Publications by authors named "Xin Tong"

554 Publications

Size-dependent biological effect of copper oxide nanoparticles exposure on cucumber (Cucumis sativus).

Environ Sci Pollut Res Int 2022 May 14. Epub 2022 May 14.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China.

Copper oxide nanoparticles (CuO NPs) have received considerable attention for their toxic effects on crops and potential application in agriculture. In order to investigate the biological effects of CuO NPs on plants, we exposed cucumber (Cucumis sativus) to two sizes of CuO NPs (510 nm, μCuO and 43 nm, nCuO). Results indicated that with concentration increased, the available Cu content in soil increased significantly. The addition of CuO NPs increased Cu content and other nutrient element (e.g., K, P, Mn, and Zn) content in plants. However, diverse particle sizes had different effects. The nCuO treatment had larger translocation factor, higher nutrient element content in fruits, and lower oxidative damage than μCuO treatment. Moreover, nCuO of 100 mg/kg could stimulate cucumber growth, while μCuO had no obvious effects on growth. Conclusively, CuO NPs could be used as copper fertilizer to supply copper to cucumber. The nCuO had better effects on improving the bioavailability of Cu and nutritional value of fruits. These results can help develop strategies for safe disposal of CuO NPs as agricultural fertilizer.
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http://dx.doi.org/10.1007/s11356-022-20662-8DOI Listing
May 2022

MAPKs trigger antiviral immunity by directly phosphorylating a rhabdovirus nucleoprotein in plants and insect vectors.

Plant Cell 2022 May 14. Epub 2022 May 14.

State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Signaling by the evolutionarily conserved mitogen-activated protein kinase or extracellular signal-regulated kinase (MAPK/ERK) plays critical roles in converting extracellular stimuli into immune responses. However, whether MAPK/ERK signaling induces virus immunity by directly phosphorylating viral effectors remains largely unknown. Barley yellow striate mosaic virus (BYSMV) is an economically important plant cytorhabdovirus that is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a propagative manner. Here, we found that the barley (Hordeum vulgare) MAPK MPK3 (HvMPK3) and the planthopper ERK (LsERK) proteins interact with the BYSMV nucleoprotein (N) and directly phosphorylate N protein primarily on serine 290. Overexpression of HvMPK3 inhibited BYSMV infection, whereas barley plants treated with the MAPK pathway inhibitor U0126 displayed greater susceptibility to BYSMV. Moreover, knockdown of LsERK promoted virus infection in SBPHs. A phosphomimetic mutant of the N Ser290 (S290D) completely abolished virus infection because of impaired self-interaction of BYSMV N and formation of unstable N-RNA complexes. Altogether, our results demonstrate that the conserved MAPK and ERK directly phosphorylate the viral nucleoprotein to trigger immunity against cross-kingdom infection of BYSMV in host plants and its insect vectors.
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http://dx.doi.org/10.1093/plcell/koac143DOI Listing
May 2022

Gamma-glutamyl Transpeptidase to Platelet Ratio Predicts Liver Injury in Hepatitis B e Antigen-negative Chronic Hepatitis B Patients With Normal Alanine Aminotransferase.

J Clin Transl Hepatol 2022 Apr 14;10(2):247-253. Epub 2021 Jul 14.

Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

Background And Aims: Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in these patients.

Methods: A total of 184 treatment-naïve HBeAg-negative CHB patients with detectable HBV DNA and normal ALT were enrolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis.

Results: The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of patients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the receiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis.

Conclusions: Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.
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http://dx.doi.org/10.14218/JCTH.2021.00151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039718PMC
April 2022

Ultrasensitive barocaloric material for room-temperature solid-state refrigeration.

Nat Commun 2022 Apr 28;13(1):2293. Epub 2022 Apr 28.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang, 110016, China.

One of the greatest obstacles to the real application of solid-state refrigeration is the huge driving fields. Here, we report a giant barocaloric effect in inorganic NHI with reversible entropy changes of [Formula: see text] ∼71 J K kg around room temperature, associated with a structural phase transition. The phase transition temperature, T, varies dramatically with pressure at a rate of dT/dP ∼0.79 K MPa, which leads to a very small saturation driving pressure of ΔP ∼40 MPa, an extremely large barocaloric strength of [Formula: see text] ∼1.78 J K kg MPa, as well as a broad temperature span of ∼41 K under 80 MPa. Comprehensive characterizations of the crystal structures and atomic dynamics by neutron scattering reveal that a strong reorientation-vibration coupling is responsible for the large pressure sensitivity of T. This work is expected to advance the practical application of barocaloric refrigeration.
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http://dx.doi.org/10.1038/s41467-022-29997-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051211PMC
April 2022

Two different aging paths in human blood revealed by integrated analysis of gene Expression, mutation and alternative splicing.

Gene 2022 Jun 19;829:146501. Epub 2022 Apr 19.

State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China. Electronic address:

Aging is a complex life process that human organs and tissues steadily and continuously decline. Aging has huge heterogeneity, which shows different aging rates among different individuals and in different tissues of the same individual. Many studies of aging are often contradictory and show little common signature. The integrated analysis of these transcriptome datasets will provide an unbiased global view of the aging process. Here, we integrated 8 transcriptome datasets including 757 samples from healthy human blood to study aging from three aspects of gene expression, mutations, and alternative splicing. Surprisingly, we found that transcriptome changes in blood are relatively independent of the chronological age. Further pseudotime analysis revealed two different aging paths (AgingPath1 and AgingPath2) in human blood. The differentially expressed genes (DEGs) along the two paths showed a limited overlap and are enriched in different biological processes. The mutations of DEGs in AgingPath1 are significantly increased in the aging process, while the opposite trend was observed in AgingPath2. Expression quantitative trait loci (eQTL) and splicing quantitative trait loci (sQTL) analysis identified 304 important mutations that can affect both gene expression and alternative splicing during aging. Finally, by comparison between aging and Alzheimer's disease, we identified 37 common DEGs in AgingPath1, AgingPath2 and Alzheimer's disease. These genes may contribute to the shift from aging state to Alzheimer's disease. In summary, this study revealed the two aging paths and the related genes and mutations, which provides a new insight into aging and aging-related disease.
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http://dx.doi.org/10.1016/j.gene.2022.146501DOI Listing
June 2022

Dural puncture epidural versus conventional epidural analgesia for labor: a systematic review and meta-analysis of randomized controlled studies.

J Anesth 2022 Apr 21. Epub 2022 Apr 21.

Department of Anesthesiology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, 20#, 3rd Segment, Ren Min Nan Lu, Chengdu, 610041, People's Republic of China.

Dural puncture epidural (DPE) technique is a modification of the conventional epidural (EP) technique in that the dura is intentionally punctured with a spinal needle but without any spinal injection. This meta-analysis aimed to evaluate the benefits and risks associated with the DPE technique for labor analgesia. Randomized trials comparing DPE analgesia with EP analgesia for labor pain relief were systematically searched in the database of Medline, Embase, Cochrane Controlled Trials Register, Web of Science, and China Biology Medicine till 1 August 2021. The primary outcome was the percentage of patients with satisfactory pain relief following DPE or EP analgesia, which was defined as visual analog scale (VAS) pain scores ≤ 3/10 (or 30/100) measured 10 min and 20 min after initiation of labor analgesia. Totally ten trials with 1099 patients were included in this review. DPE technique increased the percentage of patients with VAS pain score ≤ 3/10 (or 30/100) both at 10 min (RR 1.43; 95% CI 1.17, 1.74; p < 0.001; I = 0%) and 20 min (RR 1.13; 95% CI 1.04, 1.22; p = 0.005; I = 0%) after labor analgesia. No adverse event was found with DPE analgesia. We conclude that compared with EP analgesia, DPE analgesia is beneficial for labor pain relief by shortening the time to achieve satisfactory pain control. Meanwhile, DPE analgesia is not associated with increased adverse maternal/fetal events.
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http://dx.doi.org/10.1007/s00540-022-03061-8DOI Listing
April 2022

Neuropathologic damage induced by radiofrequency ablation at different temperatures.

Clinics (Sao Paulo) 2022 15;77:100033. Epub 2022 Apr 15.

Department of Thyroid Breast, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China. Electronic address:

Objective: To explore the molecular mechanism of neuropathologic damage induced by radiofrequency ablation at different temperatures.

Methods: This is basic research, and 36 SD rats were used to construct the neuropathological injury model. The rats were subjected to radiofrequency stimulation at different temperatures and were divided into 6 groups according to the temperature injury: 42°, 47°, 52°, 57°, 62°, and 67°C groups. Conduction time, conduction distance, and nerve conduction velocity were recorded after temperature injury. HE-staining was used to observe the histopathological morphology of the sciatic nerve. The expression of SCN9A, SCN3B, and NFASC protein in sciatic nerve tissue were detected by western blot.

Results: With the increase in temperature, nerve conduction velocity gradually decreased, and neurons were damaged when the temperature was 67°C. HE-staining showed that the degrees of degeneration of neurons in rats at 47°, 52°, 57°, 62°, and 67°C were gradually increased. The expression of SCN9A, SCN3B protein in 57°, 62°, 67°C groups were much higher than that of NC, 42°, 47°, 52°C groups. However, the expression of NFASC protein in 57°, 62°, 67°C groups was much lower than that of the NC, 42°, 47°, 52°C groups.

Conclusion: There was a positive correlation between temperature caused by the radiofrequency stimulation to neuropathological damage. The mechanism is closely related to the expression of SCN9A, SCN3B, and NFASC protein in nerve tissue caused by heat transfer injury.
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http://dx.doi.org/10.1016/j.clinsp.2022.100033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035646PMC
April 2022

Novel urea derivative-loaded PLGA nanoparticles to inhibit caries-associated .

RSC Adv 2022 Jan 2;12(7):4072-4080. Epub 2022 Feb 2.

Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University Nanjing Jiangsu 210008 China

Caries is the most common chronic infectious disease in the human oral cavity and the existing anti-caries agents may lead to drug resistance and microecological imbalance. A novel urea derivative, 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea, has a potentially prominent antibacterial effect on cariogenic bacterial strain UA159. In this study, we encapsulated the water-insoluble urea derivative in poly(lactic--glycolic acid) (PLGA) nanoparticles, performed physicochemical characterizations and explored its potential as a caries-preventive agent. The results showed that the drug-loaded PLGA nanoparticles exhibited satisfying surface morphology, particle size, size distribution and stability. With an optimized theoretical drug loading (10%), the drug-loaded PLGA nanoparticles exhibited negligible cytotoxicity against human oral squamous cell carcinoma cells. We noticed a biphasic drug release and the rate and cumulative release was higher in an acidic environment (pH 4.5) compared to a neutral environment (pH 7.4). The drug-loaded PLGA nanoparticles significantly inhibited the growth and lactic acid production of planktonic as well as biofilms. Our results indicate that the novel urea derivative-loaded PLGA nanoparticles serve as a promising anti-caries agent with remarkable pharmaceutical characteristics, low cytotoxicity, and satisfying antimicrobial effect.
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http://dx.doi.org/10.1039/d1ra09314bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981093PMC
January 2022

Dexmedetomidine reduces postoperative pain and speeds recovery after bariatric surgery: a meta-analysis of randomized controlled trials.

Surg Obes Relat Dis 2022 Mar 9. Epub 2022 Mar 9.

Department of Anesthesiology, The Third People's Hospital of Chengdu, Chengdu, China. Electronic address:

Background: Dexmedetomidine in opioid-sparing analgesia promotes enhanced recovery and improves postoperative outcomes.

Objectives: This study aimed to explore the safety and efficacy of dexmedetomidine in bariatric surgery.

Setting: Meta-analysis.

Methods: We selected studies from Pubmed, Embase, Web of Science, and the Cochrane Central Registry of Controlled Trials before 20 April, 2021. The primary outcomes were pain scores and intravenous morphine equivalents (IVME) in the post anesthesia care unit (PACU) and postoperative day 1 (POD1). The secondary outcomes included postoperative nausea and vomiting (PONV), the length of hospital stay (LOS), intraoperative mean arterial pressure (MAP) and heart rate (HR).

Results: We extracted 697 participants from 10 randomized controlled trials. Dexmedetomidine reduced PACU pain scores (MD = -1.51, 95% confidence interval [CI]: -2.60 to -.42) after bariatric surgery, especially laparoscopic Roux-en-Y gastric bypass (MD = -3.05, 95%CI: -3.77 to -2.33), but it did not affect POD1 pain scores (MD = .20, 95%CI: -.85 to 1.26). Dexmedetomidine can reduce PACU IVME (MD = -4.29, 95%CI: -6.59 to -1.99), but does not reduce POD1 IVME (MD = -.36, 95%CI: -2.41 to 1.68). In addition, dexmedetomidine significantly reduced PONV both in PACU (OR = .28, 95%CI: .14-.54) and POD1 (OR = .24, 95%CI: .14-.4), shortened LOS (MD = -.29, 95%CI: -.49 to -.10), and had little effect on intraoperative MAP (MD = -6.64, 95%CI: -9.52 to -3.76) and HR (MD = -4.8, 95%CI: -11.55 to 1.94).

Conclusion: In conclusion, the use of dexmedetomidine in opioid-sparing analgesia contributes to postoperative analgesia after bariatric surgery, but the heterogeneity was high. In addition, dexmedetomidine is beneficial for enhanced recovery.
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http://dx.doi.org/10.1016/j.soard.2022.03.002DOI Listing
March 2022

Capillary-Assisted Fabrication of Thin-Film Nanocomposite Membranes for Improved Solute-Solute Separation.

Environ Sci Technol 2022 May 14;56(9):5849-5859. Epub 2022 Apr 14.

School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.

Efficient separation of harmful contaminants (e.g., per- and polyfluoroalkyl substances, PFASs) from valuable components (water and nutrients) is essential to the resource recovery from domestic wastewater for agricultural purposes. Such selective recovery requires precise separation at the angstrom scale. Although nanofiltration (NF) has the potential to achieve solute-solute separation, the state-of-the-art polyamide (PA) membranes are typically constrained by limited precision of solute-solute selectivity and their well-documented permeability-selectivity trade-off. Herein, we present a novel capillary-assisted interfacial polymerization (CAIP) approach to generate metal-organic framework (MOF)-PA nanocomposite membranes with reduced surface charges and more uniform pore sizes that favor solute selectivity by enhanced size exclusion. By uniquely regulating the PA-MOF interactions using the capillary force, CAIP results in effective exposure of MOF nanochannels on the membrane surface and a PA matrix with a high cross-linking gradient in the vertical direction, both of which contribute to an exceptional water permeance of ∼18.7 LMH/bar and an unprecedentedly high selectivity between nutrient ions and PFASs. Our CAIP approach breaks new ground for utilizing nanoparticles with nanochannels in fabricating the next-generation, fit-for-purpose NF membranes for improved solute-solute separations.
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http://dx.doi.org/10.1021/acs.est.2c01728DOI Listing
May 2022

Phosphorus-Doped Graphene Electrocatalysts for Oxygen Reduction Reaction.

Nanomaterials (Basel) 2022 Mar 29;12(7). Epub 2022 Mar 29.

Centre Énergie, Matériaux et Télécommunications, Institut National de la Recherche Scientifique (INRS), 1650 Boulevard Lionel-Boulet, Varennes, QC J3X 1P7, Canada.

Developing cheap and earth-abundant electrocatalysts with high activity and stability for oxygen reduction reactions (ORRs) is highly desired for the commercial implementation of fuel cells and metal-air batteries. Tremendous efforts have been made on doped-graphene catalysts. However, the progress of phosphorus-doped graphene (P-graphene) for ORRs has rarely been summarized until now. This review focuses on the recent development of P-graphene-based materials, including the various synthesis methods, ORR performance, and ORR mechanism. The applications of single phosphorus atom-doped graphene, phosphorus, nitrogen-codoped graphene (P, N-graphene), as well as phosphorus, multi-atoms codoped graphene (P, X-graphene) as catalysts, supporting materials, and coating materials for ORR are discussed thoroughly. Additionally, the current issues and perspectives for the development of P-graphene materials are proposed.
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http://dx.doi.org/10.3390/nano12071141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000525PMC
March 2022

Morphological characteristics associated with ruptured intracranial vertebral artery dissecting aneurysms.

J Neurointerv Surg 2022 Apr 6. Epub 2022 Apr 6.

Department of Neurosurgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China

Objective: Morphological risk factors for the rupture of intracranial vertebral artery dissecting aneurysms (IVADAs) have not been well characterized. In this study, we aim to identify morphological characteristics associated with IVADA rupture.

Methods: We conducted a retrospective study of 249 consecutive patients with single IVADAs (31 ruptured and 218 unruptured) admitted to Beijing Tiantan Hospital between January 2016 and December 2020. Various morphological parameters were measured using three-dimensional digital subtraction angiography images. Univariate and multivariate logistic regression analyses were performed to identify morphological characteristics associated with IVADA rupture.

Results: Univariate regression analysis revealed that the coexistence of significant proximal and distal stenosis and posterior inferior cerebellar artery (PICA) involvement were associated with IVADA rupture, while the origin from the dominant vertebral artery was inversely associated with the rupture. Multivariate regression analysis demonstrated that the coexistence of significant proximal and distal stenosis (OR 22.00, 95% CI 5.60 to 86.70, p<0.001) and PICA involvement (OR 4.55, 95% CI 1.36 to 15.20, p=0.014) were independently associated with IVADA rupture.

Conclusion: The coexistence of significant proximal and distal stenosis and PICA involvement were independently associated with IVADA rupture. These morphological characteristics may facilitate the assessment of rupture risk in patients with IVADAs.
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http://dx.doi.org/10.1136/neurintsurg-2022-018744DOI Listing
April 2022

Cost-effective analysis of mechanical thrombectomy alone in the treatment of acute ischaemic stroke: a Markov modelling study.

BMJ Open 2022 Apr 6;12(4):e059098. Epub 2022 Apr 6.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

Objective: Recently, a randomised controlled trial (DIRECT-MT) demonstrated that mechanical thrombectomy (MT) was non-inferior to MT with intravenous alteplase as to the functional outcomes. This study aims to investigate whether MT alone is cost-effective compared with MT with alteplase in China.

Methods: A Markov decision analytic model was built from the Chinese healthcare perspective using a lifetime horizon. Probabilities, costs and outcomes data were obtained from the DIRECT-MT trial and other most recent/comprehensive literature. Base case calculation was conducted to compare the costs and effectiveness between MT alone and MT with alteplase. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the results.

Results: MT alone had a lower cost and higher effectiveness compared with MT with alteplase. The probabilistic sensitivity analysis demonstrated that, over a lifetime horizon, MT alone had a 99.5% probability of being cost-effective under the willingness-to-pay threshold of 1× gross domestic product per capita in China based on data obtained from the DIRECT-MT trial. These results remained robust under one-way sensitivity analysis.

Conclusions: MT alone was cost-effective compared with MT with alteplase in China. However, cautions are needed to extend this conclusion to regions outside of China.
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http://dx.doi.org/10.1136/bmjopen-2021-059098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987747PMC
April 2022

Economic Evaluation of Ticagrelor Plus Aspirin Versus Aspirin Alone for Acute Ischemic Stroke and Transient Ischemic Attack.

Front Pharmacol 2022 18;13:790048. Epub 2022 Mar 18.

Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Although ticagrelor plus aspirin is more effective than aspirin alone in preventing the 30-day risk of a composite of stroke or death in patients with an acute mild-to-moderate ischemic stroke (IS) or transient ischemic attack (TIA), the cost-effectiveness of this combination therapy remains unknown. This study aims to determine the cost-effectiveness of ticagrelor plus aspirin compared with aspirin alone. A combination of decision tree and Markov model was built to estimate the expected costs and quality-adjusted life-years (QALYs) associated with ticagrelor plus aspirin and aspirin alone in the treatment of patients with an acute mild-to-moderate IS or TIA. Model inputs were extracted from published sources. One-way sensitivity, probabilistic sensitivity, and subgroup analyses were performed to test the robustness of the findings. Compared with aspirin alone, ticagrelor plus aspirin gained an additional lifetime QALY of 0.018 at an additional cost of the Chinese Yuan Renminbi (¥) of 269, yielding an incremental cost-effectiveness ratio of ¥15,006 (US$2,207)/QALY. Probabilistic sensitivity analysis showed that ticagrelor plus aspirin had a probability of 99.99% being highly cost-effective versus aspirin alone at the current willingness-to-pay threshold of ¥72,447 (US$10,500)/QALY in China. These findings remain robust under one-way sensitivity and subgroup analyses. The results indicated that early treatment with a 30-days ticagrelor plus aspirin for an acute mild-to-moderate IS or TIA is highly cost-effective in a Chinese setting.
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http://dx.doi.org/10.3389/fphar.2022.790048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971565PMC
March 2022

RNA demethylase ALKBH5 inhibits TGF-β-induced EMT by regulating TGF-β/SMAD signaling in non-small cell lung cancer.

FASEB J 2022 05;36(5):e22283

Soochow University Laboratory of Cancer Molecular Genetics, Suzhou Medical College of Soochow University, Suzhou, China.

AlkB homolog 5 (ALKBH5) has been revealed as a key RNA N -methyladenosine (m A) demethylase that is implicated in development and diseases. However, the function of ALKBH5 in TGF-β-induced epithelial-mesenchymal transition (EMT) and tumor metastasis of non-small-cell lung cancer (NSCLC) remains unknown. Here, we firstly show that ALKBH5 expression is significantly reduced in metastatic NSCLC. ALKBH5 overexpression inhibits TGF-β-induced EMT and invasion of NSCLC cells, whereas ALKBH5 knockdown promotes the corresponding phenotypes. ALKBH5 overexpression suppresses TGF-β-stimulated NSCLC cell metastasis in vivo. ALKBH5 overexpression decreases the expression and mRNA stability of TGFβR2 and SMAD3 but increases those of SMAD6, while ALKBH5 knockdown causes the opposite results. Importantly, ALKBH5 overexpression or knockdown leads respectively to an attenuated or augmented phosphorylation of SMAD3, an indispensable downstream effector that activates TGF-β/SMAD signaling. Moreover, m A-binding proteins YTHDF1/3 promotes TGFβR2 and SMAD3 expression, and YTHDF2 inhibits SMAD6 expression. YTHDF1/2/3 facilitates TGF-β-stimulated EMT and invasion of NSCLC cells. Mechanistically, ALKBH5 affects TGFβR2, SMAD3 and SMAD6 expression and mRNA stability by erasing m A modification in NSCLC cells. ALKBH5 weakens YTHDF1/3-mediated TGFβR2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-β-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism. Taken together, our findings highlight an important role of ALKBH5 in regulating TGF-β/SMAD signaling, and establish a mechanistic interaction of ALKBH5 with TGFβR2/SMAD3/SMAD6 for controlling TGF-β-induced EMT in NSCLCs.
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http://dx.doi.org/10.1096/fj.202200005RRDOI Listing
May 2022

Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention.

Polymers (Basel) 2022 Mar 16;14(6). Epub 2022 Mar 16.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.

MK-2048 is a second-generation integrase inhibitor active against HIV, which has been applied vaginally using ring formulations. In this work, a nanoparticle-in-film technology was developed as a discrete pre-exposure prophylactic product option against HIV for an extended duration of use. A film platform loaded with poly (lactic-co-glycolic acid) nanoparticles (PNP) encapsulating MK-2048 was engineered. MK-2048 PNPs were loaded into films that were manufactured via the solvent casting method. Physicochemical and mechanical properties, in vitro efficacy, compatibility, in vitro and ex vivo permeability, and in vivo pharmacokinetics in macaques were evaluated. PNPs with a mean diameter of 382.2 nm and -15.2 mV zeta potential were obtained with 95.2% drug encapsulation efficiency. PNP films showed comparable in vitro efficacy to free MK-2048 (IC 0.46 vs. 0.54 nM) and were found to have no impact on . MK-2048 encapsulated in PNPs showed an increase in permeability (>4-fold) compared to the free MK-2048 in MDCKII cell lines. Furthermore, PNPs had higher ectocervical tissue permeability (1.7-fold) compared to free MK-2048. PNP films showed sustained drug levels for at least 3 weeks in the macaque vaginal fluid. This work demonstrates the synergy of integrating nanomedicine and polymeric film technology to achieve sustained vaginal drug delivery.
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http://dx.doi.org/10.3390/polym14061196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955144PMC
March 2022

A flexible model-free prediction-based framework for feature ranking.

J Mach Learn Res 2021 May;22

Department of Data Sciences and Operations, Marshall Business School, University of Southern California.

Despite the availability of numerous statistical and machine learning tools for joint feature modeling, many scientists investigate features marginally, i.e., one feature at a time. This is partly due to training and convention but also roots in scientists' strong interests in simple visualization and interpretability. As such, marginal feature ranking for some predictive tasks, e.g., prediction of cancer driver genes, is widely practiced in the process of scientific discoveries. In this work, we focus on marginal ranking for binary classification, one of the most common predictive tasks. We argue that the most widely used marginal ranking criteria, including the Pearson correlation, the two-sample test, and two-sample Wilcoxon rank-sum test, do not fully take feature distributions and prediction objectives into account. To address this gap in practice, we propose two ranking criteria corresponding to two prediction objectives: the classical criterion (CC) and the Neyman-Pearson criterion (NPC), both of which use model-free nonparametric implementations to accommodate diverse feature distributions. Theoretically, we show that under regularity conditions, both criteria achieve sample-level ranking that is consistent with their population-level counterpart with high probability. Moreover, NPC is robust to sampling bias when the two class proportions in a sample deviate from those in the population. This property endows NPC good potential in biomedical research where sampling biases are ubiquitous. We demonstrate the use and relative advantages of CC and NPC in simulation and real data studies. Our model-free objective-based ranking idea is extendable to ranking feature subsets and generalizable to other prediction tasks and learning objectives.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939838PMC
May 2021

Engineered Environment-Friendly Colloidal Core/Shell Quantum Dots for High-Efficiency Solar-Driven Photoelectrochemical Hydrogen Evolution.

ChemSusChem 2022 Mar 23:e202200346. Epub 2022 Mar 23.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, 610054, P. R. China.

"Green" colloidal quantum dots (QDs)-based photoelectrochemical (PEC) cells are promising solar energy conversion systems possessing environmental friendliness, cost-effectiveness, and highly efficient solar-to-hydrogen conversion. In this work, eco-friendly AgInSe (AISe)/ZnSe core/shell QDs with wurtzite (WZ) phase were synthesized for solar hydrogen production. It was demonstrated that appropriately engineering the ZnSe shell thickness resulted in effective surface defects passivation of the AISe core for suppressed charge recombination in the consequent core/shell AISe/ZnSe QDs. The fabricated environmentally friendly core/shell QDs-based PEC device exhibited improved photo-excited electrons extraction efficiency under optimized conditions and delivered a maximum photocurrent density as high as 7.5 mA cm and long-term durability under standard AM 1.5G illumination (100 mW cm ). These findings suggest that AISe/ZnSe core/shell QDs with tailored optoelectronic properties are potential light sensitizers for eco-friendly, cost-effective, and highly efficient solar energy conversion applications.
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http://dx.doi.org/10.1002/cssc.202200346DOI Listing
March 2022

Simultaneous Nitrite Resourcing and Mercury Ion Removal Using MXene-Anchored Goethite Heterogeneous Fenton Composite.

Environ Sci Technol 2022 Apr 22;56(7):4542-4552. Epub 2022 Mar 22.

Hebei Key Lab of Power Plant Flue Gas Multi-Pollutants Control, Department of Environmental Science and Engineering, North China Electric Power University, Baoding 071003, PR China.

The integrated system of gas-phase advanced oxidation process combined with sulfite-based wet absorption process is a desirable method for simultaneous removal of SO, NO, and Hg, but due to the enrichment of nitrite and Hg, resourcing harmless wastewater is still a challenge. To tackle this problem, this study fabricated a bifunctional β[email protected] heterogeneous Fenton material, of which the crystalline phase, morphology, structure, and composition were revealed by using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy-energy dispersive x-ray spectroscopy, and transmission electron microscopy. It exhibits excellent performance on nitrite oxidation (99.5%) and Hg removal (99.7%) and can maintain stable outstanding ability after 13 cycles, with superior Hg adsorption capacity (395 mg/g) and ultralow Fe leaching loss (<0.018 wt %). The synergism between MXene and β-FeOOH appears as follows: (i) MXene, as an inductive agent, directionally converted FeO into β-FeOOH in the hydrothermal method and greatly reduced its monomer size; (ii) the introduced ≡Ti(III)/≡Ti(II) accelerated the regeneration of ≡Fe(II) via rapid electron transfer, thereby improving the heterogeneous Fenton reaction; and (iii) MXene strongly immobilized β-FeOOH to greatly inhibit Fe-leaching. HO, O, and O were the main radicals identified by electron spin resonance. Radical quenching tests showed their contributions to NO oxidation in the descending order HO > O > O. Quantum chemical calculations revealed that OH-induced oxidation of NO or HNO was the primary reaction path. Density functional theory calculations combined with X-ray photoelectron spectroscopy and Raman characterizations displayed the Hg removal mechanism, with HgCl, HgCl, and HgO as the main byproducts. This novel material provides a new strategy for resourcing harmless wastewater containing nitrite and Hg.
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http://dx.doi.org/10.1021/acs.est.2c00786DOI Listing
April 2022

Hepatoprotective Role of 4-Octyl Itaconate in Concanavalin A-Induced Autoimmune Hepatitis.

Mediators Inflamm 2022 11;2022:5766434. Epub 2022 Mar 11.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

4-Octyl itaconate (OI) is a novel anti-inflammatory metabolite that exerts protective effects in many various disease models. However, its function in autoimmune hepatitis- (AIH-) associated hepatic injury has not been investigated. In this study, we successfully used concanavalin A (Con A) to establish an AIH-associated liver injury model. Furthermore, we investigated the effect of OI in Con A-induced liver injury and found that OI mitigated Con A-induced histopathological damage. OI administration reduced serum levels of alanine transaminase and aspartate transaminase in Con A-treated mice and attenuated the infiltration of macrophages induced by Con A. Moreover, OI effectively inhibited the expression of proinflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-), interferon-gamma (IFN-), and IL-1 induced by Con A. Furthermore, OI decreased hepatocyte apoptosis and malondialdehyde levels and increased the reduced glutathione/oxidized glutathione ratio in the Con A-induced liver injury model. In addition, we found that OI inhibited Con A-induced hepatocyte apoptosis in vitro, while Nrf2 deletion eliminated this effect. Furthermore, we administrated the Nrf2 inhibitor ML385 in OI+Con A-treated mice and found that ML385 eliminated the protective effect of OI in vivo. In addition, OI inhibited Con A-induced activation of nuclear factor-kappa B (NF-𝜅B) and the expression of proinflammatory cytokines in macrophages. Therefore, OI protected mice from Con A-induced liver damage and may be associated with Nrf2 activation and NF-𝜅B inhibition. Finally, our study revealed that OI inhibited TNF-, or supernatants from Con A-treated RAW264.7 cells induced hepatocyte apoptosis. In conclusion, our study indicated that OI alleviated Con A-induced hepatic damage by reducing inflammatory response, oxidative stress, and apoptosis.
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http://dx.doi.org/10.1155/2022/5766434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933104PMC
March 2022

Global urban environmental change drives adaptation in white clover.

Science 2022 03 17;375(6586):1275-1281. Epub 2022 Mar 17.

Department of Biology, Washington University in St. Louis, St. Louis, MO, USA.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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http://dx.doi.org/10.1126/science.abk0989DOI Listing
March 2022

Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines.

Sci Transl Med 2022 Apr 27;14(642):eabn9243. Epub 2022 Apr 27.

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02138, USA.

The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.
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http://dx.doi.org/10.1126/scitranslmed.abn9243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995028PMC
April 2022

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis.

J Bone Miner Res 2022 May 28;37(5):1044-1055. Epub 2022 Mar 28.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, School of Stomatology, the Fourth Military Medical University, Xi'an, PR China.

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4542DOI Listing
May 2022

How Do We Jump-Start Self-measured Blood Pressure Monitoring in the United States? Addressing Barriers Beyond the Published Literature.

Am J Hypertens 2022 03;35(3):244-255

Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Hypertension is highly prevalent in the United States, and many persons with hypertension do not have controlled blood pressure. Self-measured blood pressure monitoring (SMBP), when combined with clinical support, is an evidence-based strategy for lowering blood pressure and improving control in persons with hypertension. For years, there has been support for widespread implementation of SMBP by national organizations and the federal government, and SMBP was highlighted as a primary intervention in the 2020 Surgeon General's Call to Action to Control Hypertension, yet optimal SMBP use remains low. There are well-known patient and clinician barriers to optimal SMBP documented in the literature. We explore additional high-level barriers that have been encountered, as broad policy and systems-level changes have been attempted, and offer potential solutions. Collective efforts could modernize data transfer and processing, improve broadband access, expand device coverage and increase affordability, integrate SMBP into routine care and reimbursement practices, and strengthen patient engagement, trust, and access.
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http://dx.doi.org/10.1093/ajh/hpab170DOI Listing
March 2022

Non-clinical immunogenicity, biodistribution and toxicology evaluation of a chimpanzee adenovirus-based COVID-19 vaccine in rat and rhesus macaque.

Arch Toxicol 2022 05 28;96(5):1437-1453. Epub 2022 Feb 28.

Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, Jiangsu, 211198, People's Republic of China.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 has rapidly expanded into a serious global pandemic. Due to the high morbidity and mortality of COVID-19, there is an urgent need to develop safe and effective vaccines. AdC68-19S is an investigational chimpanzee adenovirus serotype 68 (AdC68) vector-based vaccine which encodes the full-length spike protein of SARS-CoV-2. Here, we evaluated the immunogenicity, biodistribution and safety profiles of the candidate vaccine AdC68-19S in Sprague Dawley (SD) rat and rhesus macaque under GLP conditions. To characterize the biodistribution profile of AdC68-19S, SD rats were given a single intramuscular injection of AdC68-19S 2 × 10 VP/dose. Designated organs were collected on day 1, day 2, day 4, day 8 and day 15. Genomic DNA was extracted from all samples and was further quantified by real-time quantitative polymerase chain reaction (qPCR). To characterize the toxicology and immunogenicity profiles of AdC68-19S, the rats and rhesus macaques were injected intramuscularly with AdC68-19S up to 2 × 10vp/dose or 4 × 10vp/dose (2 and fourfold the proposed clinical dose of 1 × 10vp/dose) on two or three occasions with a 14-day interval period, respectively. In addition to the conventional toxicological evaluation indexes, the antigen-specific cellular and humoral responses were evaluated. We proved that multiple intramuscular injections could elicit effective and long-lasting neutralizing antibody responses and Th1 T cell responses. AdC68-19S was mainly distributed in injection sites and no AdC68-19S related toxicological reaction was observed. In conclusion, these results have shown that AdC68-19S could induce an effective immune response with a good safety profile, and is a promising candidate vaccine against COVID-19.
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http://dx.doi.org/10.1007/s00204-021-03221-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883008PMC
May 2022

[Effect of acupuncture at Huatuo Jiaji (EX-B2) combined with core muscle training on motor function of lower limbs in patients with hemiplegia after stroke].

Zhen Ci Yan Jiu 2022 Feb;47(2):154-9

The Second Department of Rehabilitation, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061.

Objective: To observe the effect of acupuncture at Huatuo Jiaji (EX-B2) combined with core muscle training on motor function of lower limbs, balance function and core muscle in patients with hemiplegia after stroke.

Methods: A total of ninety-six patients with hemiplegia after stroke were randomly and equally divided into acupuncture, training and combination groups (=32 cases in each). Patients of the acupuncture group were given acupuncture at the 5, 7, 9 and 11 chest vertebrae, and the 1 to 5 lumbar vertebrae of EX-B2. Patients in the training group received core muscle training. In the combination group, both acupuncture treatment and core muscle training were given to the patients. The treatment was conducted once daily, 5 times a week for 4 weeks. The Fugl-Meyer lower limb motor function score (FMA), Berg balance function scale (BBS), Barthel index (BI) and surface electromyography (sEMG) of the erector spinae and rectus abdominis were evaluated before and after treatment and during the follow-up period.

Results: Compared with the scores before the treatment, the FMA, BBS and BI scores were obviously increased after the treatment and during the follow-up period in the three groups respectively (<0.05). After treatment and during the follow-up period, the root mean square (RMS) of erector spinae and rectus abdominis in the sitting position flexed 45° and extended 30° on the healthy and affected side were higher than those of the same side before treatment in the three groups (<0.05). The therapeutic effect of combination of acupuncture at EX-B2 and core muscle training was obviously superior to that of single acupuncture or single training (<0.05). Before the treatment, the RMS of erector spinae and rectus abdominis in the sitting position flexed 45° and extended 30° on the affected side were lower than those of the healthy side in the three groups (<0.05), while there was no significant difference between the RMS of the erector spinae and rectus abdominis of the affected side and the healthy side in the comprehensive group after treatment and during the follow-up period (P>0.05).

Conclusion: Acupuncture at EX-B2 combined with core muscle training can significantly improve the balance function and lower limb motor function of patients with hemiplegia after stroke.
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http://dx.doi.org/10.13702/j.1000-0607.20210487DOI Listing
February 2022

Analysis of Insulin Resistance in Nonalcoholic Steatohepatitis.

Methods Mol Biol 2022 ;2455:233-241

Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.

Insulin resistance is a major phenotype observed in nonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease (NAFLD). Insulin resistance in NASH is characterized by reductions in whole body, hepatic, and adipose tissue insulin sensitivity. The mechanisms underlying hepatic insulin resistance is primarily associated with hepatic glucose production (HGP) rate. Hepatic insulin resistance can also be a consequence or a driving factor of hepatic lipid accumulation by increasing free fatty acid synthesis, delivery, and catabolism. The common method to assess hepatic insulin resistance is to measure hepatic glucose production (HGP) using isotope tracer distribution technique. However, non-radioactive approaches have been developed to assess hepatic insulin resistance in the context of NASH. In this chapter, we describe the methods to evaluate hepatic insulin resistance in animal models of NASH by examining insulin sensitivity and glucose tolerance as well as the key molecules in hepatic insulin signaling pathways.
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http://dx.doi.org/10.1007/978-1-0716-2128-8_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053411PMC
March 2022

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus.

Biomed Res Int 2022 15;2022:1040129. Epub 2022 Feb 15.

School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Background: Traditional Chinese medicine Yinhuapinggan granule (YHPG) has been used for treating upper respiratory tract infection like influenza, cough, and viral pneumonia. However, its active ingredients that really exert the main efficacy have not been well elucidated. This study is aimed at screening its antiviral components and investigating the potential therapeutic mechanisms of YHPG against the influenza A/PR8/34 (H1N1) virus in Madin Darby canine kidney (MDCK).

Methods: MDCK cells were infected with the influenza virus and then treated with ribavirin, YHPG, and main active ingredients in YHPG. Based on the maximum nontoxic concentration (TC), half-maximal toxic concentration (TC), half-maximal inhibitory concentration (IC), and therapeutic index (TI), interferon- (IFN-) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the gene expression of TLR7, MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Jun amino terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and p65 nuclear transcription factor-kappa B (p65 NF-B) was quantified using reverse transcription-polymerase chain reaction (RT-PCR).

Results: The results indicated that the components of YHPG, such as ephedrine hydrochloride, pseudoephedrine hydrochloride, chlorogenic acid, and emodin, had significant antiviral effects. High and medium doses of YHPG effectively reduced the cytopathic effect (CPE) and significantly decreased IFN- and IL-6 levels in the supernatant. Simultaneously, the transcript levels of TLR7, MyD88, TRAF6, JNK, p38 MAPK, and p65 NF-B decreased in infected MDCK cells. Moreover, a certain dose-dependent relationship among different groups of YHPG was observed.

Conclusions: These results indicated that YHPG and the components of YHPG had a significant inhibitory function on the proliferation of the H1N1 virus. The mechanism might be associated with suppressing the activation of the TLR7/MyD88 signaling pathway, a decrease in the mRNA expression of key target genes, and inhibition of IFN- and IL-6 secretion.
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http://dx.doi.org/10.1155/2022/1040129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863447PMC
March 2022

Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity.

iScience 2022 Feb 2;25(2):103859. Epub 2022 Feb 2.

Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.

RING finger protein186 (RNF186) is dramatically upregulated in steatotic livers. The physiological role of RNF186 in non-alcoholic fatty liver disease (NAFLD) remains obscure. Here, we found that hepatocyte-specific RNF186 knockout (RNF186 ) mice were protected from HFD-induced obesity. RNF186 ablation in liver suppressed inflammatory responses and ER stress and alleviated insulin tolerance, leading to improved glucose and lipid metabolism under HFD conditions. RNA-seq and western blot analyses revealed a significant downregulation of peroxisome proliferator-activated receptor γ, stearoyl-CoA desaturase 1, and cluster of differentiation 36 in the liver of RNF186 knockout mice consuming HFD. RNF186 deletion in liver results in less weight gain during HFD feeding and is associated with reduced liver fat, inflammation, and improved glucose and insulin tolerance. In contrast, upregulation of RNF186 in C57BL/6J mice livers impaired lipid metabolism and insulin tolerance. The collective results suggest that RNF186 may be a potential regulator of NAFLD in obesity.
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http://dx.doi.org/10.1016/j.isci.2022.103859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850801PMC
February 2022

VirtualCube: An Immersive 3D Video Communication System.

IEEE Trans Vis Comput Graph 2022 May 8;28(5):2146-2156. Epub 2022 Apr 8.

The VirtualCube system is a 3D video conference system that attempts to overcome some limitations of conventional technologies. The key ingredient is VirtualCube, an abstract representation of a real-world cubicle instrumented with RGBD cameras for capturing the user's 3D geometry and texture. We design VirtualCube so that the task of data capturing is standardized and significantly simplified, and everything can be built using off-the-shelf hardware. We use VirtualCubes as the basic building blocks of a virtual conferencing environment, and we provide each VirtualCube user with a surrounding display showing life-size videos of remote participants. To achieve real-time rendering of remote participants, we develop the V-Cube View algorithm, which uses multi-view stereo for more accurate depth estimation and Lumi-Net rendering for better rendering quality. The VirtualCube system correctly preserves the mutual eye gaze between participants, allowing them to establish eye contact and be aware of who is visually paying attention to them. The system also allows a participant to have side discussions with remote participants as if they were in the same room. Finally, the system sheds lights on how to support the shared space of work items (e.g., documents and applications) and track participants' visual attention to work items.
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http://dx.doi.org/10.1109/TVCG.2022.3150512DOI Listing
May 2022
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