Publications by authors named "Jian Sun"

2,466 Publications

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[Effects of BET Bromodomain Inhibitor JQ1 on Double-Expressor Lymphoma Cell Lines and Its Mechanism].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2022 Aug;30(4):1094-1100

Department of Hematology, The Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China .E-mail:

Objective: To investigate the effects and mechanism of bromodomain and extra-terminal (BET) inhibitor JQ1 on the double-expressor lymphoma (DEL) cell lines.

Methods: Protein expressions of cMyc and BCL-2 in 3 lymphoma cell lines were checked by Western blot so as to identify DEL cell lines. CCK-8 assay was used to detect the effects of JQ1 on anti-proliferation in the DEL cell lines. Western blot and RT-PCR were used to measure the protein and mRNA expressions of cMyc, BCL-2 and BCL-6 in DEL cell lines which treated by JQ1. Flow cytometry was used to detect the effect of JQ1 on cell apoptosis.

Results: Based on the expressions of cMyc and BCL-2, the SU-DHL6 and OCILY3 cell lines were confirmed as DEL cell lines. CCK-8 assay showed that the proliferation of DEL cell lines was inhibited by JQ1, which was similar to non-DEL cell lines and mainly regulated the expression of cMyc and BCL-6 but not BCL-2. JQ1 had no effects on apoptosis in the DEL cell lines.

Conclusion: BET inhibitor JQ1 has anti-tumor effect in the DEL cell lines, thus providing evidence for the therapeutic potential of BET inhibitor JQ1.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2022.04.018DOI Listing
August 2022

Consensus of MASs With Input and Communication Delays by Predictor-Based Protocol.

IEEE Trans Cybern 2022 Aug 17;PP. Epub 2022 Aug 17.

In this article, the consensus problem of multiagent systems (MASs) affected by input and communication delays is investigated. A predictor-based state feedback protocol is used to reach the consensus of linear MASs by delay compensation. In order to analyze the maximum delay under the predictor-based protocol, the overall MASs are equivalent to the feedback interconnection system, including a linear time-invariant system and a time-delay operator, in view of the characteristic of the Laplacian matrix. Then, the maximum delay corresponding to the predictor-based protocol is evaluated by using the small gain theorem (SGT). Finally, two numerical examples are given to verify the effectiveness of the obtained consensus condition.
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http://dx.doi.org/10.1109/TCYB.2022.3192864DOI Listing
August 2022

Molecular Epidemiology of Plasmid-Mediated Types 1 and 3 Fimbriae Associated with Biofilm Formation in Multidrug Resistant Escherichia coli from Diseased Food Animals in Guangdong, China.

Microbiol Spectr 2022 Aug 15:e0250321. Epub 2022 Aug 15.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.

Types 1 and 3 fimbriae in Enterobacteriaceae play versatile roles in bacterial physiology including attachment, invasion, cell motility as well as with biofilm formation and urinary tract infections. Herein, we investigated the prevalence and transmission of plasmid-mediated types 1 and 3 fimbriae from 1753 non-duplicate Enterobacteriaceae from diseased food Animals. We identified 123 (7.01%) strong biofilm producers and all was identified as WGS analysis of 43 selected strong biofilm producers revealed that they harbored multiple ARGs, including ESBLs, PMQR and . The gene clusters and encoding types 1 and 3 fimbriae, respectively, were identified among 43 (34.96%) and 7 (5.7%) of 123 strong biofilm isolates, respectively. These two operons were able to confer strong biofilm-forming ability to an weak-biofilm forming laboratory strain. Plasmid analysis revealed that and operons were found to co-exist with ARGs and were primarily located on IncX1 and IncFII plasmids with similar backbones, respectively. operons was present in all of 9457 using archived WGS data, and shared high homology to those on plasmids of 8 replicon types and chromosomes from 6 Enterobacteriaceae species from various origins and countries. In contrast, operons was present in most of (62.15%), and shared high homology to those with only a small group of plasmids and Enterobacteriaceae species. This is the first comprehensive report of the prevalence, transmission and homology of plasmid-encoded type 1 and 3 fimbriae among the Enterobacteriaceae. Our findings indicated that plasmid-encoded and were major contributors to enhanced biofilm formation among and these two operons, in particular could be as a potential anti-biofilm target. Biofilms allow bacteria to tolerate disinfectants and antimicrobials, as well as mammalian host defenses, and are therefore difficult to treat clinically. Most research concerning biofilm-related infections is typically focused on chromosomal biofilm-associated factors, including types 1 and 3 fimbriae of biofilm-forming Enterobacterium. However, the transmission and homology of the mobile types 1 and 3 fimbriae among Enterobacteriaceae is largely unknown. The findings revealed that the plasmid-encoded type 3 fimbriae encoded by and type 1 fimbriae encoded by were major contributors to enhancing biofilm formation among strong biofilm E. coli from diseased food producing animals. Additionally, operon with high homology at an amino acid sequence was present both on plasmids of various replicon types and on chromosomes from diverse Enterobacteriaceae species from numerous origins and countries. These findings provide important information on the transmission of the mobile types 1 and 3 fimbriae among Enterobacteriaceae, indicating a potential antibiofilm target.
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http://dx.doi.org/10.1128/spectrum.02503-21DOI Listing
August 2022

Long-term outcome of combined catheter ablation and left atrial appendage closure in atrial fibrillation patients.

Int J Cardiol 2022 Aug 8. Epub 2022 Aug 8.

Department of Cardiology, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address:

Background: The combined procedure of catheter ablation and left atrial appendage closure (LAAC) aims to simultaneously control the heart rhythm and reduce the risk of strokes in patients with atrial fibrillation (AF). The study aims to evaluate the procedural safety and long-term outcome of the combined procedure in a large patient cohort.

Methods: Clinical data of AF patients who underwent the combined procedure was retrospectively analyzed. Procedural and imaging follow-up parameters were compared between the transesophageal echocardiography-guided standard process and fluoroscopy-guided modified process, and between the single-seal WATCHMAN and dual-seal LACBES devices. Long-term outcomes included all-cause mortality, thromboembolic events, major bleeding, and recurrence of atrial tachyarrhythmias.

Results: A total of 1114 patients were included. The rates of procedure-related major complications were comparable between the standard and modified processes (3.7% vs. 2.2%, p = 0.219), except for a higher incidence of respiratory depression in standard process group (0.9% vs 0%, p = 0.037), and between WATCHMAN and LACBES devices (2.4% vs. 3.3%, p = 0.535). The follow-up imaging evaluation revealed a high rate of satisfactory seals (99.7%) and a low rate of device related thrombus (1.9%), which were similar between two process groups and devices. The follow-up of over 1960 patient-years revealed low rates of mortality, thromboembolism, and nonprocedural major bleeding (1.8, 3.2, and 0.9 per 100 patient-years, respectively). Recurrent atrial tachyarrhythmias was observed in 23.9% patients.

Conclusions: The results supported the safety and long-term efficacy of the combined procedure of catheter ablation and LAAC. Fluoroscopy-guided LAAC device implantation may be considered in experienced centers.
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http://dx.doi.org/10.1016/j.ijcard.2022.08.007DOI Listing
August 2022

Retraction notice to "Exosomal microRNA-16-5p from adipose mesenchymal stem cells promotes TLR4-mediated M2 macrophage polarization in septic lung injury" [Int. Immunopharmacol. 98 (2021) 107835].

Int Immunopharmacol 2022 08 8;111:109078. Epub 2022 Aug 8.

Department of Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130021, Jilin Provence, China. Electronic address:

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http://dx.doi.org/10.1016/j.intimp.2022.109078DOI Listing
August 2022

Novel dual-reference approach facilitates the activation mapping and catheter ablation of premature atrial complexes with non-pulmonary vein and non-superior vena cava origins.

Europace 2022 Aug 9. Epub 2022 Aug 9.

Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, 200092 Shanghai, China.

Aims: Activation mapping of premature atrial complexes (PACs) proves challenging due to interference by mechanical bumping and non-targeted ectopies. This study aims to compare the mapping efficacy, instant success, and long-term recurrence of catheter ablation for PACs with non-pulmonary vein (PV) and non-superior vena cava (SVC) origins between the novel dual-reference approach (DRA) and the routine single-reference approach (SRA) of mapping.

Methods And Results: Patients with symptomatic, drug-refractory PACs, or frequent residual PACs after atrial tachyarrhythmia ablation were enrolled. During activation mapping, the coronary sinus (CS) catheter was used as the only timing reference in the SRA group. In the DRA group, another catheter, which was spatially separated from the CS catheter, was used as the second reference. The timing difference between the two references was used to discriminate the targeted PACs from the uninterested rhythms. Procedural parameters and long-term recurrence were compared. A total of 188 patients (109 in SRA and 79 in DRA) were enrolled. The baseline characteristics were similar. Compared with the SRA group, the DRA group had less repeated mapping (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.004), shorter mapping (15 ± 6 vs. 23 ± 7 min, P < 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P > 0.999), higher instant success (96.2 vs. 87.2%, P = 0.039), and lower recurrence rate (15.2 vs. 29.3%, hazard ratio 1.943, P = 0.033) during a 24-month follow-up.

Conclusion: As a novel strategy, the DRA shortens the procedural time and improves both instant and long-term success of PAC ablation, serving as a promising approach in mapping PACs with non-PV and non-SVC origins.
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http://dx.doi.org/10.1093/europace/euac129DOI Listing
August 2022

Whole tomato juice produced by a novel industrial-scale microfluidizer: Effect on physical properties and in vitro lycopene bioaccessibility.

Food Res Int 2022 Sep 30;159:111608. Epub 2022 Jun 30.

State Key Laboratory of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, China. Electronic address:

Whole tomato juice (WTJ) was prepared using a novel "industrial-scale microfluidizer system" (ISMS). The impacts of ISMS processing pressure (0-120 MPa) on the physicochemical properties and bioaccessibility of tomato juice were investigated. Increasing the processing pressure reduced the mean particle diameter (D) of the tomato juice from 151 to 30 μm, which was mainly attributed to degradation of the tomato plant cell structures by the strong disruptive forces generated by microfluidizer. Pulp sedimentation rate, precipitation weight ratio, and turbidity measurements showed that the physical stability of the tomato juice increased with increasing pressure. Indeed, ISMS-treated tomato juice remained stable for 28 days without evidence of visible layering. The lycopene concentration in the tomato juice increased from 25.0 to 28.2 μg/mL and the lycopene bioaccessibility increased from 9.0% to 14.1% after ISMS treatment. These results suggest that ISMS can improve the physical stability and nutritive value of commercial tomato juice products.
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http://dx.doi.org/10.1016/j.foodres.2022.111608DOI Listing
September 2022

Establishment and validation of a prediction model for self-absorption probability of chronic subdural hematoma.

Front Neurol 2022 22;13:913495. Epub 2022 Jul 22.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: Chronic subdural hematoma (CSDH) is common in elderly people with a clear or occult traumatic brain injury history. Surgery is a traditional method to remove the hematomas, but it carries a significant risk of recurrence and poor outcomes. Non-surgical treatment has been recently considered effective and safe for some patients with CSDH. However, it is a challenge to speculate which part of patients could obtain benefits from non-surgical treatment.

Objective: To establish and validate a new prediction model of self-absorption probability with chronic subdural hematoma.

Method: The prediction model was established based on the data from a randomized clinical trial, which enrolled 196 patients with CSDH from February 2014 to November 2015. The following subjects were extracted: demographic characteristics, medical history, hematoma characters in imaging at admission, and clinical assessments. The outcome was self-absorption at the 8th week after admission. A least absolute shrinkage and selection operator (LASSO) regression model was implemented for data dimensionality reduction and feature selection. Multivariable logistic regression was adopted to establish the model, while the experimental results were presented by nomogram. Discrimination, calibration, and clinical usefulness were used to evaluate the performance of the nomogram. A total of 60 consecutive patients were involved in the external validation, which enrolled in a proof-of-concept clinical trial from July 2014 to December 2018.

Results: Diabetes mellitus history, hematoma volume at admission, presence of basal ganglia suppression, presence of septate hematoma, and usage of atorvastatin were the strongest predictors of self-absorption. The model had good discrimination [area under the curve (AUC), 0.713 (95% , 0.637-0.788)] and good calibration ( = 0.986). The nomogram in the validation cohort still had good discrimination [AUC, 0.709 (95% , 0.574-0.844)] and good calibration ( = 0.441). A decision curve analysis proved that the nomogram was clinically effective.

Conclusions: This prediction model can be used to obtain self-absorption probability in patients with CSDH, assisting in guiding the choice of therapy, whether they undergo non-surgical treatment or surgery.
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http://dx.doi.org/10.3389/fneur.2022.913495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355276PMC
July 2022

Clarifying winter clean heating importance: Insight chemical compositions and cytotoxicity exposure to primary and aged pollution emissions in China rural areas.

J Environ Manage 2022 Aug 4;320:115822. Epub 2022 Aug 4.

Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address:

Residential solid fuel combustion (RSFC) is an important source of PM. Here we investigate the cytotoxicity of primarily emitted and photochemically aged PM to A549 cells. Owing to the formation of water-soluble ions and organics (e.g., oPAHs and nPAHs), emission factors of PM were increased by 44.4% on average after 7-day equivalent photochemical aging, which greatly altered chemical profiles of freshly emitted PM. Consequently, the cytotoxicity varied with aging duration that 2-day and 7-day aged PM induced 22.5% and 35.1%, respectively, higher levels of reactive oxygen species than primary emissions. Similar increases were also observed for multi-cytotoxicity. Correlation analysis and western blot results collectively confirmed HO-1/Nrf-2 signaling pathway dominated the cytotoxicity of aged PM from RSFC, which was regulated by the enhanced o-PAHs and n-PAHs during photochemical aging. Thus, aged and secondary aerosol exposure needs to be paid more attention due to the enhanced cytotoxicity and the vast crowd involved.
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http://dx.doi.org/10.1016/j.jenvman.2022.115822DOI Listing
August 2022

MicroRNA alteration in cerebrospinal fluid from comatose patients with traumatic brain injury after right median nerve stimulation.

Exp Brain Res 2022 Aug 7. Epub 2022 Aug 7.

Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.
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http://dx.doi.org/10.1007/s00221-022-06414-7DOI Listing
August 2022

Association of Inhaled Corticosteroids With All-cause Death Risk in COPD Patients: A Meta-analysis of Sixty Randomized Controlled Trials.

Chest 2022 Jul 31. Epub 2022 Jul 31.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Inhaled corticosteroids (ICSs) have been widely used in the maintenance therapy of COPD. However, whether inhaled therapy containing ICSs can reduce the all-cause death risk and the possible benefited patient subgroups are unclear.

Research Question: Does inhaled therapy containing ICSs reduce the all-cause death risk in COPD patients compared with other inhaled therapy not containing ICSs?

Study Design And Methods: We searched PubMed, Cochrane Library, Embase, and Clinical Trials.gov for relevant randomized clinical trials (RCTs). Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% CIs.

Results: Sixty RCTs enrolling 103,034 patients were analyzed. Inhaled therapy containing ICSs (Peto OR, 0.90; 95% CI, 0.84-0.97), especially triple therapy (Peto OR, 0.73; 95% CI, 0.59-0.91), was associated with a reduction in the cause-death risk among COPD patients when compared to inhaled therapy without ICSs. Subgroup analyses revealed that treatment duration > 6 months (Peto OR, 0.90; 95% CI, 0.83-0.97), medium-dose (Peto OR, 0.71; 95% CI, 0.56-0.91)/low-dose ICSs (Peto OR, 0.88; 95% CI, 0.79-0.97), and budesonide (Peto OR, 0.75; 95% CI, 0.59-0.94) were involved in this association. The predictors of this association included eosinophil counts ≥ 200/μL or percentage ≥ 2%, documented history of moderate and severe exacerbations in the previous year ≥ 2, GOLD stage III or IV, age < 65 years old, and BMI ≥ 25, among which eosinophil counts ≥ 200/μL (Peto OR, 0.58; 95% CI, 0.36-0.95) was the strongest predictor.

Interpretation: Inhaled therapy containing ICSs, especially triple therapy, longer than 6 months, was associated with a reduction in the cause-death risk in COPD patients. The predictors of this association included medication factors and patient characteristics, among which eosinophil counts ≥ 200/μL was the strongest predictor.

Trial Registry: PROSPERO: CRD42022304725; https://www.crd.york.ac.uk/PROSPERO/.
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http://dx.doi.org/10.1016/j.chest.2022.07.015DOI Listing
July 2022

Gap junction intercellular communication mediates cadmium-induced apoptosis in hepatocytes via the Fas/FasL pathway.

Environ Toxicol 2022 Aug 3. Epub 2022 Aug 3.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China.

As a common environmental pollutant, cadmium (Cd) causes damage to many organs of the body. Gap junction intercellular communication (GJIC) represents one of the most important routes of rapid signaling between cells. However, the mechanisms underlying GJIC's role in hepatotoxicity induced by Cd remain unknown. We established a Cd poisoning model in vitro by co-culturing Cd-exposed and unexposed hepatocytes and found that 18β-glycyrrhetinic acid (GA), a GJIC inhibitor, can effectively reduce the apoptosis rate of healthy cells co-cultured with apoptotic cells treated with Cd. We also found that anti-FasL antibody had the same effect. However, in mono-cultured cells, GA treatment in combination with Cd was found to aggravate the damage induced by Cd exposure, increase the level of oxidative stress and protein expression of HO-1, decrease the mitochondrial membrane potential, incur more serious morphological damage to mitochondria than Cd treatment alone. Moreover, compared with Cd-only exposure, GA and Cd co-treatment further increased the expression levels of the apoptosis-related proteins Fas, FasL, FADD and the ratio of Bax/Bcl-2, inhibited the protein expression of ASK1 and Daxx. We also found that the protein expression of Daxx in siFADD + Cd hepatocytes was significantly higher than in Cd-treated cells. Thus, our study suggests that gap junction inhibition may play a dual role in Cd-induced cell damage by inhibiting the transmission of death signals from damaged cells to healthy cells but also aggravating the transmission of death signals between damaged cells, and that the Fas/FasL-mediated death receptor pathway may play an important role in this process.
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http://dx.doi.org/10.1002/tox.23629DOI Listing
August 2022

On-bead DNA synthesis triggered by allosteric probe for detection of carcinoembryonic antigen.

Mikrochim Acta 2022 08 1;189(8):305. Epub 2022 Aug 1.

Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education, Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.

Sensitive quantification of protein biomarkers is highly desired for clinical diagnosis and treatment. Yet, unlike DNA/RNA which can be greatly amplified by PCR/RT-PCR, the amplification and detection of trace amount of proteins remain a great challenge. Here, we combined allosteric probe (AP) with magnetic bead (MB) for assembling an on-bead DNA synthesis system (named as APMB) to amplify protein signals. The AP is designed and conjugated onto the MB, enabling the protein biomarker to be separated and enriched. Once recognizing the biomarker, the AP alters its conformation to initiate DNA synthesis on beads for primary signal amplification. During the DNA synthesis, biotin-dATPs are incorporated into the newly synthesized DNA strands. Then, the biotin-labeled DNA specifically captures streptavidin (STR)-conjugated horseradish peroxidase (HRP), which is used to catalyze a colorimetric reaction for secondary signal amplification. By using carcinoembryonic antigen (CEA) as a protein model, the APMB can quantify protein biomarkers of as low as 0.01 ng/mL. The response values measured by APMB are linearly related to the protein concentrations in the range 0.05 to 20 ng/mL. Clinical examination demonstrated good practicability of the APMB in quantifying serum protein biomarker. The on-bead DNA synthesis could be exploited to improve protein signal amplification, thus facilitating protein biomarker detection of low abundance for early diagnosis.
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http://dx.doi.org/10.1007/s00604-022-05404-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342938PMC
August 2022

Craniocervical Manual Lymphatic Drainage Increases the Efficiency of Atorvastatin-Based Treatment of Chronic Subdural Hematoma.

Transl Stroke Res 2022 Jul 30. Epub 2022 Jul 30.

Department of Neurosurgery, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, China.

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.
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http://dx.doi.org/10.1007/s12975-022-01062-zDOI Listing
July 2022

Pharmacodynamic Target Assessment and PK/PD Cutoff Determination for Gamithromycin Against in Piglets.

Front Vet Sci 2022 11;9:945632. Epub 2022 Jul 11.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Gamithromycin is a long-acting azalide antibiotic that has been developed recently for the treatment of swine respiratory diseases. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff, and optimum dosing regimen of gamithromycin were evaluated in piglets against in China, including a subset with capsular serotype 2. Short post-antibiotic effects (PAEs) (0.5-2.6 h) and PA-SMEs (2.4-7.7 h) were observed for gamithromycin against . The serum matrix dramatically facilitated the intracellular uptake of gamithromycin by strains, thus contributing to the potentiation effect of serum on their susceptibilities, with a Mueller-Hinton broth (MHB)/serum minimum inhibitory concentration (MIC) ratio of 28.86 for . Dose-response relationship demonstrated the area under the concentration (AUC)/MIC ratio to be the predictive PK/PD index closely linked to activity ( > 0.93). For infections, the net stasis, 1-log, and 2-log kill effects were achieved at serum AUC/MIC targets of 17.9, 49.1, and 166 h, respectively. At the current clinical dose of 6.0 mg/kg, gamithromycin PK/PD cutoff value was determined to be 8 mg/L. A PK/PD-based dose assessment demonstrated that the optimum dose regimen of gamithromycin to achieve effective treatments for the observed wild-type MIC distribution of in China with a probability of target attainment (PTA) ≥ 90% was 2.53 mg/kg in this study. These results will aid in the development of clinical dose-optimization studies and the establishment of clinical breakpoints for gamithromycin in the treatment of swine respiratory infections due to .
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http://dx.doi.org/10.3389/fvets.2022.945632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310021PMC
July 2022

Facile Fabrication of 1-Methylimidazole/Cu Nanozyme with Enhanced Laccase Activity for Fast Degradation and Sensitive Detection of Phenol Compounds.

Molecules 2022 Jul 23;27(15). Epub 2022 Jul 23.

Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.

Facile construction of functional nanomaterials with laccase-like activity is important in sustainable chemistry since laccase is featured as an efficient and promising catalyst especially for phenolic degradation but still has the challenges of high cost, low activity, poor stability and unsatisfied recyclability. In this paper, we report a simple method to synthesize nanozymes with enhanced laccase-like activity by the self-assembly of copper ions with various imidazole derivatives. In the case of 1-methylimidazole as the ligand, the as-synthesized nanozyme (denoted as Cu-MIM) has the highest yield and best activity among the nanozymes prepared. Compared to laccase, the of Cu-MIM nanozyme to phenol is much lower, and the is 6.8 times higher. In addition, Cu-MIM maintains excellent stability in a variety of harsh environments, such as high pH, high temperature, high salt concentration, organic solvents and long-term storage. Based on the Cu-MIM nanozyme, we established a method for quantitatively detecting phenol concentration through a smartphone, which is believed to have important applications in environmental protection, pollutant detection and other fields.
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http://dx.doi.org/10.3390/molecules27154712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331362PMC
July 2022

Multi-Substituted Quinolines as HIV-1 Integrase Allosteric Inhibitors.

Viruses 2022 07 2;14(7). Epub 2022 Jul 2.

Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA.

Allosteric HIV-1 integrase (IN) inhibitors, or ALLINIs, are a new class of antiviral agents that bind at the dimer interface of the IN, away from the enzymatic catalytic site and block viral replication by triggering an aberrant multimerization of the viral enzyme. To further our understanding of the important binding features of multi-substituted quinoline-based ALLINIs, we have examined the IN multimerization and antiviral properties of substitution patterns at the 6 or 8 position. We found that the binding properties of these ALLINIs are negatively impacted by the presence of bulky substitutions at these positions. In addition, we have observed that the addition of bromine at either the 6 (6-bromo) or 8 (8-bromo) position conferred better antiviral properties. Finally, we found a significant loss of potency with the 6-bromo when tested with the ALLINI-resistant IN A128T mutant virus, while the 8-bromo analog retained full effectiveness.
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http://dx.doi.org/10.3390/v14071466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324412PMC
July 2022

Overexpression of an Inositol Phosphorylceramide Glucuronosyltransferase Gene Inhibits Na Uptake in Sweet Potato Roots.

Genes (Basel) 2022 Jun 24;13(7). Epub 2022 Jun 24.

Institute of Integrative Plant Biology, School of Life Sciences, Jiangsu Normal University, Xuzhou 221116, China.

is a glycosyltransferase capable of synthesizing the glycosyl inositol phosphorylceramide (GIPC) sphingolipid. The GIPC sphingolipid is a Na receptor on cell membranes which can sense extracellular Na concentrations, promote the increase in intracellular Ca concentrations, and plays critical roles in maintaining intracellular Na balance. Therefore, the gene plays an important role in the genetic improvement of crop salt tolerance. Herein, the gene, which encodes an ortholog of , from sweet potato was cloned. -mediated in vivo transgenic technology, non-invasive micro-measuring technology (NMT) and Na fluorescence imaging technology were then combined to quickly study the potential function of in salt tolerance. The data showed that was involved in the regulation of root cell Na balance, and the overexpression of could not promote sweet potato root cell Na efflux under salt stress, but it could significantly inhibit the Na absorption of root cells, thereby reducing the accumulation of Na in root cells under salt stress. Additionally, Ca efflux in transgenic root cells was slightly higher than that in control roots under salt stress. Collectively, an efficient transgenic method for gene function studies was established, and our results suggested that acts as a candidate gene for the genetic enhancement of sweet potato salt tolerance.
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http://dx.doi.org/10.3390/genes13071140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317492PMC
June 2022

Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.

Biomolecules 2022 07 14;12(7). Epub 2022 Jul 14.

Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.

Src family kinases (SFKs) are non-receptor tyrosine kinases and play a key role in regulating signal transduction. The mechanism of SFKs in various tumors has been widely studied, and there are more and more studies on its role in the kidney. Acute kidney injury (AKI) is a disease with complex pathogenesis, including oxidative stress (OS), inflammation, endoplasmic reticulum (ER) stress, autophagy, and apoptosis. In addition, fibrosis has a significant impact on the progression of AKI to developing chronic kidney disease (CKD). The mortality rate of this disease is very high, and there is no effective treatment drug at present. In recent years, some studies have found that SFKs, especially Src, Fyn, and Lyn, are involved in the pathogenesis of AKI. In this paper, the structure, function, and role of SFKs in AKI are discussed. SFKs play a crucial role in the occurrence and development of AKI, making them promising molecular targets for the treatment of AKI.
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http://dx.doi.org/10.3390/biom12070984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312434PMC
July 2022

Isolated Posterior Instrumentation for Selected Cases of Thoracic and Lumbar Spinal Tuberculosis without Radical Debridement.

Z Orthop Unfall 2022 Jul 26. Epub 2022 Jul 26.

Department of Orthopedics Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: The purpose of this study was to evaluate the clinical outcomes of thoracic and lumbar spinal tuberculosis treated with isolated posterior instrumentation without radical debridement.

Methods: This study retrospectively analyzed 73 patients with thoracic and lumbar spinal tuberculosis who were treated using isolated posterior instrumentation without radical debridement in our hospital between January 2012 to December 2019. The patient group was composed of 42 men and 31 women with a mean age of 67.3 ± 8.6 years. The tuberculosis spine instability score (TSIS) was used to evaluate spine stability. All patients received chemotherapy for 18 months after surgery. The time of surgery, blood loss, visual analogue score (VAS), kyphosis angle, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), Frankel grading, SF-36 scores, and local recurrence and complications were analyzed to evaluate the efficacy of isolated posterior instrumentation surgery in the treatment of thoracic and lumbar spinal tuberculosis.

Results: All patients were followed up for 12 to 24 months (mean 14 ± 3.2 months). The mean surgical time was 1.2 ± 1.4 h (range, 1.2-1.6 h), and mean blood loss was 107 ± 18 mL. The postoperative symptoms were obviously relieved. The VAS, kyphosis angle, DI, and ESR decreased, respectively, from 8.24 ± 1.32, 19.82 ± 3.42, 46.25 ± 3.62, and 49.64 ± 17.61 to 1.12 ± 0.21, 7.14 ± 0.81, 20.17 ± 5.11, and 0.35 ± 1.13 at final follow-up. In comparison to preoperative values, SF-36 scores were significantly improved at final follow-up and the differences were statistically significant (p < 0.05). All patients achieved neurological recovery at the final follow-up. There were no recurrences or complications in any of the patients.

Conclusion: Isolated posterior instrumentation without radical debridement is a suitable minor surgical trauma that offers a remarkable advantage of effective pain relief, improvement in neurological function and performance status, and no local recurrence for selected patients with thoracic and lumbar spinal tuberculosis.
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http://dx.doi.org/10.1055/a-1851-5509DOI Listing
July 2022

Phylogenomic analysis of Salmonella Indiana ST17, an emerging MDR clonal group in China.

J Antimicrob Chemother 2022 Jul 26. Epub 2022 Jul 26.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, Guangdong, P. R.  China.

Objectives: To reconstruct the genomic epidemiology and evolution of MDR Salmonella Indiana in China.

Methods: A total of 108 Salmonella Indiana strains were collected from humans and livestock in China. All isolates were subjected to WGS and antimicrobial susceptibility testing. Phylogenetic relationships and evolutionary analyses were conducted using WGS data from this study and the NCBI database.

Results: Almost all 108 Salmonella Indiana strains displayed the MDR phenotype. Importantly, 84 isolates possessed concurrent resistance to ciprofloxacin and cefotaxime. WGS analysis revealed that class 1 integrons on the chromosome and IncHI2 plasmids were the key vectors responsible for multiple antibiotic resistance gene (ARG) [including ESBL and plasmid-mediated quinolone resistance (PMQR) genes] transmission among Salmonella Indiana. The 108 Salmonella Indiana dataset displayed a relatively large core genome and ST17 was the predominant ST. Moreover, the global ST17 Salmonella Indiana strains could be divided into five distinct lineages, each of which was significantly associated with a geographical distribution. Genomic analysis revealed multiple antimicrobial resistance determinants and QRDR mutations in Chinese lineages, which almost did not occur in other global lineages. Using molecular clock analysis, we hypothesized that ST17 isolates have existed since 1956 and underwent a major population expansion from the 1980s to the 2000s and the genetic diversity started to decrease around 2011, probably due to geographical barriers, antimicrobial selective pressure and MDR, favouring the establishment of this prevalent multiple antibiotic-resistant lineage and local epidemics.

Conclusions: This study revealed that adaptation to antimicrobial pressure was possibly pivotal in the recent evolutionary trajectory for the clonal spread of ST17 Salmonella Indiana in China.
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http://dx.doi.org/10.1093/jac/dkac243DOI Listing
July 2022

Detecting Retinal Neural and Stromal Cell Classes and Ganglion Cell Subtypes Based on Transcriptome Data with Deep Transfer Learning.

Bioinformatics 2022 Jul 25. Epub 2022 Jul 25.

Department of Ophthalmology, University of Tennessee Health Science Center, TN, USA.

Motivation: To develop and assess the accuracy of deep learning models that identify different retinal cell types, as well as different retinal ganglion cell (RGC) subtypes, based on patterns of single-cell RNA sequencing (scRNA-seq) in multiple data sets.

Results: Deep domain adaptation models were developed and tested using three different datasets. The first dataset included 44,808 single retinal cells from mice (39 cell types) with 24,658 genes, the second dataset included 6,225 single RGCs from mice (41 subtypes) with 13,616 genes, and the third dataset included 35,699 single RGCs from mice (45 subtypes) with 18,222 genes. We used four loss functions in the learning process to align the source and target distributions, reduce misclassification errors, and maximize robustness. Models were evaluated based on classification accuracy and confusion matrix. The accuracy of the model for correctly classifying 39 different retinal cell types in the first dataset was ∼92%. Accuracy in the second and third datasets reached ∼97% and 97% in correctly classifying 40 and 45 different RGCs subtypes, respectively. Across a range of seven different batches in the first dataset, the accuracy of the lead model ranged from 74% to nearly 100%. The lead model provided high accuracy in identifying retinal cell types and RGC subtypes based on scRNA-seq data. The performance was reasonable based on data from different batches as well. The validated model could be readily applied to scRNA-seq data to identify different retinal cell types and subtypes.

Availability: The code and datasets are available on https://github.com/DM2LL/Detecting-Retinal-Cell-Classes-and-Ganglion-Cell-Subtypes. We have also added the class labels of all samples to the datasets.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btac514DOI Listing
July 2022

Genome-Wide Analysis of Ascorbic Acid Metabolism Related Genes in × and Its Expression Pattern Analysis in Strawberry Fruits.

Front Plant Sci 2022 6;13:954505. Epub 2022 Jul 6.

Institute of Forestry and Pomology, Beijing Academy of Forestry and Pomology Sciences, Beijing, China.

Ascorbic acid (AsA) is an important antioxidant for scavenging reactive oxygen species and it is essential for human health. Strawberry ( × ) fruits are rich in AsA. In recent years, strawberry has been regarded as a model for non-climacteric fruit ripening. However, in contrast to climacteric fruits, such as tomato, the regulatory mechanism of AsA accumulation in strawberry fruits remains largely unknown. In this study, we first identified 125 AsA metabolism-related genes from the cultivated strawberry "Camarosa" genome. The expression pattern analysis using an available RNA-seq data showed that the AsA biosynthetic-related genes in the D-mannose/L-galactose pathway were downregulated remarkably during fruit ripening which was opposite to the increasing AsA content in fruits. The D-galacturonate reductase gene () in the D-Galacturonic acid pathway was extremely upregulated in strawberry receptacles during fruit ripening. The gene above belongs to the aldo-keto reductases (AKR) superfamily and has been proposed to participate in AsA biosynthesis in strawberry fruits. To explore whether there are other genes in the AKR superfamily involved in regulating AsA accumulation during strawberry fruit ripening, we further implemented a genome-wide analysis of the AKR superfamily using the octoploid strawberry genome. A total of 80 genes were identified from the genome and divided into 20 subgroups based on phylogenetic analysis. These genes were unevenly distributed on 23 chromosomes. Among them, nine genes showed increased expression in receptacles as the fruit ripened, and notably, was the most dramatically upregulated gene in receptacles. Compared with fruits at green stage, its expression level increased by 142-fold at red stage. The qRT-PCR results supported that the expression of was increased significantly during fruit ripening. In particular, the was the only gene that was significantly upregulated by abscisic acid (ABA) and suppressed by nordihydroguaiaretic acid (NDGA, an ABA biosynthesis blocker), indicating might play important roles in ABA-mediated strawberry fruit ripening. In a word, our study provides useful information on the AsA metabolism during strawberry fruit ripening and will help understand the mechanism of AsA accumulation in strawberry fruits.
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http://dx.doi.org/10.3389/fpls.2022.954505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296770PMC
July 2022

Transforming growth factor-β induced protein regulates pulmonary fibrosis via the G-protein signaling modulator 2 /Snail axis.

Peptides 2022 09 22;155:170842. Epub 2022 Jul 22.

Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, No. 278, Baoguang Avenue, Xindu District, Chengdu, Sichuan 610500, China; Chengdu Medical College, No. 783, Xindu Avenue, Xindu District, Chengdu, Sichuan 610500, China. Electronic address:

Pulmonary fibrosis, a severe condition that can progress to respiratory failure and death, is characterized by aberrant activation/proliferation of fibroblasts and excessive extracellular matrix (ECM) deposition and has limited therapeutic options. Identifying novel mediators of pulmonary fibrosis is currently needed to facilitate the development of more effective therapeutic strategies targeting pulmonary fibrosis. The present study was designed to investigate whether transforming growth factor-β (TGF-β) induced protein (TGFBI), an extracellular matrix protein, regulates pulmonary fibrosis in vitro and in vivo and the possible mechanism of actions. It was found that protein expressions of TGFBI were significantly upregulated and G-protein signaling modulator 2 (GPSM2) expression downregulated in fibrotic lung tissues from bleomycin (BLM)-induced rats and TGF-β1-stimulated human lung IMR-90 fibroblasts. Either silencing TGFBI with specific siRNA or treatment with the TGF-β signaling inhibitor SB431542 significantly inhibited TGF-β1-induced fibrotic effects and dysregulation of GPSM2 and Snail expressions in IMR-90 fibroblasts. Moreover, GPSM2 overexpression also inhibited TGF-β1-induced fibrotic effects and Snail upregulation in IMR-90 fibroblasts. Silencing Snail with specific siRNA attenuated TGF-β1-induced fibrotic effects. Therefore, our findings suggest that the extracellular matrix protein TGFBI mediates pulmonary fibrosis through regulation of the GPSM2/Snail axis, which identifies TGFBI as a novel mediator of pulmonary fibrosis and may be a potential therapeutic target for the treatment of pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.peptides.2022.170842DOI Listing
September 2022

The changing epidemiology of liver diseases in Asia.

Liver Int 2022 08;42(9):1926-1929

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

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http://dx.doi.org/10.1111/liv.15354DOI Listing
August 2022

Tumor Location May Independently Predict Survival in Patients With M0 Squamous Cell Carcinoma of the Penis.

Front Oncol 2022 5;12:927088. Epub 2022 Jul 5.

Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Background: To determine the association between tumor location and both clinicopathological characteristics and the survival of patients with M0 squamous cell carcinoma of the penis (SCCP).

Methods: Data of 455 patients diagnosed with M0 SCCP between 1975 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the United States National Cancer Institute. The effects of tumor location on overall survival (OS) and penile carcinoma-specific survival (PCSS) were analyzed using the Kaplan-Meier method. The Cox proportional hazards regression model was used to determine the impact of tumor location on PCSS.

Results: SCCP was more likely to occur in the prepuce or glans (90%). Although no significant difference was observed between the OS of patients with M0 SCCP in the prepuce or glans and those with M0 SCCP in the body of the penis (p = 0.307), the former had better PCSS (p = 0.024). Moreover, M0 SCCP in the prepuce or glans was also significantly associated with better PCSS in patients with advanced age (age ≥ 60 years, p = 0.011), other ethnicities (p = 0.003), T2-T4 stage (p = 0.036), larger tumors (≥3 cm, p = 0.001), no regional lymph nodes removed (p = 0.044), and radical surgery (p = 0.027). Multivariate analysis confirmed that tumor location is an independent prognostic factor for patients with M0 SCCP [hazard ratio (HR) 1.881, p = 0.026].

Conclusions: Tumor location is an independent prognostic factor for patients with M0 SCCP, and tumors in the prepuce or glans portend better PCSS.
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http://dx.doi.org/10.3389/fonc.2022.927088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294313PMC
July 2022

AMPK-PPARγ-Cidec Axis Drives the Fasting-Induced Lipid Droplet Aggregation in the Liver of Obese Mice.

Front Nutr 2022 4;9:917801. Epub 2022 Jul 4.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Intermittent fasting is one of the most common clinical treatments for the obesity, a main risk factor of the metabolic syndrome which can lead to a variety of diseases. Fasting-induced fat mobilization alters the metabolic state of lipid in the liver, predisposing to increase the hepatic lipid droplet aggregation and triglyceride levels. However, the underlying mechanisms regarding the lipid droplet aggregation in the liver after fasting remains elusive. Here, we report that a lipid droplet surface binding protein Cidec (cell death inducing DFFA like effector C) is activated by AMPK to regulate the hepatic lipid droplet fusion following fasting in obese mice. Specifically, we found that lipid droplets were significantly aggregated in the liver of high-fat-diet and mice after 16 and 24 h of fasting, accompanied by the dramatically up-regulated expression of . Consistently, overexpression of in the AML12 cells resulted in the intracellular lipid droplet aggregation. Furthermore, we showed that fasting caused the up-regulated expression of AMPK, which in turn activated the transcription of through the transcription factor PPARγ. Altogether, our observations reveal that fasting-induced hepatic lipid droplet aggregation is mediated by the AMPK-activated expression of via PPARγ, extending our understanding about the molecular mechanism of the impact of fasting on the obesity and providing potential targets for the treatment of human obesity.
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http://dx.doi.org/10.3389/fnut.2022.917801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289538PMC
July 2022

Molecular Epidemiology of New Delhi Metallo--Lactamase-Producing in Food-Producing Animals in China.

Front Microbiol 2022 1;13:912260. Epub 2022 Jul 1.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.

We conducted a molecular surveillance study for carbapenem-resistant (CRE) colonization in food-producing animals in China that included primarily swine and poultry for three consecutive years. A total of 2,771 samples from food-producing animals and their surrounding environments were collected from different regions in China from 2015 to 2017. Enrichment cultures supplemented with meropenem were used to isolate carbapenem non-susceptible isolates and these were subsequently identified by MALDI-TOF MS. Resistance phenotypes and genotypes were confirmed using antimicrobial susceptibility testing and molecular biological techniques. Genomic characteristics of the carbapenemase-producing isolates were investigated using whole genome sequencing (WGS) and bioinformatic analysis. In total, 88 NDM-positive were identified from 2,771 samples and 96.6% were . The New Delhi metallo--lactamase (NDM)-positive displayed a diversity of sequence types (ST), and ST48 and ST165 were the most prevalent. Three variants of ( , , and ) were detected and WGS indicated that predominated and was carried primarily on IncX3 plasmids. All these isolates were also multiply-drug resistant. These results revealed that food-producing animals in China are an important reservoir for NDM-positive and pose a potential threat to public health.
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http://dx.doi.org/10.3389/fmicb.2022.912260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284025PMC
July 2022

A cell membrane repair protein-based nanoformulation with multiple actuators for scarless wound healing.

J Mater Chem B 2022 Aug 4;10(30):5733-5742. Epub 2022 Aug 4.

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.

Diabetic wounds remain a major contributor to disability worldwide due to their difficulty of healing, and their primary etiologic factor involves impaired cell membrane repair. Additionally, ideal wound repair should prevent excessive scar formation from affecting tissue function following reconstruction. Therefore, the development of a therapeutic strategy for promoting rapid wound healing and reduced scar formation is urgently needed. In this study, a remote light-controlled thermosensitive nanoformulation was developed, which integrated the photothermal conversion performance of a photosensitizer and cell membrane repair protein (rhMG53). The nanoformulation not only protected rhMG53 from being degraded by proteases at the lesion site but also efficiently released this protein through photothermal stimulation. The nanoformulation remained stable at physiological temperatures and released approximately 80% rhMG53 at 45 °C. More protein was effectively delivered to tissue cells, achieving synergistic therapy with photothermal and rhMG53. By utilizing this approach, increased wound closure rate, reduced extent of cell membrane damage and inflammation, and improved cell function were observed in diabetic wounds. More importantly, [email protected] treatment inhibited excessive skin fibrosis and angiogenesis, indicating a reduction in scar formation. Collectively, this work reveals a promising strategy for high-quality wound repair and provides a new route for rapid scarless wound healing.
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http://dx.doi.org/10.1039/d2tb00992gDOI Listing
August 2022
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