Publications by authors named "Hao Ding"

392 Publications

Fat reducing effects of leaf extract in overweight patients.

Nat Prod Res 2021 Dec 2:1-6. Epub 2021 Dec 2.

College of Food Sciences and Technology, Shanghai Ocean University, Shanghai, China.

The leaf of (Family Nelumbonaceae) has been widely included in the diet of Chinese people from the time of the Min Dynasty. In this study, a randomized double-blind trial (n = 60) was performed to determine the effects of extract from sun dried leaves (NnEx), which included quercetin-3-glucuronide (Q3GA) as the main components, in overweight patients (24 kg/m
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http://dx.doi.org/10.1080/14786419.2021.2010196DOI Listing
December 2021

Integrated Analysis Reveals a lncRNA-miRNA-mRNA Network Associated with Pigeon Skeletal Muscle Development.

Genes (Basel) 2021 Nov 11;12(11). Epub 2021 Nov 11.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

Growing evidence has demonstrated the emerging role of long non-coding RNA as competitive endogenous RNA (ceRNA) in regulating skeletal muscle development. However, the mechanism of ceRNA regulated by lncRNA in pigeon skeletal muscle development remains unclear. To reveal the function and regulatory mechanisms of lncRNA, we first analyzed the expression profiles of lncRNA, microRNA (miRNA), and mRNA during the development of pigeon skeletal muscle using high-throughput sequencing. We then constructed a lncRNA-miRNA-mRNA ceRNA network based on differentially expressed (DE) lncRNAs, miRNAs, and mRNAs according to the ceRNA hypothesis. Functional enrichment and short time-series expression miner (STEM) analysis were performed to explore the function of the ceRNA network. Hub lncRNA-miRNA-mRNA interactions were identified by connectivity degree and validated using dual-luciferase activity assay. The results showed that a total of 1625 DE lncRNAs, 11,311 DE mRNAs, and 573 DE miRNAs were identified. A ceRNA network containing 9120 lncRNA-miRNA-mRNA interactions was constructed. STEM analysis indicated that the function of the lncRNA-associated ceRNA network might be developmental specific. Functional enrichment analysis identified potential pathways regulating pigeon skeletal muscle development, such as cell cycle and MAPK signaling. Based on the connectivity degree, lncRNAs , , , , and were identified as hub genes in the ceRNA network. lncRNA might regulate the FSHD region gene 1 ()/ SRC proto-oncogene, non-receptor tyrosine kinase () by sponge adsorption of cli-miR-1a-3p to affect the development of pigeon skeletal muscle. Our findings provide a data basis for in-depth elucidation of the lncRNA-associated ceRNA mechanism underlying pigeon skeletal muscle development.
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http://dx.doi.org/10.3390/genes12111787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625974PMC
November 2021

Bioactive cytochalasans from the fungus Arthrinium arundinis DJ-13.

Phytochemistry 2021 Nov 23;194:113009. Epub 2021 Nov 23.

Functional Molecules Analysis and Biotransformation Key Laboratory of Universities in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People's Republic of China. Electronic address:

The investigation of the metabolites from Arthrinium arundinis DJ-13 grown in solid medium revealed six undescribed cytochalasans, arundisins A-F and twelve known compounds. Their structures were initially investigated in detail by spectroscopic analyses and were further confirmed by X-crystallography and ECD experiments. In the in vitro bioassays, arundisins A and B showed cytotoxic activity against the MCF-7 breast cancer cell line with IC values of 18.82 ± 0.36 and 15.20 ± 0.42 μM, respectively. Arundisin F exhibited potent antibacterial activity against Escherichia coli with MIC of 8.00 μg/mL (kanamycin, 2.00 μg/mL), and arundisin D displayed gently antibacterial activity against Candida albicans with MIC of 32.00 μg/mL (Nystatin, 1.00 μg/mL).
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http://dx.doi.org/10.1016/j.phytochem.2021.113009DOI Listing
November 2021

Population Pharmacokinetics and Exposure-Response Analyses for Venetoclax in Combination with R-CHOP in Relapsed/Refractory and Previously Untreated Patients with Diffuse Large B Cell Lymphoma.

Adv Ther 2021 Nov 25. Epub 2021 Nov 25.

Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.

Introduction: Outcomes remain poor in patients with diffuse large B cell lymphoma (DLBCL) who overexpress BCL-2 protein. We present population pharmacokinetics (PopPK) and exposure-response (ER) analyses for venetoclax (a selective BCL-2 inhibitor) administered with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed/refractory (R/R) and previously untreated (1L) non-Hodgkin lymphoma (NHL) from the phase 1b/2 CAVALLI study, to confirm dose selection for future studies.

Methods: Analyses included 216 patients with R/R or 1L NHL treated for eight 21-day cycles with 400-800 mg venetoclax (cycle 1: days 4-10; cycles 2-8: days 1-10) in combination with R for eight cycles and CHOP for 6-8 cycles. A legacy PopPK model for venetoclax was used to describe the observed data and provide post hoc PK parameters. Venetoclax steady-state exposure (AUC) was used to predict clinical efficacy, safety, or tolerability. To isolate the effect of venetoclax, ER analyses referenced data from the R-CHOP arm of a historical control study, GOYA, in 1L DLBCL.

Results: There was no significant association between venetoclax AUC and progression-free survival or complete response either for all-comers or the BCL-2-immunohistochemistry-positive subpopulation. No statistically significant trends were observed with venetoclax AUC and the key grade ≥ 3 adverse events and serious adverse events. Similar dose intensities were observed for venetoclax and R-CHOP components across venetoclax exposures, suggesting venetoclax did not impact delivery of the R-CHOP backbone.

Conclusions: The PopPK and ER analyses, in addition to the positive benefit-risk observed in the clinical data, support the selection of 800 mg venetoclax given with R-CHOP for future studies in BCL-2-immunohistochemistry-positive patients with 1L DLBCL.

Trial Registration: ClinicalTrials.gov Identifier NCT02055820.
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http://dx.doi.org/10.1007/s12325-021-01919-zDOI Listing
November 2021

GELAD chemotherapy with sandwiched radiotherapy for patients with newly diagnosed stage IE/IIE natural killer/T-cell lymphoma: a prospective multicentre study.

Br J Haematol 2021 Nov 21. Epub 2021 Nov 21.

Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Early-stage natural killer/T-cell lymphoma (NK/TCL) patients usually receive a combination of chemotherapy and radiotherapy, but the optimal treatment approach has not yet been established. This study aimed to investigate the efficacy and safety profile of a novel chemotherapy regimen and sandwiched radiotherapy in early-stage NK/TCL. Patients with newly diagnosed stage IE/IIE disease were eligible. Patients were initially treated with two courses of the GELAD regimen (gemcitabine 1·0 g/m day 1, etoposide 60 mg/m days 1-3, pegaspargase 2000 units/m day 4, and dexamethasone 40 mg days 1-4), followed by intensity-modulated radiotherapy (IMRT; 50-56 Gy in 25-28 fractions) and two additional courses of GELAD chemotherapy. A total of 52 patients were enrolled. The overall response rate and complete response rate per Lugano 2014 criteria were 94·2% and 92·3% respectively. With a median follow-up of 32 months, the estimated four-year overall survival rate and progression-free survival rate were 94·2% [95% confidence interval (CI), 83·2% to 93·1%] and 90·4% (95% CI, 78·4% to 95·9%) respectively. The most common adverse events were related to pegaspargase. Haematological toxicities were mild, with grade 3/4 neutropenia in 15·4% of patients. Our study provides a new approach with high activity and improved safety for the treatment of early-stage NK/TCL patients. This study was registered at www.clinicaltrials.gov as NCT02733458.
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http://dx.doi.org/10.1111/bjh.17960DOI Listing
November 2021

Intraspecific and interspecific quorum sensing of bacterial community affects the fate of antibiotic resistance genes during chicken manure composting under penicillin G stress.

Bioresour Technol 2021 Nov 18:126372. Epub 2021 Nov 18.

Key Laboratory of Microbiology, College of Life Sciences, Heilongjiang University, Harbin 150080, China; Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education, Heilongjiang University, Harbin 150500, China. Electronic address:

In this study, the effects of penicillin G (PENG) on the fate of bacterial communities and β-lactamase antibiotic resistance genes (ARGs) during chicken manure composting were assessed, to illustrate the roles of PENG in ARGs behavior. The results showed that the total absolute abundances of 9 ARGs and 4 mobile genetic elements (MGEs) was significantly increased by PENG (P < 0.05). Dozens of potential hosts for ARGs were predominantly affiliated with Firmicutes, Proteobacteria, and Actinobacteria. Meanwhile, the higher concentration of PENG significantly increased the abundance of luxI and luxS in quorum sensing (QS) (P < 0.05), which enhanced the frequency of inter/intraspecific gene "communication." Redundancy analysis and structural equation modeling further revealed that QS had a strong regulatory role in horizontal gene transfer of ARGs mediated via MGEs. These results provide new insight into the mechanism of ARGs propagation in aerobic composting modified by PENG.
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http://dx.doi.org/10.1016/j.biortech.2021.126372DOI Listing
November 2021

ZNF382 controls mouse neuropathic pain via silencer-based epigenetic inhibition of Cxcl13 in DRG neurons.

J Exp Med 2021 Dec 11;218(12). Epub 2021 Nov 11.

Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Nerve injury-induced changes of gene expression in dorsal root ganglion (DRG) are critical for neuropathic pain genesis. However, how these changes occur remains elusive. Here we report the down-regulation of zinc finger protein 382 (ZNF382) in injured DRG neurons after nerve injury. Rescuing this down-regulation attenuates nociceptive hypersensitivity. Conversely, mimicking this down-regulation produces neuropathic pain symptoms, which are alleviated by C-X-C motif chemokine 13 (CXCL13) knockdown or its receptor CXCR5 knockout. Mechanistically, an identified cis-acting silencer at distal upstream of the Cxcl13 promoter suppresses Cxcl13 transcription via binding to ZNF382. Blocking this binding or genetically deleting this silencer abolishes the ZNF382 suppression on Cxcl13 transcription and impairs ZNF382-induced antinociception. Moreover, ZNF382 down-regulation disrupts the repressive epigenetic complex containing histone deacetylase 1 and SET domain bifurcated 1 at the silencer-promoter loop, resulting in Cxcl13 transcriptional activation. Thus, ZNF382 down-regulation is required for neuropathic pain likely through silencer-based epigenetic disinhibition of CXCL13, a key neuropathic pain player, in DRG neurons.
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http://dx.doi.org/10.1084/jem.20210920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590274PMC
December 2021

Anterior Cervical Discectomy and Fusion Combined with Foraminotomy Assisted by High-Definition 3-Dimensional Exoscope in the Treatment of Cervical Spondylotic Radiculopathy Secondary to Bony Foraminal Stenosis.

Orthop Surg 2021 Nov 8. Epub 2021 Nov 8.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

Objective: To evaluate the outcomes of cervical spondylotic radiculopathy secondary to bony foraminal stenosis treated with anterior cervical discectomy and fusion (ACDF) combined with anterior cervical foraminotomy (ACF) assisted by High-Definition 3-Dimensional Exoscope.

Methods: In this retrospective study, a total of 19 consecutive patients (12 males and seven females, with an average of 49.2 years, range from 40 to 59 years) with spondylotic radiculopathy caused by bony foraminal stenosis underwent ACDF combined with ACF assisted by High-Definition 3-Dimensional Exoscope in our hospital between January 2019 and December 2019 were included in this study. All patients signed the consent form before the surgery. The patient baseline information such as gender, age, body mass index (BMI), surgery time, blood loss, hospital stay, lesion segment, side, follow-up time and postoperative complications were recorded. The Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) were measured and compared before surgery, 1 months and final follow-up after surgery. The radiographic outcomes were evaluated using the C -C angel, disc height, foraminal height, superior diagonal distance, inferior diagonal distance, and foraminal area.

Results: The involved levels included C -C (six cases), C -C (10 cases), C -C (three cases). The mean duration of the surgery, mean blood loss, mean hospital stay, and mean follow-up were 100 ± 11.10 min, 19.4 ± 7.05 mL, 7.1 ± 0.99 days, and 12.1 ± 2.25 months, respectively. The average preoperative JOA score was 11.9 ± 1.31, then improved to 15.7 ± 0.73 (t = -13.45, P < 0.001) and 16.2 ± 0.74 (t = -14.39, P < 0.001) at 1 month after operation and at last follow-up, respectively. The average preoperative NDI score was 27.3 ± 3.36, then decreased to 5.1 ± 1.79 (t = 20.63, P < 0.001) and 4.5 ± 1.21 (t = 25.53, P < 0.001) 1 month after operation and at last follow-up, respectively. The average preoperative VAS score was 6.7 ± 0.93, then decreased to 2.4 ± 0.69 (t = 15.05, P < 0.001) and 1.9 ± 0.78 (t = 16.40, P < 0.001) 1 month after operation and at last follow-up, respectively. As compared with the condition before surgery, there was a significant improvement in the C -C angel, disc height, foraminal height, and foraminal area (P < 0.05). None of the patients developed postoperative vascular injury, nerve injury, loosening and rupture of the internal fixation, displacement of interbody fusion cage, and pseudarthrosis.

Conclusion: ACDF combined with ACF assisted by High-Definition 3-Dimensional Exoscope is effective and safe for the treatment of CSR caused by secondary to bony foraminal stenosis.
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http://dx.doi.org/10.1111/os.13040DOI Listing
November 2021

Chemical state mapping of simulant Chernobyl lava-like fuel containing material using micro-focused synchrotron X-ray spectroscopy.

J Synchrotron Radiat 2021 Nov 13;28(Pt 6):1672-1683. Epub 2021 Sep 13.

NucleUS Immobilisation Science Laboratory, Department of Materials Science and Engineering, University of Sheffield, Sheffield S1 3JD, United Kingdom.

Uranium speciation and redox behaviour is of critical importance in the nuclear fuel cycle. X-ray absorption near-edge spectroscopy (XANES) is commonly used to probe the oxidation state and speciation of uranium, and other elements, at the macroscopic and microscopic scale, within nuclear materials. Two-dimensional (2D) speciation maps, derived from microfocus X-ray fluorescence and XANES data, provide essential information on the spatial variation and gradients of the oxidation state of redox active elements such as uranium. In the present work, we elaborate and evaluate approaches to the construction of 2D speciation maps, in an effort to maximize sensitivity to the U oxidation state at the U L-edge, applied to a suite of synthetic Chernobyl lava specimens. Our analysis shows that calibration of speciation maps can be improved by determination of the normalized X-ray absorption at excitation energies selected to maximize oxidation state contrast. The maps are calibrated to the normalized absorption of U L XANES spectra of relevant reference compounds, modelled using a combination of arctangent and pseudo-Voigt functions (to represent the photoelectric absorption and multiple-scattering contributions). We validate this approach by microfocus X-ray diffraction and XANES analysis of points of interest, which afford average U oxidation states in excellent agreement with those estimated from the chemical state maps. This simple and easy-to-implement approach is general and transferrable, and will assist in the future analysis of real lava-like fuel-containing materials to understand their environmental degradation, which is a source of radioactive dust production within the Chernobyl shelter.
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http://dx.doi.org/10.1107/S1600577521007748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570221PMC
November 2021

Construction of miRNA-mRNA network in the differentiation of chicken preadipocytes.

Br Poult Sci 2021 Nov 5. Epub 2021 Nov 5.

College of animal Science & Technology, Department of Animal Genetics, Breeding & Reproduction, Yangzhou, China.

1. MicroRNAs (miRNAs) play key roles in regulating lipid metabolism, adipogenesis and fat deposition in chicken. To date, there are only a few miRNAs that had been confirmed to be involved in chicken adipogenesis. The detailed mechanisms by which miRNAs regulate chicken adipogenesis remain largely unknown.

2. To identify candidate miRNAs involved in chicken preadipocyte differentiation and explore potential mechanisms behind their functions, the following study analysed and identified miRNA and mRNA expression levels in undifferentiated and differentiated preadipocytes. Hub miRNA-mRNA interactions were identified, and the degree of connectivity of DE miRNAs in the network was established.

3. A total of 145 DE miRNAs and 660 DE mRNAs were identified between undifferentiated and differentiated preadipocytes. An miRNA-mRNA network was constructed, including 29 DE miRNAs and 155 DE mRNAs, forming 470 miRNA-mRNA interactions. Functional enrichment analysis showed that DE mRNAs in the network were significantly enriched in 712 biological processes and 13 KEGG pathways. Based on the connectivity degree, five DE miRNAs with higher degrees miR-195-x, gga-miR-200a-3p, gga-miR-135a-5p, novel-m0067-5p and novel-m0270-5p were identified as hub miRNAs. Fifty-eight DE mRNAs interacted with these five hub miRNAs and formed 70 miRNA-mRNA interactions.

4. This study constructed a miRNA-mRNA network associated with chicken preadipocyte differentiation and identified five hub miRNAs in the network. The findings identified the number of chicken adipogenic miRNAs and laid the foundation for elucidating the miRNA-mediated regulatory mechanism in chicken adipogenesis.
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http://dx.doi.org/10.1080/00071668.2021.2000585DOI Listing
November 2021

Gd-EOB-DTPA-enhanced magnetic resonance imaging may help identify patients with hepatocellular carcinoma eligible for treatment targeted at RAF1.

Abdom Radiol (NY) 2021 Nov 5. Epub 2021 Nov 5.

Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.

Purpose: The RAF1 expression affects prognosis in patients with hepatocellular carcinoma (HCC) treated with sorafenib. We examined the expression of sorafenib-targeted gene RAF1 to ascertain its relationship with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI) characteristics. We also explored the predictive potential of RAF1 expression markers in the treatment of HCC.

Patients And Methods: Sixty-five patients with HCC who underwent preoperative enhanced MRI scanning were included in this study. We analyzed the qualitative and quantitative characteristics of enhanced MRI findings in patients with HCC. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) analyses were used to detect the protein and mRNA expression levels of RAF1 in HCC. Correlation and logistic regression analyses were used to evaluate the relationship between these image features and the RAF1 gene expression levels in HCC.

Results: The IHC analysis indicated a significant difference in tumor thrombus group (P = 0.037), RT-PCR results revealed a significant between-group difference for both tumor margins (P = 0.033) and capsule (P = 0.04). Binary logistic regression analysis results suggest that independent MRI predictors were regular tumor margins [P = 0.035, odds ratio (OR) = 3.145, 95% confidence interval (CI) 1.087-9.103] and thrombus (P = 0.046, OR = 4.421, 95% CI 1.024-19.08) with high RAF1expression; the tumor capsule was not an independent predictor.

Conclusion: We found a correlation between MRI features and the RAF1 gene expression, Regular tumor margin and the presence of tumor thrombus are indicators of high RAF1 expression in HCC. Enhanced MRI may be useful for identifying patients with HCC eligible for targeted treatment.
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http://dx.doi.org/10.1007/s00261-021-03325-zDOI Listing
November 2021

Ferroptosis Promotes Cyst Growth in Autosomal Dominant Polycystic Kidney Disease Mouse Models.

J Am Soc Nephrol 2021 11;32(11):2759-2776

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota

Background: Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, is regulated by different forms of cell death, including apoptosis and autophagy. However, the role in ADPKD of ferroptosis, a recently discovered form of cell death mediated by iron and lipid metabolism, remains elusive.

Methods: To determine a pathophysiologic role of ferroptosis in ADPKD, we investigated whether the absence of (encoding polycystin-1) affected the expression of key factors involved in the process of ferroptosis, using Western blot and qRT-PCR analysis in mutant renal cells and tissues. We also examined whether treatment with erastin, a ferroptosis inducer, and ferrostain-1, a ferroptosis inhibitor, affected cyst growth in mutant mouse models.

Results: We found that kidney cells and tissues lacking exhibit extensive metabolic abnormalities, including reduced expression of the system Xc amino acid antiporter (critical for import of cystine), of iron exporter (ferroportin), and of GPX4 (a key and negative regulator of ferroptosis). The abnormalities also include increased expression of iron importers (TfR1, DMT1) and HO-1, which in turn result in high iron levels, low GSH and GPX4 activity, increased lipid peroxidation, and propensity to ferroptosis. We further found that erastin increased, and ferrostatin-1 inhibited ferroptotic cell death and proliferation of -deficient cells in kidneys from mutant mice. A lipid peroxidation product increased in -deficient cells, 4HNE, promoted the proliferation of survived mutant cells activation of Akt, S6, Stat3, and Rb during the ferroptotic process, contributing to cyst growth.

Conclusion: These findings indicate that ferroptosis contributes to ADPKD progression and management of ferroptosis may be a novel strategy for ADPKD treatment.
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http://dx.doi.org/10.1681/ASN.2021040460DOI Listing
November 2021

Effects of dietary tributyrin and physterol ester supplementation on growth performance, intestinal morphology, microbiota and metabolites in weaned piglets.

J Appl Microbiol 2021 Oct 27. Epub 2021 Oct 27.

College of Animal Science and Technology, Hunan Agricultural University, Hunan Co-Innovation of Animal Production Safety, Changsha, Hunan, China.

Aim: This study was conducted to investigate the effects of dietary tributyrin (TB) and physterol ester (PSE) supplementation on the growth performance and intestinal health of weaned piglets.

Methods And Results: Ninety-six piglets were randomly allocated to one of four groups, including a control group (basal diet), TB group (basal diet + 1500 g t  TB), PSE group (basal diet + 300 g t PSE) and TB + PSE group (basal diet + 1500 g t  TB + 300 g t PSE). All groups had eight replicates with three piglets per replicate. The experiment lasted for 28 days. The results showed that dietary TB supplementation increased (p < 0.05) average daily feed intake and average daily gain, as well as the acetate and butyrate concentration in ileum, and dietary PSE supplementation decreased (p < 0.05) the ratio of feed to gain (F/G) on days 1-14 of the trial. Dietary TB or PSE alone supplementation improved the ratio of villus height to crypt depth (VH/CD) and the expression level of Occludin in ileum. The linear discriminant analysis effect size analysis identified eight biomarkers in the control group, 18 in the TB + PSE group, two in the PSE group in ileum respectively. Correlation analysis showed that the relative abundances of Enterococcus, and Streptococcus were positively correlated (p < 0.05) with propionate concentration, while the relative abundance of Clostridium_sensu_stricto_1 was negatively correlated (p < 0.05) with acetate concentration in ileum.

Conclusion: These findings suggest that dietary TB or PSE alone supplementation could alter the growth performance, intestinal morphology, microbiota community and metabolites of weaned piglets.

Significance And Impact Of The Study: Weaning stress is a major cause of slow growth and increased diarrhoea in piglets. This study demonstrated that dietary TB and PSE presented a beneficial role in growth performance and gut health via regulating intestinal morphology, microbiota composition and metabolites.
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http://dx.doi.org/10.1111/jam.15321DOI Listing
October 2021

The Long Terminal Repeats of ERV6 Are Activated in Pre-Implantation Embryos of Cynomolgus Monkey.

Cells 2021 10 9;10(10). Epub 2021 Oct 9.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.

Precise gene regulation is critical during embryo development. Long terminal repeat elements (LTRs) of endogenous retroviruses (ERVs) are dynamically expressed in blastocysts of mammalian embryos. However, the expression pattern of LTRs in monkey blastocyst is still unknown. By single-cell RNA-sequencing (seq) data of cynomolgus monkeys, we found that LTRs of several ERV families, including MacERV6, MacERV3, MacERV2, MacERVK1, and MacERVK2, were highly expressed in pre-implantation embryo cells including epiblast (EPI), trophectoderm (TrB), and primitive endoderm (PrE), but were depleted in post-implantation. We knocked down MacERV6-LTR1a in cynomolgus monkeys with a short hairpin RNA (shRNA) strategy to examine the potential function of MacERV6-LTR1a in the early development of monkey embryos. The silence of MacERV6-LTR1a mainly postpones the differentiation of TrB, EPI, and PrE cells in embryos at day 7 compared to control. Moreover, we confirmed MacERV6-LTR1a could recruit Estrogen Related Receptor Beta (ESRRB), which plays an important role in the maintenance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF and Wnt signaling pathways. In summary, these results suggest that MacERV6-LTR1a is involved in gene regulation of the pre-implantation embryo of the cynomolgus monkeys.
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http://dx.doi.org/10.3390/cells10102710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534818PMC
October 2021

Improving Sperm Cryopreservation With Type III Antifreeze Protein: Proteomic Profiling of Cynomolgus Macaque () Sperm.

Front Physiol 2021 4;12:719346. Epub 2021 Oct 4.

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China.

Antifreeze protein III (AFP III) is used for the cryopreservation of germ cells in various animal species. However, the exact mechanism of its cryoprotection is largely unknown at the molecular level. In this study, we investigated the motility, acrosomal integrity, and mitochondrial membrane potential (MMP), as well as proteomic change, of cynomolgus macaque sperm after cryopreservation. Sperm motility, acrosomal integrity, and MMP were lower after cryopreservation ( < 0.001), but significant differences in sperm motility and MMP were observed between the AFP-treated sperm sample (Cryo+AFP) and the non-treated sample (Cryo-AFP) ( < 0.01). A total of 141 and 32 differentially expressed proteins were, respectively, identified in cynomolgus macaque sperm cryopreserved without and with 0.1 μg/ml AFP III compared with fresh sperm. These proteins were mainly involved in the mitochondrial production of reactive oxygen species (ROS), glutathione (GSH) synthesis, and cell apoptosis. The addition of AFP III in the sperm freezing medium resulted in significant stabilization of cellular molecular functions and/or biological processes in sperm, as illustrated by the extent of proteomic changes after freezing and thawing. According to the proteomic change of differentially expressed proteins, we hypothesized a novel molecular mechanism for cryoprotection that AFP III may reduce the release of cytochrome c and thereby reduce sperm apoptosis by modulating the production of ROS in mitochondria. The molecular mechanism that AFP III acts with sperm proteins for cellular protection against cryoinjuries needs further study.
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http://dx.doi.org/10.3389/fphys.2021.719346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521148PMC
October 2021

Characterization and identification of a novel microbial consortium M2 and its effect on fermentation quality and enzymatic hydrolysis of sterile rice straw.

J Appl Microbiol 2021 Oct 18. Epub 2021 Oct 18.

Institute of Ensiling and Processing of Grass, College of Agro-grassland Science, Nanjing Agricultural University, Nanjing, China.

Aims: To isolate and enrich lignocellulolytic microbial consortia from yak (Bos grunniens) rumen and evaluate their effects on the fermentation characteristics and enzymatic hydrolysis in rice straw silage.

Methods And Results: A novel microbial consortium M2 with high CMCase and xylanase activities was enriched and observed to be prone to use natural carbon sources. Its predominant genus was Enterococcus, and most carbohydrate-active enzyme (CAZyme) genes belonged to the glycosyl hydrolases class. The consortium M2 was introduced with or without combined lactic acid bacteria (XA) to rice straw silage for 60 days. Inoculating the consortium M2 notably decreased the structural carbohydrate contents and pH of rice straw silages. Treatment that combines consortium M2 and XA resulted in the highest levels of lactic acid and lignocellulose degradation. The consortium M2 alone or combined with XA significantly (p < 0.01) increased water-soluble carbohydrates (WSCs), mono- and disaccharides contents compared with the XA silage. Combined addition obviously improved the enzymatic conversion efficiency of rice straw silage with higher glucose and xylose yields (23.39 and 12.91 w/w% DM, respectively).

Conclusions: Ensiling pretreatment with the microbial consortium M2 in sterile rice straw improved fermentation characteristics. The combined application of consortium M2 with XA had synergistic effects on promoting the degradation of structural carbohydrates and enzymatic hydrolysis.

Significance And Impact Of The Study: Rice straw is difficult to ensile because of its low WSC and high structural carbohydrate contents. The microbial consortium M2 identified herein exhibits great potential for degrading fibrous substrates, and their combination with XA provides a faster and more effective synergistic strategy for biorefinery of lignocellulosic biomass.
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http://dx.doi.org/10.1111/jam.15328DOI Listing
October 2021

Current Applications and Future Development of Magnetic Resonance Fingerprinting in Diagnosis, Characterization, and Response Monitoring in Cancer.

Cancers (Basel) 2021 Sep 22;13(19). Epub 2021 Sep 22.

High Dimensional Neurology Group, Queen's Square Institute of Neurology, University College London, London WC1N 3BG, UK.

Magnetic resonance imaging (MRI) has enabled non-invasive cancer diagnosis, monitoring, and management in common clinical settings. However, inadequate quantitative analyses in MRI continue to limit its full potential and these often have an impact on clinicians' judgments. Magnetic resonance fingerprinting (MRF) has recently been introduced to acquire multiple quantitative parameters simultaneously in a reasonable timeframe. Initial retrospective studies have demonstrated the feasibility of using MRF for various cancer characterizations. Further trials with larger cohorts are still needed to explore the repeatability and reproducibility of the data acquired by MRF. At the moment, technical difficulties such as undesirable processing time or lack of motion robustness are limiting further implementations of MRF in clinical oncology. This review summarises the latest findings and technology developments for the use of MRF in cancer management and suggests possible future implications of MRF in characterizing tumour heterogeneity and response assessment.
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http://dx.doi.org/10.3390/cancers13194742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507535PMC
September 2021

A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation.

PLoS Genet 2021 10 8;17(10):e1009817. Epub 2021 Oct 8.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

The yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans, which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distinct stimuli: mating stimulation or glucosamine (GlcN), the monomer of cell wall chitosan. However, it remains poorly understood how the signal specificity for Cryptococcus morphological transition by disparate stimuli is ensured. Here, by integrating temporal expression signature analysis and phenome-based clustering evaluation, we demonstrate that GlcN specifically triggers a unique cellular response, which acts as a critical determinant underlying the activation of GlcN-induced filamentation (GIF). This cellular response is defined by an unusually hyperactive cell wall synthesis that is highly ATP-consuming. A novel cell surface protein Gis1 was identified as the indicator molecule for the GlcN-induced cell wall response. The Mpk1-directed cell wall pathway critically bridges global cell wall gene induction and intracellular ATP supply, ensuring the Gis1-dependent cell wall response and the stimulus specificity of GIF. We further reveal that the ability of Mpk1 to coordinate the cell wall response and GIF activation is conserved in different Cryptococcus pathogens. Phosphoproteomics-based profiling together with genetic and phenotypic analysis revealed that the Mpk1 kinase mediates the regulatory specificity of GIF through a coordinated downstream regulatory network centered on Skn7 and Crz1. Overall, our findings discover an unprecedented and conserved cell wall biosynthesis-dependent fungal differentiation commitment mechanism, which enables the signal specificity of pathogenicity-related dimorphism induced by GlcN in Cryptococcus pathogens.
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http://dx.doi.org/10.1371/journal.pgen.1009817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500725PMC
October 2021

Auto-focusing and quantitative phase imaging using deep learning for the incoherent illumination microscopy system.

Opt Express 2021 Aug;29(17):26385-26403

It is well known that the quantitative phase information which is vital in the biomedical study is hard to be directly obtained with bright-field microscopy under incoherent illumination. In addition, it is impossible to maintain the living sample in focus over long-term observation. Therefore, both the autofocusing and quantitative phase imaging techniques have to be solved in microscopy simultaneously. Here, we propose a lightweight deep learning-based framework, which is constructed by residual structure and is constrained by a novel loss function model, to realize both autofocusing and quantitative phase imaging. It outputs the corresponding in-focus amplitude and phase information at high speed (10fps) from a single-shot out-of-focus bright-field image. The training data were captured with a designed system under a hybrid incoherent and coherent illumination system. The experimental results verify that the focused and quantitative phase images of non-biological samples and biological samples can be reconstructed by using the framework. It provides a versatile quantitative technique for continuous monitoring of living cells in long-term and label-free imaging by using a traditional incoherent illumination microscopy system.
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http://dx.doi.org/10.1364/OE.434014DOI Listing
August 2021

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ.

Alcohol Alcohol 2021 Sep 22. Epub 2021 Sep 22.

Rehabilitation Department, Qingdao Mental Health Center, Shandong 266034, PR China.

Aims: Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism.

Methods: The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot.

Results: GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ.

Conclusions: Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.
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http://dx.doi.org/10.1093/alcalc/agab065DOI Listing
September 2021

Sirtuin 3 regulates mitochondrial protein acetylation and metabolism in tubular epithelial cells during renal fibrosis.

Cell Death Dis 2021 09 13;12(9):847. Epub 2021 Sep 13.

Center for Kidney Disease, The second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210003, China.

Proximal tubular epithelial cells (TECs) demand high energy and rely on mitochondrial oxidative phosphorylation as the main energy source. However, this is disturbed in renal fibrosis. Acetylation is an important post-translational modification for mitochondrial metabolism. The mitochondrial protein NAD-dependent deacetylase sirtuin 3 (SIRT3) regulates mitochondrial metabolic function. Therefore, we aimed to identify the changes in the acetylome in tubules from fibrotic kidneys and determine their association with mitochondria. We found that decreased SIRT3 expression was accompanied by increased acetylation in mitochondria that have separated from TECs during the early phase of renal fibrosis. Sirt3 knockout mice were susceptible to hyper-acetylated mitochondrial proteins and to severe renal fibrosis. The activation of SIRT3 by honokiol ameliorated acetylation and prevented renal fibrosis. Analysis of the acetylome in separated tubules using LC-MS/MS showed that most kidney proteins were hyper-acetylated after unilateral ureteral obstruction. The increased acetylated proteins with 26.76% were mitochondrial proteins which were mapped to a broad range of mitochondrial pathways including fatty acid β-oxidation, the tricarboxylic acid cycle (TCA cycle), and oxidative phosphorylation. Pyruvate dehydrogenase E1α (PDHE1α), which is the primary link between glycolysis and the TCA cycle, was hyper-acetylated at lysine 385 in TECs after TGF-β1 stimulation and was regulated by SIRT3. Our findings showed that mitochondrial proteins involved in regulating energy metabolism were acetylated and targeted by SIRT3 in TECs. The deacetylation of PDHE1α by SIRT3 at lysine 385 plays a key role in metabolic reprogramming associated with renal fibrosis.
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http://dx.doi.org/10.1038/s41419-021-04134-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437958PMC
September 2021

A new cycloheptane derivative from the fungus JT-8.

Nat Prod Res 2021 Sep 9:1-9. Epub 2021 Sep 9.

Functional Molecules Analysis and Biotransformation Key Laboratory of Universities in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Kunming, P.R. China.

A new highly oxygenated cycloheptane derivative crustane (), along with fourteen known compounds (-) were isolated from JT-8. The structure of compound was determined by extensive spectroscopic data, DP4+ probability analyses and dimolybdenum CD method. Compound exhibited moderate antibacterial activity against with MIC of 4.0 μg/mL.
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http://dx.doi.org/10.1080/14786419.2021.1949592DOI Listing
September 2021

Epigenetics in kidney diseases.

Adv Clin Chem 2021 21;104:233-297. Epub 2020 Oct 21.

Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States. Electronic address:

Epigenetics examines heritable changes in DNA and its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in kidney cell biology through the action of DNA methylation, chromatin modification via epigenetic regulators and non-coding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis are multistep processes associated with numerous molecular alterations even in individual kidney cells. Epigenetic alterations, including anomalous DNA methylation, aberrant histone alterations and changes of microRNA expression all contribute to kidney pathogenesis. These changes alter the genome-wide epigenetic signatures and disrupt essential pathways that protect renal cells from uncontrolled growth, apoptosis and development of other renal associated syndromes. Molecular changes impact cellular function within kidney cells and its microenvironment to drive and maintain disease phenotype. In this chapter, we briefly summarize epigenetic mechanisms in four kidney diseases including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis. We primarily focus on current knowledge about the genome-wide profiling of DNA methylation and histone modification, and epigenetic regulation on specific gene(s) in the pathophysiology of these diseases and the translational potential of identifying new biomarkers and treatment for prevention and therapy. Incorporating epigenomic testing into clinical research is essential to elucidate novel epigenetic biomarkers and develop precision medicine using emerging therapies.
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http://dx.doi.org/10.1016/bs.acc.2020.09.005DOI Listing
October 2021

Gelation Based on Host-Guest Interactions Induced by Multi-Functionalized Nanosheets.

Gels 2021 Aug 4;7(3). Epub 2021 Aug 4.

Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA.

Host-guest interaction, being reversible and stimuli-responsive, is ideal to be applied to the design of hydrogels. We created a gelation system based on the host-guest interactions between the adamantyl groups and β-cyclodextrin (β-CD) polymer. N,N,N-trimethyl-1-adamantylammonium hydroxide (TriMAA) cations were attached to the pre-exfoliated α-zirconium phosphate (α-ZrP) nanosheets by ionic bonding through a displacement reaction with the exfoliating agents. The exfoliated α-ZrP nanosheets with adamantyl groups directly or indirectly attached to the surface act as reversible high-functionality crosslinkers within the β-CD polymer. The gelation occurred at a host-to-guest ratio of 1:10 or 1:5 at room temperature within minutes. The agents used to exfoliate α-ZrP can tailor the surface of the resultant α-ZrP nanosheets and the ionic strength of the system, which directly affects the further gelation results. Plus, the exfoliating agent cations may generate a host-and-guest interaction with the β-CD polymer as well. This gelation process without covalent bonding formation should help fellow researchers to better understand the gelation system and host-guest interactions.
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http://dx.doi.org/10.3390/gels7030106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396050PMC
August 2021

Transcriptome Analysis of Differentially Expressed mRNA Related to Pigeon Muscle Development.

Animals (Basel) 2021 Aug 5;11(8). Epub 2021 Aug 5.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China.

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA-Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co-expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA-mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS-00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT-PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.
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http://dx.doi.org/10.3390/ani11082311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388485PMC
August 2021

Antibiotic-Induced Dysbiosis of Microbiota Promotes Chicken Lipogenesis by Altering Metabolomics in the Cecum.

Metabolites 2021 Jul 28;11(8). Epub 2021 Jul 28.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

Elucidation of the mechanism of lipogenesis and fat deposition is essential for controlling excessive fat deposition in chicken. Studies have shown that gut microbiota plays an important role in regulating host lipogenesis and lipid metabolism. However, the function of gut microbiota in the lipogenesis of chicken and their relevant mechanisms are poorly understood. In the present study, the gut microbiota of chicken was depleted by oral antibiotics. Changes in cecal microbiota and metabolomics were detected by 16S rRNA sequencing and ultra-high performance liquid chromatography coupled with MS/MS (UHPLC-MS/MS) analysis. The correlation between antibiotic-induced dysbiosis of gut microbiota and metabolites and lipogenesis were analysed. We found that oral antibiotics significantly promoted the lipogenesis of chicken. 16S rRNA sequencing indicated that oral antibiotics significantly reduced the diversity and richness and caused dysbiosis of gut microbiota. Specifically, the abundance of Proteobacteria was increased considerably while the abundances of Bacteroidetes and Firmicutes were significantly decreased. At the genus level, the abundances of genera and were significantly increased while the abundances of 12 genera were significantly decreased, including . UHPLC-MS/MS analysis showed that antibiotic-induced dysbiosis of gut microbiota significantly altered cecal metabolomics and caused declines in abundance of 799 metabolites and increases in abundance of 945 metabolites. Microbiota-metabolite network revealed significant correlations between 4 differential phyla and 244 differential metabolites as well as 15 differential genera and 304 differential metabolites. Three metabolites of l-glutamic acid, pantothenate acid and -acetyl-l-aspartic acid were identified as potential metabolites that link gut microbiota and lipogenesis in chicken. In conclusion, our results showed that antibiotic-induced dysbiosis of gut microbiota promotes lipogenesis of chicken by altering relevant metabolomics. The efforts in this study laid a basis for further study of the mechanisms that gut microbiota regulates lipogenesis and fat deposition of chicken.
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http://dx.doi.org/10.3390/metabo11080487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398106PMC
July 2021

Serum tumor markers for the prediction of concordance between genomic profiles from liquid and tissue biopsy in patients with advanced lung adenocarcinoma.

Transl Lung Cancer Res 2021 Jul;10(7):3236-3250

Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Background: The concordance between mutations detected from plasma and tissue is critical for treatment choices of patients with advanced lung adenocarcinoma.

Methods: We prospectively analyzed the association of the serum tumor markers with the concordance between blood and tissue genomic profiles from 185 patients with advanced lung adenocarcinoma. The concordance was defined according to 3 criteria. Class 1 included all targetable driver mutations in 8 genes; class 2 included class 1 mutations plus mutations in , , and ; class 3 included class 2 mutations plus tumor mutation burden (TMB) status.

Results: Collectively, 150 out of 185 patients had mutations in both tissue and plasma samples, while one patient was mutation-negative for both, resulting a concordance of 81.6%. The concordance rate for class 1 mutations was 80%, and 65% and 69% for class 2 and class 3, respectively. Carbohydrate antigen 19-9 (CA19-9) or cytokeratin 19 (CYFRA21-1) levels higher than the normal upper limit predicted the concordance of tissue and blood results in class 1 (P=0.005, P=0.011), class 2 (P=0.011, P<0.001), and class 3 (P=0.001, P=0.014). In class 1, the cutoff values of CA19-9 were 30, 36, and 284 U/mL to reach the concordance thresholds of 90%, 95%, and 100%, respectively (P=0.032, P=0.003, P=0.043). For CYFRA21-1, the cutoff values were 6, 18, and 52 µg/L (P=0.005, P=0.051, P=0.354). In class 2, the cutoff values for CYFRA21-1 were 18, 22, and 52 µg/L (P=0.001, P=0.001, P=0.052). In class 3, the cutoff values for CA19-9 were 36, 39, and 85 U/mL (P=0.003, P=0.001, P=0.008). For CYFRA21-1, the cutoff values were 22, 52, and 52 µg/L (P=0.900, P>0.99, P>0.99). When the sum score for 4 serum tumor markers was greater than 35, both class 1, class 2, and class 3 reached a predictive threshold of 90%.

Conclusions: Serum tumor markers can be used as easy and practical clinical predictors of concordance in mutation profiles between blood and tissue samples from patients with advanced lung adenocarcinoma.
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http://dx.doi.org/10.21037/tlcr-21-543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350084PMC
July 2021

CPT1α maintains phenotype of tubules via mitochondrial respiration during kidney injury and repair.

Cell Death Dis 2021 08 14;12(8):792. Epub 2021 Aug 14.

Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Impaired energy metabolism in proximal tubular epithelial cells (PTECs) is strongly associated with various kidney diseases. Here, we characterized proximal tubular phenotype alternations during kidney injury and repair in a mouse model of folic acid nephropathy, in parallel, identified carnitine palmitoyltransferase 1α (CPT1α) as an energy stress response accompanied by renal tubular dedifferentiation. Genetic ablation of Cpt1α aggravated the tubular injury and interstitial fibrosis and hampered kidney repair indicate that CPT1α is vital for the preservation and recovery of tubular phenotype. Our data showed that the lipid accumulation and mitochondrial mass reduction induced by folic acid were persistent and became progressively more severe in PTECs without CPT1α. Interference of CPT1α reduced capacities of mitochondrial respiration and ATP production in PTECs, and further sensitized cells to folic acid-induced phenotypic changes. On the contrary, overexpression of CPT1α protected mitochondrial respiration and prevented against folic acid-induced tubular cell damage. These findings link CPT1α to intrinsic mechanisms regulating the mitochondrial respiration and phenotype of kidney tubules that may contribute to renal pathology during injury and repair.
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http://dx.doi.org/10.1038/s41419-021-04085-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364553PMC
August 2021

Toward future adaptive deep brain stimulation for Parkinson's disease: the novel biomarker - narrowband gamma oscillation.

Neural Regen Res 2022 Mar;17(3):557-558

Movement Disorders and Neurostimulation, Biomedical Statistics and Multimodal Signal Processing, Department of Neurology, Johannes Gutenberg University, Mainz, Germany.

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http://dx.doi.org/10.4103/1673-5374.320984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504379PMC
March 2022

Catalyst-free arylation of sulfonamides visible light-mediated deamination.

Chem Sci 2021 Jul 5;12(27):9556-9560. Epub 2021 Jun 5.

Key Laboratory of Functional Small Organic Molecules, Ministry of Education, Jiangxi Normal University Nanchang 330022 China

A novel arylation of sulfonamides with boronic acids to afford numerous diaryl sulfones a visible light-mediated N-S bond cleavage other than the typical transition-metal-catalyzed C(O)-N bond activation is described. This methodology, which represents the first catalyst-free protocol for the sulfonylation of boronic acids, is characterized by its simple reaction conditions, good functional group tolerance and high efficiency. Several successful examples for the late-stage functionalization of diverse sulfonamides indicate the high potential utility of this method in pharmaceutical science and organic synthesis.
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http://dx.doi.org/10.1039/d1sc02266kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279011PMC
July 2021
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