BCI) performance were assessed at baseline, mid-assessment (after completion of five BCI training sessions), and post-assessment (after completion of 10 BCI training sessions).

Results: The results from the two-way ANOVA of beta values indicated that GROUP, TIME, and GROUP × TIME interaction of the right primary sensorimotor cortex had significant main effects [GROUP: = 7.251, = 0.010; TIME: = 3.317, = 0.046; GROUP × TIME: = 5.676, = 0.007]. The degree of activation was affected by training frequency, evaluation time point and interaction. The activation of left primary sensory motor cortex was also affected by group (frequency) ( = 0.003). Moreover, the TIME variable was only significantly different in the HF group, in which the beta value of the mid-assessment was higher than that of both the baseline assessment ( = 0.027) and post-assessment ( = 0.001), respectively. Nevertheless, there was no significant difference in the results of WMFT between HF group and LF group.

Conclusion: The major results showed that more cortical activation and better BCI performance were found in the HF group relative to the LF group. Moreover, the within-group results also showed more cortical activation after five sessions of BCI training and better BCI performance after 10 sessions in the HF group, but no similar effects were found in the LF group. This pilot study provided an essential reference for the formulation of clinical programs for MI-BCI training in improvement for upper limb dysfunction.
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http://dx.doi.org/10.3389/fnins.2022.810553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008330PMC
March 2022

Edge-enriched MoS nanosheets modified porous nanosheet-assembled hierarchical InO microflowers for room temperature detection of NO with ultrahigh sensitivity and selectivity.

J Hazard Mater 2022 07 11;434:128836. Epub 2022 Apr 11.

State Key Laboratory of Electronic Thin Films and Integrated Devices, School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China (UESTC), Chengdu 610054, PR China. Electronic address:

Nitrogen dioxide (NO) is one of the most hazardous toxic pollutants to human health and the environment. However, deficiencies of low sensitivity and poor selectivity at room temperature (RT) restrain the application of NO sensors. Herein, the edge-enriched MoS nanosheets modified porous nanosheets-assembled three-dimensional (3D) InO microflowers have been synthesized to improve the sensitivity and selectivity of NO detection at RT. The results show that the InO/MoS composite sensor exhibits a response as high as 343.09-5 ppm NO, which is 309 and 72.5 times higher than the sensors based on the pristine MoS and InO. The composite sensor also shows short recovery time (37 s), excellent repeatability and long-term stability. Furthermore, the response of the InO/MoS sensor to NO is at least 30 times higher than that of other gases, proving the ultrahigh selectivity of the sensor. The outstanding sensing performance of the InO/MoS sensor can be attributed to the synergistic effect and abundant active sites originating from the p-n heterojunction, exposed edge structures and the designed 2D/3D hybrid structure. The strategy proposed herein is expected to provide a useful reference for the development of high-performance RT NO sensors.
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http://dx.doi.org/10.1016/j.jhazmat.2022.128836DOI Listing
July 2022

Electrogenerated chemiluminescence biosensor for microRNA detection incorporating enzyme-free dual DNA cyclic amplification and Ru(bpy)-functionalized metal-organic framework.

Talanta 2022 Aug 6;245:123458. Epub 2022 Apr 6.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, PR China. Electronic address:

Herein, a novel electrogenerated chemiluminescence (ECL) biosensor for the determination of microRNA was developed on the basis of enzyme-free dual signal amplification and Ru(bpy)-functionalized metal-organic frameworks ([email protected](Al)-NH) as ECL signal labels. MicroRNA-21 (miRNA-21) was used as a model target, which initiated the toehold-mediated strand displacement reaction (TSDR). The first cyclic amplification TSDR converted a small quantify of miRNA-21 to abundant report strands (RS), which then catalyzed the second cyclic amplification catalytic hairpin assembly (CHA). The CHA ran cyclically to produce numerous H1-H2 duplexes with the exposed segment. Finally, the newly exposed segment of H2 could bind with the ECL probe ([email protected](Al)-NH), leading to an evident ECL signal enhancement. The results showed that the ECL intensity varied linearly with the logarithm of the concentration of miRNA-21 ranging from 0.01 to 10,000 pM. The detection limit was as low as 4 fM because of the signal amplification through TSDR and CHA processes coupling with [email protected](Al)-NH. In addition, this biosensor has been successfully applied to detect miRNA-21 in MCF-7 cells, providing great potential for the related clinical diagnosis.
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http://dx.doi.org/10.1016/j.talanta.2022.123458DOI Listing
August 2022

1α,25-Dihydroxyvitamin D3 Promotes Angiogenesis After Cerebral Ischemia Injury in Rats by Upregulating the TGF-β/Smad2/3 Signaling Pathway.

Front Cardiovasc Med 2022 16;9:769717. Epub 2022 Mar 16.

Department of Neurology II, The Affiliated Hospital of Weifang Medical University, Weifang, China.

Stroke is a disease with high morbidity, disability and mortality, which seriously endangers the life span and quality of life of people worldwide. Angiogenesis and neuroprotection are the key to the functional recovery of penumbra function after acute cerebral infarction. In this study, we used the middle cerebral artery occlusion (MCAO) model to investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25-D3) on transforming growth factor-β (TGF-β)/Smad2/3 signaling pathway. Cerebral infarct volume was measured by TTC staining. A laser speckle flow imaging system was used to measure cerebral blood flow (CBF) around the ischemic cortex of the infarction, followed by platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and isolectin-B4 (IB4) immunofluorescence. The expression of vitamin D receptor (VDR), TGF-β, Smad2/3, p-Smad2, p-Smad3, and vascular endothelial growth factor (VEGF) was analyzed by western blot and RT-qPCR. Results showed that compared with the sham group, the cerebral infarction volume was significantly increased while the CBF was reduced remarkably in the MCAO group. 1,25-D3 reduced cerebral infarction volume, increased the recovery of CBF and expressions of VDR, TGF-β, p-Smad2, p-Smad3, and VEGF, significantly increased IB4 tip cells and CD31 vascular length in the peri-infarct area compared with the DMSO group. The VDR antagonist pyridoxal-5-phosphate (P5P) partially reversed the neuroprotective effects of 1,25-D3 described above. In summary, 1,25-D3 plays a neuroprotective role in stroke by activating VDR and promoting the activation of TGF-β, which in turn up-regulates the TGF-β/Smad2/3 signaling pathway, increases the release of VEGF and thus promotes angiogenesis, suggesting that this signaling pathway may be an effective target for ischemic stroke treatment. 1,25-D3 is considered to be a neuroprotective agent and is expected to be an effective drug for the treatment of ischemic stroke and related diseases.
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http://dx.doi.org/10.3389/fcvm.2022.769717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966232PMC
March 2022

The Role of Entropy Gains in the Exciton Separation in Organic Solar Cells.

Macromol Rapid Commun 2022 Mar 26:e2100903. Epub 2022 Mar 26.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.

In organic solar cells (OSCs), the lower dielectric constant of organic semiconductor material induces a strong Coulomb attraction between electron-hole pairs, which leads to a low exciton separation efficiency, especially the charge transfer (CT) state. The CT state formed at the electron-donor (D) and electron-acceptor (A) interface is regarded as an unfavorable property of organic photovoltaic devices. Since the OSC works in a nonzero temperature condition, the entropy effect would be one of the main reasons to overcome the Coulomb energy barrier and must be taken into account. In this review, the present understanding of the entropy-driven charge separation is reviewed and how factors such as the dimensionality of the organic semiconductor, energy disorder effect, the morphology of the active layer, are described, as well as how the nonequilibrium effect affects the entropy contribution in compensating the Coulomb dissociation barrier for CT exciton separation and charge generation process. The investigation of the entropy effect on exciton dissociation mechanism from both theoretical and experimental aspects is focused on, which provides pathways for understanding the underlying mechanisms of exciton separation and further enhancing the efficiency of OSCs.
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http://dx.doi.org/10.1002/marc.202100903DOI Listing
March 2022

Alignment of Organic Conjugated Molecules for High-Performance Device Applications.

Macromol Rapid Commun 2022 Jul 1;43(14):e2100931. Epub 2022 May 1.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.

High-performance organic semiconductor materials as the electroactive components of optoelectronic devices have attracted much attention and made them ideal candidates for solution-processable, large-area, and low-cost flexible electronics. Especially, organic field-effect transistors (OFETs) based on conjugated semiconductor materials have experienced stunning progress in device performance. To make these materials economically viable, comprehensive knowledge of charge transport mechanisms is required. The alignment of organic conjugated molecules in the active layer is vital to charge transport properties of devices. The present review highlights the recent progress of processing-structure-transport correlations that allow the precise and uniform alignment of organic conjugated molecules over large areas for multiple electronic applications, including OFETs, organic thermoelectric devices (OTEs), and organic phototransistors (OPTs). Different strategies for regulating crystallinity and macroscopic orientation of conjugated molecules are introduced to correlate the molecular packing, the device performance, and charge transport anisotropy in multiple organic electronic devices.
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http://dx.doi.org/10.1002/marc.202100931DOI Listing
July 2022

Multifaceted tannin crosslinked bioinspired dECM decorated nanofibers modulating cell-scaffold biointerface for tympanic membrane perforation bioengineering.

Biomed Mater 2022 04 7;17(3). Epub 2022 Apr 7.

School of Nano-Tech and Nano-Bionics, University of Science and Technology of China (USTC), Hefei 230026, People's Republic of China.

Tympanic membrane (TM) perforation leads to persistent otitis media, conductive deafness, and affects life quality. Ointment medication may not be sufficient to treat TM perforation (TMP) due to the lack of an underlying tissue matrix and thus requiring a scaffold-based application. The engineering of scaffold biointerface close to the matrix via tissue-specific decellularized extracellular matrix (dECM) is crucial in instructing cell behaviour and regulating cell-material interaction in the bioengineering domain. Herein, polycaprolactone (PCL) and TM-dECM (from Sprague-Dawley rats) were combined in a different ratio in nanofibrous form using an electrospinning process and crosslinked via tannic acid. The histological and biochemical assays demonstrated that chemical and enzymatic decellularization steps removed cellular/immunogenic contents while retaining collagen and glycosaminoglycan. The morphological, physicochemical, thermomechanical, contact angle, and surface chemical studies demonstrated that the tannin crosslinked PCL/dECM nanofibers fine-tune biophysical and biochemical properties. The multifaceted crosslinked nanofibers hold the tunable distribution of dECM moieties, assembled into a spool-shaped membrane, and could easily insert into perforated sites. The dECM decorated fibers provide a preferable biomimetic matrix for L929 fibroblast adhesion, proliferation, matrix adsorption, and f-actin saturation, which could be crucial for bioengineering. Overall, dECM patterning, surface hydrophilicity, interconnected microporosities, and multifaceted nanofibrous biosystem modulate cell-scaffold performance and could open opportunities to reconstruct TMP in a biomimetic fashion.
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http://dx.doi.org/10.1088/1748-605X/ac6125DOI Listing
April 2022

Targeting Lipid Rafts as a Rapid Screening Strategy for Potential Antiadipogenic Polyphenols along with the Structure-Activity Relationship and Mechanism Elucidation.

J Agric Food Chem 2022 Mar 18;70(12):3872-3885. Epub 2022 Mar 18.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Obesity is a global public health problem that endangers human health, and a rapid search for compounds with antiadipogenic activity could provide solutions to overcome this problem. Polyphenols are potential antiadipogenic compounds, but the screening strategy, structure-activity relationship (SAR), and elucidation of their mechanisms of action remain poorly understood because of the high diversity of polyphenols. Lipid rafts, enriched with sphingolipids and cholesterol, are considered a potential target of polyphenols for the regulation of cellular processes and diseases. Here, a novel rapid screening active polyphenol strategy that targets the lipid rafts using molecular dynamic simulation was developed and validated by 3T3-L1 preadipocyte assay. The screening strategy is high-throughput, inexpensive, reagent-free, and effort saving. In addition, the SAR and mechanisms of action mediating the differentiation-inhibition of the preadipocyte by polyphenols were well elucidated by utilizing multiple technologies, such as "raft-like liposomes" systems, giant plasma membrane vesicles, noninvasive lipid raft probes, and ultrahigh-resolution microscopy. High inhibitory-activity polyphenols could penetrate deeper into the hydrophobic lipid center, in an inverted V-shaped manner or by insertion of galloyl groups into rafts, thus disrupting the ordered domain of lipid rafts. In contrast, the medium and low inhibitory-activity polyphenols could only localize on the surface of lipid rafts, exerting slight and the weakest interference with a lipid raft structure, respectively. The combined use of reliable technologies could yield new knowledge on the SAR and the molecular mechanisms of polyphenols.
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http://dx.doi.org/10.1021/acs.jafc.2c00444DOI Listing
March 2022

Chronic intermittent hypoxia induces gut microbial dysbiosis and infers metabolic dysfunction in mice.

Sleep Med 2022 03 16;91:84-92. Epub 2022 Feb 16.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background And Objectives: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, and has been associated with adverse metabolic outcomes. There is increasing evidence indicating the important role of gut microbiota in OSA and its comorbidities, while the perturbation of intestinal microbial community elicited by OSA has yet to be well-characterized. Here, we investigated the effect of chronic intermittent hypoxia (IH), a hallmark feature of OSA, on gut microbiota in mice.

Methods: Male C57BL/6 mice were exposed to a pattern of chronic IH or normoxic conditions for 6 weeks. Fecal samples were collected. The composition of microbiota was determined by 16S rRNA gene amplicon sequencing, and PICRUSt2 was performed to predict functional potential of gut microbiome.

Results: In IH mice, accompanied with elevated systemic inflammation, gut microbiota were significantly altered, characterized by enriched Bacteroides, Desulfovibrionaceae and decreased Bifidobacterium. Bacterial operational taxonomic units (OTUs) were clustered into co-abundance groups (CAGs) as potential functional unit in response to IH exposure. One CAG including bacteria of Bacteroides acidifaciens and Desulfovibrionaceae was positively correlated with systemic inflammation in mice, while another CAG composed of bacteria in Muribaculaceae was negatively correlated. Prediction of metabolic pathways showed that, changes in microbiota from IH treatment mainly impacted on bile acid and fatty acid metabolism.

Conclusion: Our data demonstrated that dysbiosis of gut microbiome was associated with systemic inflammation and metabolism disorder, and emerges as a mediator for IH and its consequences. Targeting microbiota will be a promising approach to curtail metabolic risks of OSA clinically.
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http://dx.doi.org/10.1016/j.sleep.2022.02.003DOI Listing
March 2022

Exosomal circLPAR1 functions in colorectal cancer diagnosis and tumorigenesis through suppressing BRD4 via METTL3-eIF3h interaction.

Mol Cancer 2022 02 14;21(1):49. Epub 2022 Feb 14.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.

Background: Exosomes have emerged as vital biomarkers of multiple cancers and contain abundant circular RNAs (circRNAs). However, the potential for exosomal circRNAs to be used in diagnostics and their molecular mechanism of action in colorectal cancer (CRC) remain unclear.

Methods: CRC-specific exosomal circRNAs were identified by RNA sequencing, exoRBase database and a tissue microarray. The diagnostic performance of plasma exosomal circRNAs was evaluated among cancer-free controls, precancer individuals, CRC patients, and patients with other types of cancer. The corresponding biological functions were mainly assessed using circRNA pull-down, proteomic analysis, and RNA immunoprecipitation assay underlying cellular and mouse models.

Results: CircLPAR1 was encapsulated in exosomes with high stability and detectability, and its expression in plasma exosomes was remarkably decreased during CRC development but recovered after surgery. Exosomal circLPAR1 showed cancer specificity in CRC diagnosis and increased the diagnostic performance to an area under the receiver operating characteristic curve of 0.875, as determined by analysing its performance in combination with common clinical biomarkers CEA and CA19-9. Additionally, circLPAR1 was downregulated in CRC tissues and was associated with overall survival. Mechanistically, exosomal circLPAR1 was internalized by CRC cells, and it suppressed tumor growth, likely because exosomal circLPAR1 directly bound with eIF3h specifically suppressed the METTL3-eIF3h interaction, decreasing the translation of oncogene BRD4.

Conclusions: This comprehensive study highlights plasma exosomal circLPAR1 as a promising predictor in CRC diagnosis and describes its biological regulation of colorectal tumorigenesis. This study provides a new perspective on early diagnosis in the clinic and pathogenesis in disease development.
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http://dx.doi.org/10.1186/s12943-021-01471-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842935PMC
February 2022

A low-swelling and toughened adhesive hydrogel with anti-microbial and hemostatic capacities for wound healing.

J Mater Chem B 2022 02 9;10(6):915-926. Epub 2022 Feb 9.

CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

Hydrogel-based wound dressings with tissue adhesion abilities are widely used for wound closure. However, currently developed hydrogel adhesives are still poor at continuing to seal wounds while bleeding is ongoing. Herein, we demonstrate an antibacterial and hemostatic hydrogel adhesive with low-swelling properties and toughness for wound healing. The hydrogel was composed of Pluronic F127 diacrylate, quaternized chitosan diacrylate, silk fibroin, and tannic acid, and it was not only able to maintain good tissue adhesion abilities in a moist environment but it also showed guaranteed tissue adhesion and mechanical strength after absorbing water due to its low-swelling and toughness properties. Furthermore, and tests demonstrated that the hydrogel also had antibacterial, antioxidant, and hemostatic properties, which could promote tissue regeneration. All these findings demonstrate that this hydrogel with multifunctional properties is a promising material for clinical wound healing applications.
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http://dx.doi.org/10.1039/d1tb01871jDOI Listing
February 2022

Purification and characterization of a novel thermostable anticoagulant protein from medicinal leech Whitmania pigra Whitman.

J Ethnopharmacol 2022 Apr 13;288:114990. Epub 2022 Jan 13.

Department of Chinese Materia Medica and Pharmacy, School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China. Electronic address:

Ethnopharmacological Relevance: The prevalence of cardiovascular disease (CVD) is increasing worldwide. Despite significant improvements in novel targeted treatment agents, natural products purified from medicinal animals with minimal side effects have attracted much attention. Several native proteins explored from suck-blood leeches, such as non-thermostable hirudin and its variants, revealed potent anticoagulant activity. Traditional Chinese medicine clinics have proved that non-suck-blood leech Whitmania pigra Whitman (W. pigra) also played notable roles in CVD treatments even after decoction. However, only a few natural proteins and peptides have been identified from the fresh material of this medicinal species.

Aim Of The Study: We aimed to purify and characterize thermostable anticoagulant proteins from W. pigra for further development of a therapeutic agent for thrombosis.

Materials And Methods: W. pigra crude extract was prepared by decoction in water. Anticoagulant proteins were purified by DEAE cellulose DE-52, Sephadex G-75, and reversed-phase liquid chromatography sequentially and analyzed by SDS-PAGE and LC-MS/MS for structural information. In addition, we conducted in vitro anticoagulant experiments, including plasma recalcification time (PRT) assay, fibrinolytic assay, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fib) assay, and cell viability assays. Furthermore, a carrageenan-induced chronic thromboembolism model was employed in ICR mice, and four coagulation factors (APTT, PT, TT, and Fib) activities were determined after intragastric administration.

Results: The anticoagulant protein WP-77 has a relative molecular weight of ca. 20.8 kDa. It was effective over a broad temperature range from 20 °C to 100 °C and a pH 2-8 condition. The anticoagulant activity of WP-77 was retained after incubation with pepsin but was greatly inhibited by trypsin (P < 0.01). It significantly prolonged APTT and TT (P < 0.05) but had little effect on PT and Fib in vitro. Furthermore, WP-77 of a low concentration resulted in the recovery of injured EA.hy926 by thrombin. The protein also significantly prolonged APTT and TT (P < 0.01) and inhibited thrombus formation in carrageenan-induced thrombosis mice, demonstrating its antithrombotic effect in vivo.

Conclusion: Our results suggest that WP-77 from W. pigra plays a distinct role in treating thrombotic diseases, and it is an essential substance of anticoagulant activity of non-suck-blood medicinal leeches. This thermostable anticoagulant protein could be a promising candidate for the development of clinical antithrombosis medicines.
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http://dx.doi.org/10.1016/j.jep.2022.114990DOI Listing
April 2022
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