Publications by authors named "Zheng Liu"

2,062 Publications

  • Page 1 of 1

Engineering DNAzyme strategies for fluorescent detection of lead ions based on RNA cleavage-propelled signal amplification.

J Hazard Mater 2022 Aug 3;440:129712. Epub 2022 Aug 3.

Department of Food Quality and Safety, Jilin University, Changchun 130062, China. Electronic address:

Based on the high recognition ability and flexible programmability of GR5 DNAzyme, two fluorescent biosensors were engineered for amplified detection of Pb via incorporating TiCT MXenes and embedding 2-aminopurine (2-AP), respectively. The quencher-required approach relied on the DNA affinity and fluorescence quenching ability of TiCT MXenes. Benefiting from the low background signal modulated by TiCT MXenes, the sensitive determination of Pb was achieved in the linear range of 0.2-10 ng mL with the limit of detection (LOD) of 0.05 ng mL. The quencher-free approach combined the fluorescent trait of 2-AP embedded in DNA structure, and the RNA cleavage-propelled digestion process of Exonuclease I (Exo I) for signal amplification, indicating the sensitive detection of Pb with the LOD as low as 0.02 ng mL in the linear range of 0.1-10 ng mL. Both DNAzyme assays exhibited simple procedures, favorable specificity, rapid analysis, and satisfactory application in standard reference materials (lead in drinking water) and spiked water samples. The two fluorescent biosensors established in this work would not only provide theoretic fundament for DNA adsorption of TiCT MXenes and the design of 2-AP-embedded DNAzyme assays, but also hold a great potential for on-site monitoring of lead pollution in water samples.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129712DOI Listing
August 2022

Electrically tunable two-dimensional heterojunctions for miniaturized near-infrared spectrometers.

Nat Commun 2022 Aug 8;13(1):4627. Epub 2022 Aug 8.

Key Laboratory of Optoelectronics Technology, Ministry of Education, Faculty of Information Technology, Beijing University of Technology, Beijing, 100124, China.

Miniaturized spectrometers are of considerable interest for their portability. Most designs to date employ a photodetector array with distinct spectral responses or require elaborated integration of micro & nano optic modules, typically with a centimeter-scale footprint. Here, we report a design of a micron-sized near-infrared ultra-miniaturized spectrometer based on two-dimensional van der Waals heterostructure (2D-vdWH). By introducing heavy metal atoms with delocalized electronic orbitals between 2D-vdWHs, we greatly enhance the interlayer coupling and realize electrically tunable infrared photoresponse (1.15 to 1.47 μm). Combining the gate-tunable photoresponse and regression algorithm, we achieve spectral reconstruction and spectral imaging in a device with an active footprint < 10 μm. Considering the ultra-small footprint and simple fabrication process, the 2D-vdWHs with designable bandgap energy and enhanced photoresponse offer an attractive solution for on-chip infrared spectroscopy.
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http://dx.doi.org/10.1038/s41467-022-32306-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360404PMC
August 2022

Sarcopenic obesity and therapeutic outcomes in gastrointestinal surgical oncology: A meta-analysis.

Front Nutr 2022 22;9:921817. Epub 2022 Jul 22.

Department of Thoracic Surgery, Thoracic Oncology Institute, Peking University People's Hospital, Beijing, China.

Background: Sarcopenic obesity (SO) has been indicated as a scientific and clinical priority in oncology. This meta-analysis aimed to investigate the impacts of preoperative SO on therapeutic outcomes in gastrointestinal surgical oncology.

Methods: We searched the PubMed, EMBASE, and Cochrane Library databases through March 4th 2022 to identify cohort studies. Endpoints included postoperative complications and survival outcomes. Newcastle Ottawa Scale was used for quality assessment. Heterogeneity and publication bias were assessed. Subgroup analyses and sensitivity analyses were performed.

Results: Twenty-six studies (8,729 participants) with moderate to good quality were included. The pooled average age was 65.6 [95% confidence interval (CI) 63.7-67.6] years. The significant heterogeneity in SO definition and diagnosis among studies was observed. Patients with SO showed increased incidences of total complications (odds ratio 1.30, 95% CI: 1.03-1.64, = 0.030) and major complications (Clavien-Dindo grade ≥ IIIa, odds ratio 2.15, 95% CI: 1.39-3.32, = 0.001). SO was particularly associated with the incidence of cardiac complications, leak complications, and organ/space infection. SO was also predictive of poor overall survival (hazard ratio 1.73, 95% CI: 1.46-2.06, < 0.001) and disease-free survival (hazard ratio 1.41, 95% CI: 1.20-1.66, < 0.001). SO defined as sarcopenia in combination with obesity showed greater association with adverse outcomes than that defined as an increased ratio of fat mass to muscle mass. A low prevalence rate of SO (< 10%) was associated with increased significance for adverse outcomes compared to the high prevalence rate of SO (> 20%).

Conclusion: The SO was associated with increased complications and poor survival in gastrointestinal surgical oncology. Interventions aiming at SO have potentials to promote surgery benefits for patients with gastrointestinal cancers. The heterogeneity in SO definition and diagnosis among studies should be considered when interpreting these findings.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255286], identifier [CRD42021255286].
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http://dx.doi.org/10.3389/fnut.2022.921817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355157PMC
July 2022

Acylglycerol kinase promotes ovarian cancer progression and regulates mitochondria function by interacting with ribosomal protein L39.

J Exp Clin Cancer Res 2022 Aug 8;41(1):238. Epub 2022 Aug 8.

Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, 571101, Hainan, China.

Background: Epithelial ovarian cancer (EOC) is the leading cause of deaths among patients with gynecologic malignancies. In recent years, cancer stem cells (CSCs) have attracted great attention, which have been regarded as new biomarkers and targets in cancer diagnoses as well as therapies. However, therapeutic failure caused by chemotherapy resistance in late-stage EOC occurs frequently. The 5-year survival rate of patients with EOC remains at about 30%.

Methods: In this study, the expression of acylglycerol kinase (AGK) was analyzed among patients with EOC. The effect of AGK on EOC cell proliferation and tumorigenicity was studied using Western blotting, flow cytometry, EdU assay and in vivo xenotransplantation assays. Furthermore, AGK induced CSC-like properties and was resistant to cisplatin chemotherapy in the EOC cells, which were investigated through sphere formation assays and the in vivo model of chemoresistance. Finally, the relationship between AGK and RPL39 (Ribosomal protein L39) in mitochondria as well as their effect on the mitochondrial function was analyzed through methods including transmission electron microscopy, microarray, biotin identification and immunoprecipitation.

Results: AGK showed a markedly upregulated expression in EOC, which was significantly associated with the poor survival of patients with EOC, the expression of AGK-promoted EOC cell proliferation and tumorigenicity. AGK also induced CSC-like properties in the EOC cells and was resistant to cisplatin chemotherapy. Furthermore, the results indicated that AGK not only maintained mitochondrial cristae morphogenesis, but also increased the production of reactive oxygen species and Δψm of EOC cells in a kinase-independent manner. Finally, our results revealed that AGK played its biological function by directly interacting with RPL39.

Conclusions: We demonstrated that AGK was a novel CSC biomarker for EOC, which the stemness of EOC was promoted and chemotherapy resistance was developed through physical as well as functional interaction with RPL39.
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http://dx.doi.org/10.1186/s13046-022-02448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358817PMC
August 2022

Corrigendum for "Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns".

Authors:
Li-Li Shi Zheng Liu

Allergy 2022 Aug;77(8):2576-2577

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

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http://dx.doi.org/10.1111/all.15335DOI Listing
August 2022

Alleviating experimental allergic eye disease by inhibiting pro-lymphangiogenic VEGFR3 signal.

Ocul Surf 2022 Aug 2;26:1-12. Epub 2022 Aug 2.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China. Electronic address:

Purpose: Ocular allergy leads to acute and chronic inflammation that may deteriorate the conjunctiva and other ocular tissue. The conjunctiva is covered with abundant lymphatic vessels but how the conjunctival lymphatic system patriciates in the development of allergic eye disease (AED) remains to be elucidated.

Methods And Results: By using ovalbumin (OVA)+pertussis toxin (PTX) as a sensitizer followed by daily OVA challenges, we induced optimized AED manifestations in mice. We show that conjunctival lymphatics underwent significant expansion after 28 days of chronic OVA challenge, and this process can be prevented by inducible genetic ablation of lymphatic Vegfr3. Through transcriptomic profile analysis in combination with histopathological examinations, we found that pro-lymphangiogenic VEGFR3 signal promoted allergy-induced activation of T helper 2 (Th2) type immune responses, including antigen presentation, and Th2 cells, B cells and mast cell-related pathways in the conjunctiva, thereby critically contributing to the immunoglobulin E (IgE) production and AED manifestations. As a result, ocular allergy can be alleviated by genetic inhibition of lymphatic Vegfr3. Interestingly, pro-lymphangiogenic VEGFR3 signal did not appear to affect the obstruction of meibomian glands (MGs) or the activation of Th17 type and neutrophil pathways that are associated with AED.

Conclusions: These data reveal the key role of pro-lymphangiogenic VEGFR3 signaling in the development of AED and provide experimental evidence that VEGFR3 inhibition may be useful in treating ocular allergy in patients.
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http://dx.doi.org/10.1016/j.jtos.2022.07.002DOI Listing
August 2022

Surgical outcomes and sexual function after laparoscopic colon cancer surgery with transvaginal versus conventional specimen extraction: A retrospective propensity score matched cohort study.

Int J Surg 2022 Jul 31;104:106787. Epub 2022 Jul 31.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, NO.17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China. Electronic address:

Background: Natural orifice specimen extraction has been shown to reduce postoperative pain and wound complications, and provide better cosmetic outcome. However, whether transvaginal specimen extraction affects sexual function remains controversial. The purpose of this study was to investigate the short-term outcomes, sexual function, cosmetic outcomes and prognosis after colon cancer surgery with transvaginal specimen extraction.

Method: This study was a propensity score-matched comparative retrospective study, based on prospectively collected data in a single center. This study included 70 pairs of propensity score-matched female patients who underwent laparoscopic curative resection for stage I-III colon cancer with transvaginal specimen extraction and conventional specimen extraction between November 2015 and November 2020. Covariates used in the propensity score included age, tumor diameter, tumor differentiation, T stage and American Joint Committee on Cancer stage. Outcome measures included postoperative complication, postoperative sexual function, cosmetic result, disease-free survival and overall survival.

Results: Patients in transvaginal group were administered with less additional analgesics (P = 0.008), and had fewer wound complications (P = 0.028). None of patient in the two groups underwent anastomotic leakage, incisional disruption or vaginal fistula. The baseline pre-operative Female Sexual Function Index scores in two groups were the same, and no difference was found in postoperative score between the two groups (P = 0.790). The cosmetic score was significantly better in transvaginal group than that of conventional laparoscopy group (P = 0.000). During the follow-up period, there were no differences in OS or DFS between the two groups (P = 0.658, P = 0.663).

Conclusions: Compared with laparoscopic colon cancer radical resection with specimen extraction, transvaginal specimen extraction is oncologically safe, brings better short-term outcomes, improved cosmetic results and has limited adverse effect on female's sexual function. This procedure can be further carried out in more appropriate patients.
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http://dx.doi.org/10.1016/j.ijsu.2022.106787DOI Listing
July 2022

Mesoscale visualization of three-dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes.

Theranostics 2022 11;12(12):5418-5433. Epub 2022 Jul 11.

Britton Chance Center and MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes. Whole-mount imaging at mesoscale revealed that the hepatic classical lobule preferred the oblate ellipsoid morphology in the mouse liver and exhibited hepatic sinusoids with heterogeneous arrangement and intricate loop structure. Liver fibrosis not only induces sinusoidal density increase but also promotes sinusoidal arrangement with increased sinusoidal branch and loop structure. Meanwhile, we found that CD11c DCs followed a lognormal distribution in the hepatic lobules, skewing toward lobular boundary in steady state. CCl-induced chronic liver injury promoted CD11c DC rearrangement at the lobular border before the formation of liver fibrosis. Furthermore, through whole-mount imaging of tumor-immune cell-vascular crosstalk in intact lobes based on liver-CUBIC, we characterized an accumulation of CX3CR1CCR2F4/80 macrophages at metastatic foci in early colorectal liver metastases. Importantly, colorectal cells secrete CCL2 to mobilize CX3CR1CCR2F4/80 macrophages to accumulate at liver micrometastases, and the interruption of CCL2-induced macrophage accumulation inhibits early colonization of metastasis in the liver. Our investigation of the sinusoidal network and DC/macrophage arrangements through the liver-CUBIC approach and whole-mount imaging provide a powerful platform for understanding hepatic circulatory properties and immune surveillance in the liver.
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http://dx.doi.org/10.7150/thno.71718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330531PMC
August 2022

Mesoscale visualization of three-dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes.

Theranostics 2022 11;12(12):5418-5433. Epub 2022 Jul 11.

Britton Chance Center and MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes. Whole-mount imaging at mesoscale revealed that the hepatic classical lobule preferred the oblate ellipsoid morphology in the mouse liver and exhibited hepatic sinusoids with heterogeneous arrangement and intricate loop structure. Liver fibrosis not only induces sinusoidal density increase but also promotes sinusoidal arrangement with increased sinusoidal branch and loop structure. Meanwhile, we found that CD11c DCs followed a lognormal distribution in the hepatic lobules, skewing toward lobular boundary in steady state. CCl-induced chronic liver injury promoted CD11c DC rearrangement at the lobular border before the formation of liver fibrosis. Furthermore, through whole-mount imaging of tumor-immune cell-vascular crosstalk in intact lobes based on liver-CUBIC, we characterized an accumulation of CX3CR1CCR2F4/80 macrophages at metastatic foci in early colorectal liver metastases. Importantly, colorectal cells secrete CCL2 to mobilize CX3CR1CCR2F4/80 macrophages to accumulate at liver micrometastases, and the interruption of CCL2-induced macrophage accumulation inhibits early colonization of metastasis in the liver. Our investigation of the sinusoidal network and DC/macrophage arrangements through the liver-CUBIC approach and whole-mount imaging provide a powerful platform for understanding hepatic circulatory properties and immune surveillance in the liver.
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http://dx.doi.org/10.7150/thno.71718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330531PMC
August 2022

Sex-Biased Immune Responses to Antibiotics during Anti-PD-L1 Treatment in Mice with Colon Cancer.

J Immunol Res 2022 19;2022:9202491. Epub 2022 Jul 19.

Department of Chemical Engineering, Tsinghua University, 100084 Beijing, China.

Colitis is a frequently occurred side effect of immune checkpoint inhibitors (ICIs), which are increasingly used in cancer treatment, whereas antibiotics are widely used to treat colitis, their effectiveness in ICI-associated colitis remains controversial. In this study, we firstly assessed the effectiveness of several commonly used antibiotics and antibiotic cocktails in alleviating of dextran sulfate sodium- (DSS-) induced colitis. We observed that two narrow-spectrum antibiotics, neomycin and metronidazole, were more effective in alleviating colitis, as evidenced by the remission of loss of the body weight, enlargement of the spleen, shortening of the colon, secretion of proinflammatory cytokines, and histological score of the colon tissue. Moreover, these two antibiotics resulted in better relief of colitis symptoms in the MC38 tumor-bearing male mice receiving the anti-PD-L1 mAb (PD-L1) treatment, compared to the females. In the meantime, an enhanced response to PD-L1 efficiency against mice colon cancer was observed in the male mouse group upon the application of these two antibiotics. In contrast, both neomycin and metronidazole showed destructive effects on the antitumor efficiency of PD-L1 in female mice, despite relief from colitis. We found that antibiotic treatment attenuated the increased infiltration of granulocytes and myeloid cells in colon tissue induced by DSS in female mice, while reducing the proportion of Th17 cells in male mice. These differences were further associated with the sex-biased differences in the gut microbiota. These findings indicated that sex-dependent alterations in the gut microbiota should be considered when applying antibiotics for the treatment of ICI-associated colitis.
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http://dx.doi.org/10.1155/2022/9202491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325566PMC
August 2022

K2P1 leak cation channels contribute to ventricular ectopic beats and sudden death under hypokalemia.

FASEB J 2022 Aug;36(8):e22455

Department of Biological Sciences, University at Albany, State University of New York, Albany, New York, USA.

Hypokalemia causes ectopic heartbeats, but the mechanisms underlying such cardiac arrhythmias are not understood. In reduced serum K concentrations that occur under hypokalemia, K2P1 two-pore domain K channels change ion selectivity and switch to conduct inward leak cation currents, which cause aberrant depolarization of resting potential and induce spontaneous action potential of human cardiomyocytes. K2P1 is expressed in the human heart but not in mouse hearts. We test the hypothesis that K2P1 leak cation channels contribute to ectopic heartbeats under hypokalemia, by analysis of transgenic mice, which conditionally express induced K2P1 specifically in hearts, mimicking K2P1 channels in the human heart. Conditional expression of induced K2P1 specifically in the heart of hypokalemic mice results in multiple types of ventricular ectopic beats including single and multiple ventricular premature beats as well as ventricular tachycardia and causes sudden death. In isolated mouse hearts that express induced K2P1, sustained ventricular fibrillation occurs rapidly after perfusion with low K concentration solutions that mimic hypokalemic conditions. These observed phenotypes occur rarely in control mice or in the hearts that lack K2P1 expression. K2P1-expressing mouse cardiomyocytes of transgenic mice much more frequently fire abnormal single and/or rhythmic spontaneous action potential in hypokalemic conditions, compared to wild type mouse cardiomyocytes without K2P1 expression. These findings confirm that K2P1 leak cation channels induce ventricular ectopic beats and sudden death of transgenic mice with hypokalemia and imply that K2P1 leak cation channels may play a critical role in human ectopic heartbeats under hypokalemia.
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http://dx.doi.org/10.1096/fj.202200707RDOI Listing
August 2022

Long intergenic noncoding RNA LINC01287 drives the progression of cervical cancer via regulating miR-513a-5p/SERP1.

Hum Cell 2022 Jul 27. Epub 2022 Jul 27.

Molecular Pharmacology Laboratory, Department of Clinical Pharmacy, Xiangtan Center Hospital, Heping Street 120, Xiangtan, 411100, China.

Cervical cancer is one of the most frequent types of cancer in women, which is characterized by high invasion and metastatic tendency in its advanced stage. Emerging evidence indicated that long non-coding RNAs (LncRNAs) are involved in the pathogenesis of cervical cancer. LINC01287 has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, up until now, whether LINC01287 is associated with the initiation and development of cervical cancer remains largely unknown. In the present study, expression levels of LINC01287, miR-513a-5p and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA were quantified utilizing qRT-PCR. A series of functional experiments including CCK-8 assay, colony formation assay, transwell assay, flow cytometry, and tumor xenograft growth of cervical cancer cells were performed for studying the effects of LINC01287. The luciferase reporter assay, pull-down assay, and western blot were used to confirm the downstream targets of LINC01287 and miR-513a-5p. The results demonstrate that LINC01287 was highly expressed in cervical cancer tissue samples and cell lines. High LINC01287 predicts a poor prognosis for cervical cancer patients. Additional gain- and loss-of-function experiments demonstrated that silencing LINC01287 inhibited cervical cancer cells proliferation, colony formation, migration, apoptosis in vitro and retarded tumor growth and metastasis in vivo. Furthermore, the dual-luciferase reporter gene system and RNA pulldown assay validated that LINC01287 positively regulated SERP1 expressions by sponging miR-513a-5p, and LINC01287 inhibited cervical cancer progression by regulating miR-513a-5p/SERP1 axis. In conclusion, the current study first identified that LINC01287/miR-513a-5p/SERP1 axis played an important role in cervical cancer progression. LINC01287 might be a prognostic biomarker and a target for new therapies in patients with cervical cancer.
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http://dx.doi.org/10.1007/s13577-022-00755-9DOI Listing
July 2022

How I do it: biportal endoscopic spinal surgery for revision of adjacent segment disease after instrumented lumbar fusion.

Acta Neurochir (Wien) 2022 Jul 26. Epub 2022 Jul 26.

Department of Orthopedics, Peking University Shougang Hospital, Shijingshan District, No. 9, Jinyuanzhuang Rd, Beijing, 100144, China.

Background: Lumbar fusion with rigid fixation can be complicated by adjacent segment degeneration, which may cause neurological deficits and back pain, and occasionally necessitates revision surgery. This type of revision surgery is difficult to perform in a minimally invasive manner because it requires the revision of the original internal fixation instruments.

Method: We describe a biportal endoscopic spinal surgery (BESS) procedure for revision surgery due to adjacent segment disease after lumbar fusion with rigid fixation instruments. The radiological images and complete surgical procedure are presented.

Conclusions: BESS effectively enabled nerve decompression, intervertebral fusion, and revision of lumbar fusion with fixation instruments in a minimally invasive manner.
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http://dx.doi.org/10.1007/s00701-022-05318-3DOI Listing
July 2022

Room-temperature epitaxial welding of 3D and 2D perovskites.

Nat Mater 2022 Jul 25. Epub 2022 Jul 25.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing, China.

Formation of epitaxial heterostructures via post-growth self-assembly is important in the design and preparation of functional hybrid systems combining unique properties of the constituents. This is particularly attractive for the construction of metal halide perovskite heterostructures, since their conventional solution synthesis usually leads to non-uniformity in composition, crystal phase and dimensionality. Herein, we demonstrate that a series of two-dimensional and three-dimensional perovskites of different composition and crystal phase can form epitaxial heterostructures through a ligand-assisted welding process at room temperature. Using the CsPbBr/PEAPbBr heterostructure as a demonstration, in addition to the effective charge and energy transfer across the epitaxial interface, localized lattice strain was observed at the interface, which was extended to the top layer of the two-dimensional perovskite, leading to multiple new sub-bandgap emissions at low temperature. Given the versatility of our strategy, unlimited hybrid systems are anticipated, yielding composition-, interface- and/or orientation-dependent properties.
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http://dx.doi.org/10.1038/s41563-022-01311-4DOI Listing
July 2022

Olfactory cleft mucus galectin-10 predicts olfactory loss in chronic rhinosinusitis.

Ann Allergy Asthma Immunol 2022 Jul 21. Epub 2022 Jul 21.

Department of Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, People's Republic of China. Electronic address:

Background: Eosinophils have been reported to be involved in the pathogenesis of olfactory fluctuation in chronic rhinosinusitis (CRS). Galectin-10 is more frequently associated with type 2 inflammation and potentially a sign of intense eosinophil activation.

Objective: To explore olfactory cleft mucus and olfactory mucosa galectin-10 level and its association with olfactory dysfunction (OD) in CRS.

Methods: We prospectively enrolled 50 patients with CRS and 15 healthy controls. Olfactory cleft mucus and superior turbinate biopsy specimens were collected to analyze galectin-10 levels and quantify tissue eosinophils. Psychophysical olfactory testing, olfactory cleft endoscopy scale, and olfactory cleft computed tomography scores were obtained. The predictability of galectin-10 levels for OD in patients with CRS was analyzed by multivariable logistic regression analysis.

Results: Both olfactory cleft mucus and olfactory mucosa galectin-10 levels in patients with CRS with OD were significantly higher than those in patients with CRS without OD (all P < .001). Mucus galectin-10 levels were positively correlated with tissue eosinophils (r = 0.541, P = 0.002), olfactory cleft endoscopy scale (r = 0.498, P = 0.006), and olfactory cleft computed tomography scores (r = 0.432, P = 0.019) in patients with CRS. Mucus galectin-10 levels were negatively correlated threshold, discrimination, and identification (r = -0.589,  P = 0.001), olfactory threshold (r = -0.522, P = 0.003), olfactory discrimination (r = -0.488, P = 0.007), and olfactory identification (r = -0.466, P = 0.011) scores. After adjusting for patient demographics and comorbidities, mucus galectin-10 levels were significantly associated with OD in patients with CRS (odds ratio, 1.299; P = .008). Mucus galectin-10 levels greater than 8.975 ng/mL were the best predictor of OD in CRS.

Conclusion: Olfactory cleft mucus galectin-10 is highly associated with OD in CRS.
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http://dx.doi.org/10.1016/j.anai.2022.07.014DOI Listing
July 2022

Case Report: Five-Level Unilateral Laminectomy Bilateral Decompression (ULBD) by Two-Stage Unilateral Biportal Endoscopy (UBE).

Front Surg 2022 5;9:944509. Epub 2022 Jul 5.

Department of Orthopedics, Shougang Hospital, Health Science Centre, Peking University, Beijing, China.

Introduction: Unilateral biportal endoscopy (UBE) is a relatively new yet common minimally invasive procedure in spine surgery, capable of achieving adequate decompression for lumbar spinal stenosis through unilateral laminectomy bilateral decompression (ULBD). Neither additional fusion nor rigid fixation is required, as UBE-ULBD rarely causes iatrogenic lumbar instability. However, to our knowledge, five-level ULBD two-stage UBE without lumbar fusion has been yet to be reported in the treatment of multilevel lumbar spinal stenosis.

Case Description: We present a case of an 80-year-old female patient who developed progressive paralysis of the lower extremities. Radiographic examinations showed multilevel degenerative lumbar spinal stenosis and extensive compression of the dural sac and nerve roots from L1-2 to L5-S1. The patient underwent five-level ULBD through two-stage UBE without lumbar fusion or fixation. One week after the final procedure, the patient could ambulate with walking aids and braces. Moreover, no back pain or limited lumbar motion was observed at the 6-month follow-up.

Conclusion: Multilevel ULBD through UBE may provide elderly patients with an alternative, minimally invasive procedure for treating spinal stenosis. This procedure could be achieved by staging surgeries. In this case, we reported complaints of little back pain, despite not needing to perform lumbar fusion or fixation.
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http://dx.doi.org/10.3389/fsurg.2022.944509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294320PMC
July 2022

Polarized Cu-Bi Site Pairs for Non-Covalent to Covalent Interaction Tuning toward N Photoreduction.

Adv Mater 2022 Jul 21:e2204959. Epub 2022 Jul 21.

School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore.

A universal atomic layer confined doping strategy is developed to prepare Bi O Br materials incorporating isolated Cu atoms. The local polarization can be created along the CuOBi atomic interface, which enables better electron delocalization for effective N activation. The optimized Cu-Bi O Br atomic layers show 5.3× and 88.2× improved photocatalytic nitrogen fixation activity than Bi O Br atomic layer and bulk Bi O Br , respectively, with the NH generation rate reaching 291.1 µmol g h in pure water. The polarized Cu-Bi site pairs can increase the non-covalent interaction between the catalyst's surface and N molecules, then further weaken the covalent bond order in NN. As a result, the hydrogenation pathways can be altered from the associative distal pathway for Bi O Br to the alternating pathway for Cu-Bi O Br . This strategy provides an accessible pathway for designing polarized metal site pairs or tuning the non-covalent interaction and covalent bond order.
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http://dx.doi.org/10.1002/adma.202204959DOI Listing
July 2022

Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With EGFR-Sensitizing Variants Assessed by Circulating Tumor DNA Testing: A Phase 2 Nonrandomized Clinical Trial.

JAMA Oncol 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice.

Objective: To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (EGFR)-sensitizing variants assessed by circulating tumor DNA (ctDNA).

Design, Setting, And Participants: The Efficiency of Icotinib in Plasma ctDNA EGFR Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma EGFR-sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA EGFR variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with EGFR variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021.

Interventions: Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent.

Main Outcomes And Measures: The primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms.

Results: Of 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable.

Conclusions And Relevance: This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based EGFR genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration.

Trial Registration: ClinicalTrials.gov Identifier: NCT03346811.
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http://dx.doi.org/10.1001/jamaoncol.2022.2719DOI Listing
July 2022

Innovation in crisis: The role of 'exaptive relations' for medical device development in response to COVID-19.

Technol Forecast Soc Change 2022 Sep 13;182:121863. Epub 2022 Jul 13.

Cranfield University, College Road, Cranfield, Bedford MK43 0AL, UK.

The COVID-19 pandemic has resulted in huge disruption to the healthcare sector. In response to this, there have been collaborative efforts between many different public and private organizations to foster medical innovations. The effect of crisis upon innovation, particularly medical innovation, remains a debatable subject. In addition, the role of inter-personal relations is becoming more widely acknowledged as a critical feature of innovation. Drawing upon exaptation literature, the study aims to understand the nature of the micro-relations within medical innovations that are undertaken in response to COVID-19. The findings of this paper contribute to the limited literature that examines the performance of medical innovation in response to crisis. In addition to confirming the importance of exaptive pools, exaptive events, and exaptive forums in fostering serendipitous developments, the study makes a contribution to theory by identifying a further form of serendipitous encounter that is 'exaptive relations'.
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http://dx.doi.org/10.1016/j.techfore.2022.121863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276712PMC
September 2022

Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling.

Int J Biol Sci 2022 27;18(10):4219-4232. Epub 2022 Jun 27.

Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Dysbiotic gut microbiota (GM) and NLRP3 inflammasome are proarrhythmic factors in atrial fibrillation (AF). Herein, whether short-chain fatty acid (SCFA) produced from GM fermentation of dietary fiber serving as invisible mediators is yet unclear. Thus, the current study aimed to determine whether SCFA alleviated from NLRP3 signaling-mediated atrial remodeling protects AF development. First, a cross-sectional study based on the GC-MS metabolomics was performed to explore the association between fecal SCFA levels and AF traits in a cohort consisted of 48 individuals. Then, a well-established mice model fed diet deficient or enriched in dietary fiber was established to elucidate the pathophysiological role of SCFA involved in AF susceptibility, atrial remodeling, and G-protein-coupled receptor 43 (GPR43)/NLRP3 signaling. Finally, the effects of SCFA were verified on HL-1 cells. Fecal SCFA levels were remarkably reduced in AF patients with a declining trend from paroxysmal to persistent AF. Prolonged P wave duration based on surface ECG and increased left atrial diameter gained from echocardiography was identified in low-fiber diet mice but lost in SCFA-supplemented group. Lack of dietary fiber enhanced susceptibility to AF under burst pacing, whereas SCFA might exert a protective effect. The supplementation of SCFA prevented dietary fiber deficiency-upregulated phosphorylation of calmodulin-dependent protein kinase II and ryanodine receptor 2, the disarray fibrosis, collagen expression, and NLRP3 inflammasome activation in atrial tissue. Finally, the AF protective roles of SCFA were identified through GPR43 mediated deactivation of NLRP3 by GPR43 knockdown in HL-1 cells. SCFA derived from dietary fiber fermentation by gut commensals alleviates AF development via GPR43/NLRP3 signaling.
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http://dx.doi.org/10.7150/ijbs.70644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274492PMC
July 2022

Signal-on fluorescent sensing strategy for Pb detection based on 8-17 DNAzyme-mediated molecular beacon-type catalytic hairpin assembly circuit.

Anal Bioanal Chem 2022 Jul 13. Epub 2022 Jul 13.

Department of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, 130062, China.

Based on a Pb-specific 8-17 DNAzyme-induced catalytic hairpin assembly (CHA), a simple signal-on fluorescence strategy for lead ion detection was established. 8-17 DNAzyme was used as the recognition element of Pb, which catalyzed the cleavage of the RNA base embedded in the DNA substrate strand, while releasing part of the substrate strand (S') as CHA initiator. And two hairpin probes (H1 and H2-FQ) were designed according to the sequence of S' for CHA, in which H2-FQ was labeled with the fluorophore FAM and quencher BHQ-1 as fluorescent "molecular switch" based on fluorescence resonance energy transfer (FRET). In the presence of Pb, the CHA reaction was triggered to form a large number of H1-H2 complexes, enabling enzyme-free isothermal amplification and a signal-on fluorescence strategy. In the concentration range of 0.5-1000 nM, the fluorescence signal increases with the increase of Pb concentration. The quantitative detection limit of Pb by this method is 0.5 nM, which has better detection performance compared with the FQ-labeled 8-17 DNAzyme method. The established biosensor exhibits good specificity and can be effectively used for the detection of Pb in real samples of river water and grass carp. Through ingenious nucleic acid sequence design, DNAzyme and CHA reactions are integrated to realize the enzyme-free isothermal amplifications and sensitive detection of Pb, which holds potential versatility in food supervision and environmental monitoring.
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http://dx.doi.org/10.1007/s00216-022-04218-wDOI Listing
July 2022

CCAAT/Enhancer-binding Protein Homologous Protein Promotes ROS-mediated Liver Ischemia and Reperfusion Injury by Inhibiting Mitophagy in Hepatocytes.

Transplantation 2022 Jul 13. Epub 2022 Jul 13.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.

Background: Liver ischemia and reperfusion (IR) injury represent a major risk factor in both partial hepatectomy and liver transplantation. CCAAT/enhancer-binding protein homologous protein (CHOP) is a key regulator of cell death, its precise molecular basis in regulating hepatocyte death during liver IR has not been delineated.

Methods: Hepatocellular CHOP deficient mice were generated by bone marrow chimera models using global CHOP knockout mice. Liver partial warm ischemia model and hypoxia/reoxygenation model of primary hepatocytes were applied. Liver injury and mitophagy-related signaling pathways were investigated. IR-stressed patient liver tissues and serum samples were analyzed as well.

Results: Mice with hepatocellular CHOP deficiency exhibited alleviated cell death, decreased reactive oxygen species (ROS) expression, and enhanced mitophagy in hepatocytes after IR, confirmed by in vitro studies of hepatocytes after hypoxia/reoxygenation. Mitochondria ROS scavenge by Mito TEMPO effectively attenuated hepatocyte death and liver IR injury of wild-type mice, whereas no significant effects were observed in hepatocellular CHOP -deficient mice. CHOP depletion upregulated dynamin-related protein 1 and Beclin-1 activation in the mitochondria of hepatocytes leading to enhanced mitophagy. Following IR, increased CHOP expression and impaired mitophagy activation were observed in the livers of patients undergoing hepatectomy. N-acetyl cysteine pretreatment significantly improved the liver function of patients after surgery.

Conclusions: IR-induced CHOP activation exacerbates ROS-mediated hepatocyte death by inhibiting dynamin-related protein 1-Beclin-1-dependent mitophagy.
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http://dx.doi.org/10.1097/TP.0000000000004244DOI Listing
July 2022

An ORFeome of rice E3 ubiquitin ligases for global analysis of the ubiquitination interactome.

Genome Biol 2022 07 11;23(1):154. Epub 2022 Jul 11.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Background: Ubiquitination is essential for many cellular processes in eukaryotes, including 26S proteasome-dependent protein degradation, cell cycle progression, transcriptional regulation, and signal transduction. Although numerous ubiquitinated proteins have been empirically identified, their cognate ubiquitin E3 ligases remain largely unknown.

Results: Here, we generate a complete ubiquitin E3 ligase-encoding open reading frames (UbE3-ORFeome) library containing 98.94% of the 1515 E3 ligase genes in the rice (Oryza sativa L.) genome. In the test screens with four known ubiquitinated proteins, we identify both known and new E3s. The interaction and degradation between several E3s and their substrates are confirmed in vitro and in vivo. In addition, we identify the F-box E3 ligase OsFBK16 as a hub-interacting protein of the phenylalanine ammonia lyase family OsPAL1-OsPAL7. We demonstrate that OsFBK16 promotes the degradation of OsPAL1, OsPAL5, and OsPAL6. Remarkably, we find that overexpression of OsPAL1 or OsPAL6 as well as loss-of-function of OsFBK16 in rice displayed enhanced blast resistance, indicating that OsFBK16 degrades OsPALs to negatively regulate rice immunity.

Conclusions: The rice UbE3-ORFeome is the first complete E3 ligase library in plants and represents a powerful proteomic resource for rapid identification of the cognate E3 ligases of ubiquitinated proteins and establishment of functional E3-substrate interactome in plants.
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http://dx.doi.org/10.1186/s13059-022-02717-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277809PMC
July 2022

Targeting T cells in human diseases and vaccination: rationale and practice.

Nat Immunol 2022 Aug 11;23(8):1157-1168. Epub 2022 Jul 11.

Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, China.

The identification of CD4 T cells localizing to B cell follicles has revolutionized the knowledge of how humoral immunity is generated. Follicular helper T (T) cells support germinal center (GC) formation and regulate clonal selection and differentiation of memory and antibody-secreting B cells, thus controlling antibody affinity maturation and memory. T cells are essential in sustaining protective antibody responses necessary for pathogen clearance in infection and vaccine-mediated protection. Conversely, aberrant and excessive T cell responses mediate and sustain pathogenic antibodies to autoantigens, alloantigens, and allergens, facilitate lymphomagenesis, and even harbor viral reservoirs. T cell generation and function are determined by T cell antigen receptor (TCR), costimulation, and cytokine signals, together with specific metabolic and survival mechanisms. Such regulation is crucial to understanding disease pathogenesis and informing the development of emerging therapies for disease or novel approaches to boost vaccine efficacy.
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http://dx.doi.org/10.1038/s41590-022-01253-8DOI Listing
August 2022

Epigenetics in Alzheimer's Disease.

Front Aging Neurosci 2022 23;14:911635. Epub 2022 Jun 23.

Guangxi Key Lab of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, China.

Alzheimer's disease (AD) is a neurodegenerative disease with unknown pathogenesis and complex pathological manifestations. At present, a large number of studies on targeted drugs for the typical pathological phenomenon of AD (Aβ) have ended in failure. Although there are some drugs on the market that indirectly act on AD, their efficacy is very low and the side effects are substantial, so there is an urgent need to develop a new strategy for the treatment of AD. An increasing number of studies have confirmed epigenetic changes in AD. Although it is not clear whether these epigenetic changes are the cause or result of AD, they provide a new avenue of treatment for medical researchers worldwide. This article summarizes various epigenetic changes in AD, including DNA methylation, histone modification and miRNA, and concludes that epigenetics has great potential as a new target for the treatment of AD.
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http://dx.doi.org/10.3389/fnagi.2022.911635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260511PMC
June 2022

Particle size-resolved emission characteristics of complex polycyclic aromatic hydrocarbon (PAH) mixtures from various combustion sources.

Environ Res 2022 Jul 7;214(Pt 1):113840. Epub 2022 Jul 7.

School of Environment, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety, South China Normal University, Guangzhou, 510006, China. Electronic address:

Combustion of domestic solid fuels is a significant source of polycyclic aromatic hydrocarbons (PAHs). Some oxygenated PAHs (o-PAHs) and PAHs with molecular weight of 302 (MW302 PAHs) are more toxic than the traditional 16 priority PAHs, whereas their emissions were much less elucidated. This study characterized the size-dependent emissions of parent PAHs (p-PAHs), o-PAHs, and MW302 PAHs from various combustion sources. The estimated emission factors (eEFs) from biomass burning sources were highest for most of the PAHs (391-8928 μg/kg), much higher than that of anthracite coal combustion (43.0-145 μg/kg), both which were operated in an indoor stove. Cigarette smoking had a high eEF of o-PAHs (240 ng/g). MW302 PAHs were not found in the emissions of smoking, cooking, and vehicular exhausts. Particle-size distributions of PAHs were compound- and source-dependent, and the tendency to associate with smaller particles was observed especially in biomass burning and cigarette smoking sources. Furthermore, the inter-source differences in PAH eEFs were associated with their dominance in fine particles. PAH composition profiles also varied with the particle size, showing increasing contributions of large-molecule PAHs with decreasing sizes in most cases. The size distributions of p-PAHs are much more significantly dependent on their n-octanol/air partition coefficients and vapor pressures than those of o-PAHs, suggesting differences in mechanisms governing their distributions. Several molecular diagnostic ratios (MDRs), including two based on MW302 PAHs, specific to these combustion scenarios were identified. However, the MDRs within some sources are also strongly size-dependent, providing a new explanation for the uncertainty in their application for source identification of PAHs. This work also highlights the necessity for understanding the size-resolved atmospheric behaviors and fate of PAHs after their emission.
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http://dx.doi.org/10.1016/j.envres.2022.113840DOI Listing
July 2022

CDK5 Mediates Proinflammatory Effects of Microglia through Activated DRP1 Phosphorylation in Rat Model of Intracerebral Hemorrhage.

Dis Markers 2022 27;2022:1919064. Epub 2022 Jun 27.

Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

Introduction: Cyclin-dependent kinase-5 (CDK5) is a key kinase involved in brain development and function and recently found to be involved in neuronal and astroglial apoptosis, neural stem/progenitor cell stemness, mitochondrial fission, and synaptic transmission. But the specific mechanism of CDK5-mediated anti-inflammatory remains unclear in ICH. The aim of the present study was to explore the role of CDK5 in mediating microglia activity through activated DRP1 phosphorylation in a rat ICH model.

Methods: We measured behavioral change after ICH; detected the expression of CDK5 in the rat brain using immunohistochemistry; and measured the protein levels of CDK5, p35, p25, p-histone H1, and p-DRP1 using Western blot analysis. Coimmunoprecipitation analysis indicated interaction of CDK5 and DRP1. Tumor necrosis factor-, interleukin- (IL-) 1, and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA).

Results: After ICH, CDK5 protein level and kinase activity increased. Western blot data showed that CDK5 expression increased from 6 h and peaked at 2 d after ICH ( < 0.05), and the expression of p35 was lowest at 12 h, while the expression of p25 peaked at 2 d after ICH. Besides, p-DRP1 expression change follows with CDK5 kinase activity change. Coimmunoprecipitation showed that interaction between CDK5 and DRP1 certainly exists in microglia. Then, knockdown CDK5 or p35 expression by siRNA reduced the expression level of p-DRP1. ELISA data showed that the protein levels of proinflammatory mediators, such as TNF-, IL-1, and IL-6, were decreased by knockdown of CDK5.

Conclusion: CDK5 may regulate DRP1 by direct phosphorylation in microglia and further induce microglia secreting proinflammation factor.
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http://dx.doi.org/10.1155/2022/1919064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252704PMC
July 2022

Rice catalase OsCATC is degraded by E3 ligase APIP6 to negatively regulate immunity.

Plant Physiol 2022 Jul 4. Epub 2022 Jul 4.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

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http://dx.doi.org/10.1093/plphys/kiac317DOI Listing
July 2022

Timing of live attenuated vaccination in infants exposed to infliximab or adalimumab in utero: A prospective cohort study in 107 children.

J Crohns Colitis 2022 Jul 2. Epub 2022 Jul 2.

Department of Gastroenterology, St Vincent's Hospital, and University of Melbourne, Melbourne, Australia.

Background And Aims: For infants exposed in utero to anti-tumour necrosis factor-a (TNF) medications, it is advised that live-attenuated vaccinations be postponed until drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy.

Methods: We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011-2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood-sample during the first year of life were included.

Results: Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed and 77 from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% (n=25) of infants at 6 months. At 12 months, adalimumab was not detected but 4% (n=3) had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: h ttps ://xiaozhu.shinyapps.io/antiTNFcalculator2/.

Conclusions: Almost one quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. In order to limit the time to live-attenuattated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a 2 nd sample ≥1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.
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http://dx.doi.org/10.1093/ecco-jcc/jjac093DOI Listing
July 2022

Safety of Quinolones in Children: A Systematic Review and Meta-Analysis.

Paediatr Drugs 2022 Jun 30. Epub 2022 Jun 30.

Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.

Background: The results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial.

Objective: The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making.

Data Sources: The MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021.

Study Selection: All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies.

Data Extraction: Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form.

Results: The overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82-2.26; p < 0.001; I = 18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2-6 months: RR 2.56, 95% CI 2.26-2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98-1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37-3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00-1.77; low-quality evidence).

Conclusions: Although the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.
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http://dx.doi.org/10.1007/s40272-022-00513-2DOI Listing
June 2022
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