Publications by authors named "Bo Zhang"

4,687 Publications

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Clinical value of tumor-associated antigens and autoantibody panel combination detection in the early diagnostic of lung cancer.

Cancer Biomark 2021 Jun 19. Epub 2021 Jun 19.

Background: This study aimed to investigate the efficiency of combining tumor-associated antigens (TAAs) and autoantibodies in the diagnosis of lung cancer.

Methods: The serum levels of TAAs and seven autoantibodies (7-AABs) were detected from patients with lung cancer, benign lung disease and healthy controls. The performance of a new panel by combing TAAs and 7-AABs was evaluated for the early diagnosis of lung cancer.

Results: The positive rate of 7-AABs was higher than the single detection of antibody. The positive rate of the combined detection of 7-AABs in lung cancer group (30.2%) was significantly higher than that of healthy controls (16.8%), but had no statistical difference compared with that of benign lung disease group (20.8%). The positive rate of 7-AABs showed a tendency to increase in lung cancer patients with higher tumor-node-metastasis (TNM) stages. For the pathological subtype analysis, the positive rate of 7-AABs was higher in patients with squamous cell carcinoma and small cell lung cancer than that of adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 211 (CYFRA 211) were significantly higher than that of benign lung disease and healthy control groups. An optimal model was established (including 7-AABs, CEA and CYFRA21-1) to distinguish lung cancer from control groups. The performance of this model was superior than that of single markers, with a sensitivity of 52.26% and specificity of 77.46% in the training group. Further assessment was studied in another validation group, with a sensitivity of 44.02% and specificity of 83%.

Conclusions: The diagnostic performance was enhanced by combining 7-AABs, CEA and CYFRA21-1, which has critical value for the screening and early detection of lung cancer.
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http://dx.doi.org/10.3233/CBM-210099DOI Listing
June 2021

Uncommon carbene-to-azole ligand rearrangement of N-heterocyclic carbenes in a ruthenium system.

Chem Commun (Camb) 2021 Jun 21. Epub 2021 Jun 21.

Department of Chemistry, Capital Normal University, Beijing, P. R. China.

The study of non-innocent behavior of NHCs (NHCs = N-heterocyclic carbenes) has great implications for NHC-involved catalysis. Herein, we report a new type of NHC-to-azole rearrangement, during which process the carbene backbone and the substituent are both non-innocent. To the best of our knowledge, this work also presents the first example of NHC-to-azole rearrangements for aryl-substituted NHCs.
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http://dx.doi.org/10.1039/d1cc01871jDOI Listing
June 2021

Cistanoside of ameliorates hypoxia-induced male reproductive damage via suppression of oxidative stress.

Am J Transl Res 2021 15;13(5):4342-4359. Epub 2021 May 15.

Department of Urology, Tang Du Hospital, The Fourth Military Medical University Xi'an 710038, Shaanxi, China.

Increasing evidence shows that hypoxia is a cause of male infertility, and hypoxia may be related to oxidative stress (OS). Cistanoside (Cis) is a phenylethanoid glycoside compound that can be extracted from and possesses various biological functions. This study aimed to investigate the protective effects of Cis on reproductive damage induced by hypoxia and explore the specific underlying mechanisms. Cell and animal hypoxia experimental models were constructed, and the protective effects of different subtypes of Cis on the male reproductive system were assessed both and . The results indicated that hypoxia significantly reduced the viability of GC-1 cells through cell cycle arrest and apoptosis activation, which were associated with increased OS. Moreover, Cis showed strong antioxidative effects both and , significantly restoring antioxidant enzyme activities and downregulating reactive oxygen species (ROS) levels while increasing cell viability and decreasing apoptosis. Importantly, the Cis subtypes (Cis-A, Cis-B, Cis-C and Cis-H) studied herein all showed certain antioxidant effects, among which the effects of Cis-B were the most significant. This study demonstrates that Cis markedly attenuates the harmful effects of hypoxia-induced OS by affecting antioxidant enzyme activities in testes and GC-1 cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205727PMC
May 2021

Association of Blood Pressure, White Matter Lesions, and Regional Cerebral Blood Flow.

Med Sci Monit 2021 Jun 21;27:e929958. Epub 2021 Jun 21.

Department of Neurology, The Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang, Jiangsu, China (mainland).

BACKGROUND At present, the association between blood pressure, regional cerebral blood flow, and white matter lesions is not well understood. MATERIAL AND METHODS A total of 147 subjects aged from 40 to 80 years were assessed by the Fazekas score for white matter lesions, CT perfusion imaging for regional cerebral blood flow, and 24-h ambulatory blood pressure monitoring for blood pressure level and rhythm. Logistic regression analysis was used to obtain the odds ratio and 95% confidence interval between Fazekas scores and relevant factors. The relationship between blood pressure index and regional cerebral blood flow was analyzed through cubic curve estimation. RESULTS Fazekas score was negatively correlated with regional cerebral blood flow (r=-0.801; r=-0.831, P<0.001). For subcortical lesion, the regional cerebral blood flow of Fazekas grade 0 was 1.976 times that of Fazekas grade 3 (OR=1.976, 95% CI=1.576-2.477), and for periventricular lesion, the regional cerebral blood flow of Fazekas grade 0 was 2.034 times that of Fazekas grade 3 (OR=2.034, 95% CI=1.602-2.583). Increased nighttime systolic blood pressure may be more dangerous (OR=1.112, 95% CI=1.059-1.169). The day-night systolic blood pressure ratio (OR=0.801, 95% CI 0.711-0.902) and the day-night diastolic blood pressure ratio (OR=0.876, 95% CI 0.807-0.950) were significantly correlated with Fazekas score. CONCLUSIONS The decrease of white matter regional cerebral blood flow caused by hypertension is probably one of the important causes of white matter lesions. Patients with white matter lesions should also pay attention to the rhythm of blood pressure when controlling hypertension, especially if their blood pressure is too high or too low at night.
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http://dx.doi.org/10.12659/MSM.929958DOI Listing
June 2021

Sporadic and Periodic Interictal Discharges in Critically Ill Children: Seizure Associations and Time to Seizure Identification.

J Clin Neurophysiol 2021 May 5. Epub 2021 May 5.

Division of Epilepsy and Neurophysiology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.; and Department of Critical Care Medicine and Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.

Purpose: We evaluated interictal discharges (IEDs) as a biomarker for the time to development of electrographic seizures (ES).

Methods: Prospective observational study of 254 critically ill children who underwent continuous electroencephalography (cEEG) monitoring. We excluded neonates and patients with known epilepsy or the sole cEEG indication to characterize events. Interictal discharges included sporadic epileptiform discharges and periodic and rhythmic patterns. Sporadic epileptiform discharges were categorized as low frequency (rare [<1/hour] and occasional [≥1/hour but <1/minute]) and high frequency (frequent, [≥1/minute] and abundant [≥1/10 seconds]). Time variables included time from cEEG start to first IED and time between first IED and ES.

Results: Interictal discharges were present in 33% (83/254) of patients. We identified ES in 20% (50/254), and 86% (43/50) had IEDs. High-frequency sporadic epileptiform discharges (odds ratio [OR], 35; 95% confidence interval [CI], 14.5-88; P < 0.0001) and lateralized periodic discharges (OR, 27; 95% CI, 7.3-100; P < 0.0001) were associated with ES. Mildly abnormal EEG background without IEDs or background asymmetry was associated with the absence of seizures (OR, 0.1; 95% CI, 0.04-0.3; P < 0.0001). Time from cEEG start to first IED was 36 minutes (interquartile range, 3-131 minutes), and time between first IED and ES was 9.6 minutes (interquartile range, 0.6-165 minutes).

Conclusions: Interictal discharges are associated with ES and are identified in the first 3 hours of cEEG. High-frequency sporadic epileptiform discharges and periodic patterns have the highest risk of ES. Our findings define a window of high seizure risk after the identification of IEDs in which to allocate resources to improve seizure identification and subsequent treatment.
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http://dx.doi.org/10.1097/WNP.0000000000000860DOI Listing
May 2021

Rapid detection of cellulose and hemicellulose contents of corn stover based on near-infrared spectroscopy combined with chemometrics.

Appl Opt 2021 May;60(15):4282-4290

The feasibility of near-infrared spectroscopy (NIRS) combined with chemometrics for the rapid detection of the cellulose and hemicellulose contents in corn stover is discussed. Competitive adaptive reweighted sampling (CARS) and genetic simulated annealing algorithm (GSA) were combined (CARS-GSA) to select the characteristic wavelengths of cellulose and hemicellulose and to reduce the dimensionality and multicollinearity of the NIRS data. The whole spectra contained 1845 wavelength variables. After CARS-GSA optimization, the number of characteristic wavelengths of cellulose (hemicellulose) was reduced to 152 (260), accounting for 8.24% (14.09%) of all wavelengths. The coefficients of determination of the regression models for predicting the cellulose and hemicellulose contents were 0.968 and 0.996, the root mean square errors of prediction (RMSEPs) were 0.683 and 0.648, and the residual predictive deviations (RPDs) were 5.213 and 16.499, respectively. The RMSEP of the cellulose and hemicellulose regression models was 0.152 and 0.190 lower for CARS-GSA than for the full-spectrum, and the RPD was increased by 0.949 and 3.47, respectively. The results showed that the CARS-GSA model substantially reduced the number of characteristic wavelengths and significantly improved the predictive ability of the regression model.
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http://dx.doi.org/10.1364/AO.418226DOI Listing
May 2021

Analysis of the application of contrast-enhanced ultrasound-guided prostate biopsy in early diagnosis of prostate cancer.

Minerva Med 2021 Jun 18. Epub 2021 Jun 18.

Department of Ultrasound, The Third Hospital of Hebei Medical University, Shijiazhuang, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07622-9DOI Listing
June 2021

Alternatones A and B, two polyketides possessing novel skeletons from entophyte L-10.

J Asian Nat Prod Res 2021 Jun 18:1-8. Epub 2021 Jun 18.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Nanjing University, Nanjing 210023, China.

On our ongoing searching for bioactive natural products derived from entophytes, two polyketides possessing novel skeletons, alternatones A-B (-), were identified from the culture of L-10. Their structures were established by a combination of spectroscopic and single-crystal X-ray diffraction with Cu K radiation. Alternatone A () exhibited cytotoxic activity against human hepatoma carcinoma HepG-2 cell line. The putative biosynthetic pathways for compounds - were also proposed.
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http://dx.doi.org/10.1080/10286020.2021.1935893DOI Listing
June 2021

A pig BodyMap transcriptome reveals diverse tissue physiologies and evolutionary dynamics of transcription.

Nat Commun 2021 06 17;12(1):3715. Epub 2021 Jun 17.

Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China.

A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter-enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.
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http://dx.doi.org/10.1038/s41467-021-23560-8DOI Listing
June 2021

Key factors driving the fate of antibiotic resistance genes and controlling strategies during aerobic composting of animal manure: A review.

Sci Total Environ 2021 Jun 8;791:148372. Epub 2021 Jun 8.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Occurrence of antibiotic resistance genes (ARGs) in animal manure impedes the reutilization of manure resources. Aerobic composting is potentially effective method for resource disposal of animal manure, but the fate of ARGs during composting is complicated due to the various material sources and different operating conditions. This review concentrates on the biotic and abiotic factors influencing the variation of ARGs in composting and their potential mechanisms. The dynamic variations of biotic factors, including bacterial community, mobile genetic elements (MGEs) and existence forms of ARGs, are the direct driving factors of the fate of ARGs during composting. However, most key abiotic indicators, including pH, moisture content, antibiotics and heavy metals, interfere with the richness of ARGs indirectly by influencing the succession of bacterial community and abundance of MGEs. The effect of temperature on ARGs depends on whether the ARGs are intracellular or extracellular, which should be paid more attention. The emergence of various controlling strategies renders the composting products safer. Four potential removal mechanisms of ARGs in different controlling strategies have been concluded, encompassing the attenuation of selective/co-selective pressure on ARGs, killing the potential host bacteria of ARGs, reshaping the structure of bacterial community and reducing the cell-to-cell contact of bacteria. With the effective control of ARGs, aerobic composting is suggested to be a sustainable and promising approach to treat animal manure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148372DOI Listing
June 2021

Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation.

JCI Insight 2021 Jun 17. Epub 2021 Jun 17.

Shanghai East Hospital, Tongji University, Shanghai, China.

Background: Abdominal pain and constipation are two main symptoms in patients with constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to investigate the effects and possible mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) in patients with IBS-C.

Methods: Forty-two patients with IBS-C were randomized into a 4-week sham-taVNS or taVNS treatment. The primary outcomes were complete spontaneous bowel movements per week (CSBMs/week) and visual analog scale (VAS) for abdominal pain. High-resolution anorectal manometry (HRAM) was performed to evaluate anorectal motor and sensory function. Cytokines and brain gut peptides were analyzed in blood samples. Electrocardiogram (ECG) was recorded for the assessment of autonomic function.

Results: Compared with sham-taVNS, (1) taVNS increased CSBMs/week (P = 0.001) and decreased VAS pain score (P = 0.001); (2) It also improved quality of life (P = 0.020) and decreased IBS symptom score (P = 0.001); (3) taVNS improved rectoanal inhibitory reflex (P=0.014), and improved rectal sensation (P <0.04); (4) taVNS also decreased a number of pro-inflammatory cytokines and serotonin in circulation; (5) taVNS enhanced vagal activity (P = 0.040). The vagal activity was weakly correlated with the CSBMs/week (r = 0.391; P = 0.010) and the VAS pain score (r = -0.347; P = 0.025).

Conclusions: Noninvasive taVNS improves both constipation and abdominal pain in patients with IBS-C. The improvement in IBS-C symptoms might be attributed to the integrative effects of taVNS on intestinal functions mediated via the autoimmune mechanisms.

Trial Registration: www.chictr.org.cn ChiCTR2000029644.

Funding: National Natural Science Foundation of China (Grant No. 81970538 for Fei Liu).
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http://dx.doi.org/10.1172/jci.insight.150052DOI Listing
June 2021

Overproduction of D-pantothenic acid via fermentation conditions optimization and isoleucine feeding from recombinant .

3 Biotech 2021 Jun 24;11(6):295. Epub 2021 May 24.

The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, 310014 People's Republic of China.

D-pantothenic acid (D-PA), as a crucial vitamin, is widely used in food, animal feed, cosmetics, and pharmaceutical industries. In our previous work, recombinant W3110 for production of D-PA was constructed through metabolic pathway modification. In this study, to enhance D-PA production, statistical optimization techniques including Plackett-Burman (PB) design and Box-Behnken design (BBD) first were adopted to optimize the culture condition. The results showed that the glucose, β-alanine and (NH)SO have the most significant effects on D-PA biosynthesis. The response surface model based on BBD predicted that the optimal concentration is glucose 56.0 g/L, β-alanine 2.25 g/L and (NH4)SO 11.8 g/L, the D-PA titer increases from 3.2 g/L to 6.73 g/L shake flask fermentation. For the fed-batch fermentation in 5 L fermenter, the isoleucine feeding strategy greatly increased the titer and productivity of D-PA. As a result, titer (31.6 g/L) and productivity (13.2 g/L·d) of D-PA were achieved, they increased by 4.66 times and 2.65 times, respectively, compared with batch culture. At the same time, the accumulation of acetate reduced from 29.79 g/L to 8.55 g/L in the fed-batch fermentation. These results demonstrated that the optimization of medium composition and the cell growth rate are important to increase the concentration of D-PA for microbial fermentation. This work laid the foundation for further research on the application of D-PA microbial synthesis.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02773-0.
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http://dx.doi.org/10.1007/s13205-021-02773-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144260PMC
June 2021

Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis.

Int J Nanomedicine 2021 9;16:4001-4016. Epub 2021 Jun 9.

School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People's Republic of China.

Background: Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy.

Methods: Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel "BEL-7402+HUVEC" co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test.

Results: The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery.

Conclusion: CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.
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http://dx.doi.org/10.2147/IJN.S309804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200177PMC
June 2021

Whole-genome sequencing suggests a role of MIF in the pathophysiology of TEMPI syndrome.

Blood Adv 2021 Jun;5(12):2563-2568

Institute of Hematology.

TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a newly defined multisystemic disease with its pathophysiology largely unknown. Here, we report the whole-genome sequencing (WGS) analysis on the tumor-normal paired cells from a patient with TEMPI syndrome. WGS revealed somatic nonsynonymous single-nucleotide variants, including SLC7A8, NRP2, and AQP7. Complex structural variants of chromosome 2 were found, particularly within regions where some putative oncogenes reside. Of potential clinical relevance, duplication of 22q11.23 was identified, and the expression of the located gene macrophage migration inhibitory factor (MIF) was significantly upregulated in 3 patients with TEMPI syndrome. Importantly, the level of serum MIF in one patient with TEMPI syndrome was significantly decreased in accordance with the downtrend of plasma cells, M-protein, hemoglobin, and erythropoietin and the improvement of telangiectasias, perinephric fluid collections, and intrapulmonary shunting after treatment with plasma cell-directed therapy. In conclusion, our study provides insights into the genomic landscape and suggests a role of MIF in the pathophysiology of TEMPI syndrome.
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http://dx.doi.org/10.1182/bloodadvances.2020003783DOI Listing
June 2021

Selenium deficiency causes apoptosis through endoplasmic reticulum stress in swine small intestine.

Biofactors 2021 Jun 15. Epub 2021 Jun 15.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Selenium (Se) plays a crucial role in intestinal health. However, the specific mechanism by which deficiency of Se causes intestinal damage remains unclear. This study was to explore whether Se deficiency can cause ER stress and induce apoptosis in swine small intestine. We established the Se deficiency swine model in vivo and the intestinal epithelial (IPEC-J2) cell Se deficiency model in vitro. The results of morphological observation showed that Se deficiency caused structural damage in intestinal villi and the decrease of goblet cell structure. The apoptotic characteristics such as nucleolar condensation, mitochondrial swelling, and apoptotic bodies were observed in the IPEC-J2 cells. The results of acridine orange/ethidium bromide and mitochondrial membrane potential fluorescence staining in vitro showed that there were more apoptotic cells in the Se-deficiency group than that in the control group. The protein and/or mRNA expression levels of Bax, Bcl-2, caspase 3, caspase 8, caspase 9, cytc, PERK, ATF6, IRE, XBP1, CHOP, GRP78, which are related to ER stress-apoptosis pathway, were significantly increased in the Se-deficient group which compared with the control group in vivo and in vitro were consistent. These results indicated that Se deficiency induced ER stress and increased the apoptosis in swine small intestine and IPEC-J2 cells and then caused the damage in swine small intestinal tissue. Besides, the results of gene expressions in our experiment proved that ER stress induced by Se deficiency promoted apoptosis. These results filled the blank in the mechanism of Se deficiency-induced intestinal injury in swine.
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http://dx.doi.org/10.1002/biof.1762DOI Listing
June 2021

Effects of cranberry beverages on oxidative stress and gut microbiota in subjects with infection: a randomized, double-blind, placebo-controlled trial.

Food Funct 2021 Jun 15. Epub 2021 Jun 15.

Institute of Nutrition and Health, School of Public Health, Qingdao University, 38 Dengzhou Road, Qingdao, Shandong, China.

Helicobacter pylori-induced oxidative stress plays an important role in gastric diseases. H. pylori disturbs gut microbiota. The objective is to investigate the effects of cranberry beverages on oxidative stress biomarkers and gut microbiota in H. pylori positive subjects. 171 H. pylori positive participants were randomly assigned to one of the three groups: high-dose (HCb; 480 mL cranberry beverage), low-dose (LCb; 240 mL cranberry beverage plus 240 mL placebo) and placebo (480 mL). Subjects consumed the beverages daily for 4 weeks. Fasting blood samples were analyzed for oxidative stress biomarkers. The intestinal microbiome was analyzed by 16S rRNA sequencing. Compared with the placebo, HCb resulted in a significantly higher increase of total antioxidant capacity (mean ± SD: 1.39 ± 1.69 IU mL-1 vs. 0.34 ± 1.73 IU mL-1; p < 0.001) and a higher decrease of the lipid peroxidation product malondialdehyde (-7.29 ± 10.83 nmol mg-1 vs. -0.84 ± 15.66 nmol mg-1; p = 0.025). A significant dose-dependent effect on the elevation of superoxide dismutase was observed (p < 0.001). Microbiome data showed that consuming HCb and LCb led to a significant reduction of Pseudomonas (p < 0.05). In conclusion, the current research showed that consuming cranberry beverages significantly improved the antioxidant status in H. pylori positive subjects, which may be related to the reshaping of gut microbiota.
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http://dx.doi.org/10.1039/d1fo00467kDOI Listing
June 2021

DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

JAMA Neurol 2021 Jun 14. Epub 2021 Jun 14.

Yale Center for Genome Analysis, West Haven, Connecticut.

Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.

Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.

Design, Setting, And Participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort.

Main Outcomes And Measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue.

Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways.

Conclusions And Relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.
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http://dx.doi.org/10.1001/jamaneurol.2021.1681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204259PMC
June 2021

Study on the Fluidization Quality Characterization Method and Process Intensification of Fine Coal Separation in a Vibrated Dense Medium Fluidized Bed.

ACS Omega 2021 Jun 25;6(22):14268-14277. Epub 2021 May 25.

School of Chemistry and Environmental Engineering, North China Institute of Science & Technology, Sanhe 065201, China.

Uniform and stable bed density is the basis of efficient coal separation by a gas-solid dense medium fluidized bed. The traditional air dense medium fluidized bed (ADMFB) is a kind of bubbling bed. By introducing vibration energy, a vibrated dense medium fluidized bed (VDMFB) with uniform and stable bed density can be formed, where the bubble merger is suppressed, the gas-solid contact can is strengthened, and the fluidization quality is also improved. In this paper, the transfer process of vibration energy in a fluidized bed is studied in detail. By calculating the coherence of pressure signals induced by vibration energy and bubbles at different bed heights, the suppression effect of vibration energy on bubble merger is analyzed. The coefficient to quantitatively evaluate the improvement effect of vibration energy on the fluidization quality is proposed. The differences and incentives of density uniformity and stability in different height bed areas have been clarified under different vibration parameters and gas flow parameters. It is proposed that the optimal separation bed height area of VDMFB is about = 40-150 mm. The separation effect of the ADMFB and the VDMFB on 1-6 mm fine coal was compared. The results show that, compared with the ADMFB, the VDMFB reduces the separation probable error, , from 0.134 to 0.083 g/cm, and the ash content of the clean coal is reduced from 18.83 to 14.97%. The vibration energy significantly improves the fluidization quality of the ADMFB and the separation effect of fine coal.
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http://dx.doi.org/10.1021/acsomega.1c01034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190785PMC
June 2021

Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells.

Front Oncol 2021 26;11:667920. Epub 2021 May 26.

Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

The cGAS (GMP-AMP synthase)-mediated senescence-associated secretory phenotype (SASP) and DNA-induced autophagy (DNA autophagy) have been extensively investigated in recent years. However, cGAS-mediated autophagy has not been elucidated in cancer cells. The described investigation revealed that active DNA autophagy but not SASP activity could be detected in the BT-549 breast cancer cell line with high micronucleus (MN) formation. DNA autophagy was identified as selective autophagy of free genomic DNA in the cytoplasm but not nucleophagy. The process of DNA autophagy in the cytosol could be initiate by cGAS and usually cooperates with SQSTM1-mediated autophagy of ubiquitinated histones. Cytoplasmic DNA, together with nuclear proteins such as histones, could be derived from DNA replication-induced nuclear damage and MN collapse. The inhibition of autophagy through chemical inhibitors as well as the genomic silencing of cGAS or SQSTM1 could suppress the growth and survival of cancer cells, and induced DNA damage could increase the sensitivity to these inhibitors. Furthermore, expanded observations of several other kinds of human cancer cells indicated that high relative DNA autophagy or enhancement of DNA damage could also increase or sensitize these cells to inhibition of DNA autophagy.
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http://dx.doi.org/10.3389/fonc.2021.667920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189927PMC
May 2021

MicroRNA 379 Regulates Klotho Deficiency-Induced Cardiomyocyte Apoptosis Via Repression of Smurf1.

Hypertension 2021 Jun 14:HYPERTENSIONAHA12016888. Epub 2021 Jun 14.

From the Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis (K.C., B.Z., Z.S.).

is an aging-suppressor gene. gene deficiency impairs heart function leading to heart failure, but the underlying mechanism remains poorly understood. MicroRNAs are increasingly recognized to play important roles in the pathogenesis of cardiomyopathy. The objective of this study is to investigate whether microRNA 379 (Mir379) regulates Klotho deficiency-associated cardiomyocyte apoptosis. Using inducible Cre-Loxp recombination technology, we first found that kidney-specific deletion of the gene caused heart failure. Using microRNA sequencing analysis, we found that Mir379 may be a target of Klotho. In cultured H9c2 heart cells, we found that treatment with Klotho-free medium increased Mir379 levels and induced apoptosis. To test whether Mir379 mediates Klotho deficiency-induced apoptosis, H9c2 cells were transfected with Mir379 inhibitor. Interestingly, Mir379 inhibitor (anti-Mir379) prevented Klotho deficiency-induced H9c2 cell apoptosis. On the contrary, Mir379 mimic itself caused apoptosis in H9c2 cells. These findings suggest that Mir379 may mediate Klotho deficiency-induced apoptosis in H9C2 cells. Using the mRNA-miRNA target interaction assay, we found that Smurf1(SMAD specific E3 ubiquitin protein ligase 1) mRNA contained the 3-UTR binding site for Mir379. Importantly, Mir379 mimic suppressed Smurf1 expression, and the Mir379 mimic-induced apoptosis can be rescued by treatment with exogenous Smurf1 protein. Therefore, Smurf1 repression may be involved in Mir379-induced H9c2 cells apoptosis. In conclusion, Mir379 may mediate Klotho deficiency-associated cardiomyocyte apoptosis through repression of Smurf1 which is required for Mir379-induced apoptotic cell death. Mir379 may be a potential therapeutic target for cardiomyocyte apoptosis-associated heart failure due to Klotho deficiency.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16888DOI Listing
June 2021

Colorimetry and SERS dual-mode sensing of serotonin based on functionalized gold nanoparticles.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 5;261:120057. Epub 2021 Jun 5.

College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China. Electronic address:

In this study, we reported a colorimetry and SERS dual-mode sensing of serotonin (5-HT) based on functionalized gold nanoparticles (AuNPs). Based on the amino and hydroxyl groups in 5-HT can react with dithiobis succinimidyl propionate (DSP) and N-acetyl-L-cysteine (NALC) respectively, we synthesized two kinds of functionalized AuNPs (DSP-AuNPs and NALC-AuNPs). A double interaction between functionalized nanoparticles and the hydroxyl and the amino group of serotonin led to interparticle-crosslinking aggregation. The aggregation of the two functionalized AuNPs can cause the plasmon coupling of AuNPs resulting in a color change visible to the naked eye and the enlargement of SERS "hot spot" area and the enhancement of SERS signal. Furthermore, two kinds of functionalized AuNPs can specifically recognize 5-HT and effectively reduce the interference of biomolecules with similar structure to 5-HT in the experiment. This dual-mode system has the advantages of low detection limit, high sensitivity and good selectivity, and the detection limit is 0.15 nmol L. Besides, the system was applied to the determination of 5-HT content in human serum, and the relative standard deviation (RSD) was lower than 3.75%, which indicated that the system had a good application prospect in the determination of biological samples.
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http://dx.doi.org/10.1016/j.saa.2021.120057DOI Listing
June 2021

Epidemic of HIV infection among persons who inject drugs in mainland China: a series, cross-sectional study.

Harm Reduct J 2021 Jun 12;18(1):63. Epub 2021 Jun 12.

School of Public Health, Peking University, Beijing, 100191, China.

Background: Studies have suggested that the injection drug use (IDU) was no longer the main transmission route of HIV/AIDS in China. However, there has never been a study to assess the national HIV epidemic among persons who inject drugs (PWIDs) based on a nationwide database.

Methods: PWIDs among new entrants in detoxification centers with HIV test results were extracted from the 2008-2016 National Dynamic Management and Control Database for Persons Who Use Drugs (NDMCD). Logistic regressions were used to analyze factors associated with HIV infection, and joinpoint regression were used to examine trends in the HIV prevalence.

Results: A total of 103,619 PWIDs among new entrants tested for HIV in detoxification centers between 2008 and 2016 were included in the analysis. The HIV prevalence was 5.0% (n = 5167) among PWIDs. A U-shaped curve of the HIV prevalence decreased from 4.9% in 2008 to 3.3% in 2010 (Annual Percent Change [APC] - 20.6, 95% CI - 32.5 to - 6.7, p < 0.05) and subsequently increased from 3.3% in 2010 to 8.6% in 2016 (APC 17.9, 95% CI 14.5-21.4, p < 0.05) was observed. The HIV prevalence in west regions in China all presented decreased trends, while central and eastern regions presented increased trends.

Conclusions: Although the HIV prevalence has been declining in general population, the HIV prevalence among PWIDs has shown an increasing trend since 2010. Current policies on HIV control in PWIDs should be reassessed.
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http://dx.doi.org/10.1186/s12954-021-00511-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199561PMC
June 2021

Candidate gene screening for lipid deposition using combined transcriptomic and proteomic data from Nanyang black pigs.

BMC Genomics 2021 Jun 12;22(1):441. Epub 2021 Jun 12.

National Engineering Laboratory for Animal Breeding/Beijing Key Laboratory for Animal Genetic Improvement, China Agricultural University, Beijing, China.

Background: Lower selection intensities in indigenous breeds of Chinese pig have resulted in obvious genetic and phenotypic divergence. One such breed, the Nanyang black pig, is renowned for its high lipid deposition and high genetic divergence, making it an ideal model in which to investigate lipid position trait mechanisms in pigs. An understanding of lipid deposition in pigs might improve pig meat traits in future breeding and promote the selection progress of pigs through modern molecular breeding techniques. Here, transcriptome and tandem mass tag-based quantitative proteome (TMT)-based proteome analyses were carried out using longissimus dorsi (LD) tissues from individual Nanyang black pigs that showed high levels of genetic variation.

Results: A large population of Nanyang black pigs was phenotyped using multi-production trait indexes, and six pigs were selected and divided into relatively high and low lipid deposition groups. The combined transcriptomic and proteomic data identified 15 candidate genes that determine lipid deposition genetic divergence. Among them, FASN, CAT, and SLC25A20 were the main causal candidate genes. The other genes could be divided into lipid deposition-related genes (BDH2, FASN, CAT, DHCR24, ACACA, GK, SQLE, ACSL4, and SCD), PPARA-centered fat metabolism regulatory factors (PPARA, UCP3), transcription or translation regulators (SLC25A20, PDK4, CEBPA), as well as integrin, structural proteins, and signal transduction-related genes (EGFR).

Conclusions: This multi-omics data set has provided a valuable resource for future analysis of lipid deposition traits, which might improve pig meat traits in future breeding and promote the selection progress in pigs, especially in Nanyang black pigs.
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http://dx.doi.org/10.1186/s12864-021-07764-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201413PMC
June 2021

Identification of prognostic markers for hepatocellular carcinoma based on the epithelial-mesenchymal transition-related gene BIRC5.

BMC Cancer 2021 Jun 10;21(1):687. Epub 2021 Jun 10.

Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.

Background: The baculoviral IAP repeat containing 5 (BIRC5) related to epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). However, it remains unclear whether BIRC5-related genes can be used as prognostic markers of HCC.

Methods: Kaplan-Meier (K-M) survival curve was used to assess the Overall Survival (OS) of high- and low-expression group divided by the median of BIRC5 expression. The differentially expressed genes (DEGs) between the two groups were screened using the limma package, and performed the functional enrichment analysis by the clusterProfiler package. WGCNA was used to analyze the relationship of the module and the clinical traits. The risk signature was constructed by univariate and multivariate Cox regression analyses and the enrichment analysis of genes in the risk signature was performed by the Intelligent pathway analysis (IPA). The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) were used to estimate the clinical significance of the risk groups.

Results: BIRC5 was high-expressed in HCC samples and associated with a poor prognosis (p-value < 0.0001). WGCNA screened 180 module genes which were overlapped with the 241 DEGs, ultimately getting 33 candidate genes. After the Cox regression analyses, CENPA, CDCA8, EZH2, KIF20A, KPNA2, CCNB1, KIF18B and MCM4 were preserved and used to construct risk signature, followed by calculating the risk score. The patients in high-risk groups stratified by median of the risk score were associated with a poor prognosis. The risk score had high accuracy [the area under the curve (AUC) > 0.72] and was closely associated with clinicopathological characteristics of HCC patients. IPA suggested that the 8 genes were enriched in Cancer and Immunological disease related pathways. IPS and TIDE score indicated that the genes in low-risk group could cause an immune response, and patients in the low-risk group may be more sensitive to the immune checkpoint blockade (ICB) therapy.

Conclusion: The risk score constructed by the 8 genes could not only predict the clinical outcome but also distinguish the cohort of ICB therapy in HCC, which exerted a vital value in treatment and prognosis of HCC.
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http://dx.doi.org/10.1186/s12885-021-08390-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194133PMC
June 2021

Segmented Microfluidics-Based Packing Technology for Chromatographic Columns.

Anal Chem 2021 Jun 10;93(24):8450-8458. Epub 2021 Jun 10.

Department of Chemistry and The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Nanoflow liquid chromatography-mass spectrometry (NanoLC-MS) has become the method of choice for the analysis of complex biological systems, especially when the available sample amount is limited. The preparation of high-performance capillary columns for nanoLC use is still a technical challenge. Here, we report a segmented microfluidic method for the preparation of packed capillary columns, where liquid segments were used as soft, dynamic, and well-dispersed slurry reservoirs for carrying and delivering micrometer packing particles. Based on this microfluidic packing technology, the column bed was assembled layer-by-layer at a 50 μm resolution, and ultralong capillary columns of 3, 5, and 10 m were fabricated in such a manner. The microfluidically packed columns demonstrated excellent separation efficiencies of 116 000 plates/m. The higher efficiencies obtained at higher slurry concentrations also indicate that a high-quality packed bed can be obtained without sacrificing the packing speed. Kinetic performance limit analysis shows that the microfluidic packed columns have higher peak capacity production efficiency in the high-resolution region, presenting an improved separation impedance of 2800, which is significantly better than columns packed with the conventional slurry packing method. In comparison with a commercial nanoLC column, a 5 m long microfluidic packed column was evaluated for proteomic analysis using a standard HeLa protein digest and presented 261% improvement in peptide identification capability, resulting in significantly enhanced protein identification confidence.
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http://dx.doi.org/10.1021/acs.analchem.1c00545DOI Listing
June 2021

Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein.

Front Mol Biosci 2021 24;8:665552. Epub 2021 May 24.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Platelet-derived growth factor C (PDGF-C) is a member of the PDGF/VEGF (vascular endothelial growth factor) family, which includes proteins that are well known for their mitogenic effects on multiple cell types. Glycosylation is one of the most important forms of posttranslational modification that has a significant impact on secreted and membrane proteins. Glycosylation has many well-characterized roles in facilitating protein processing and contributes to appropriate folding, conformation, distribution, and stability of proteins that are synthesized intracellularly in the endoplasmic reticulum (ER) and Golgi apparatus. Although the general process and functions of glycosylation are well documented, there are most likely others yet to be discovered, as the glycosylation of many potential substrates has not been characterized. In this study, we report that the PDGF-C protein is glycosylated at three sites, including Asn25, Asn55, and Asn254. However, we found that mutations at any of these sites do not affect the protein expression or secretion. Similarly, disruption of PDGF-C glycosylation had no impact on its progression through the ER and Golgi apparatus. However, the introduction of a mutation at Asn254 (N254 A) prevents the activation of full-length PDGF-C and its capacity for signaling the PDGF receptor. Our findings reveal that glycosylation affects PDGF-C activation rather than the protein synthesis or processing. This study characterizes a crucial modification of the PDGF-C protein, and may shed new light on the process and function of glycosylation.
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http://dx.doi.org/10.3389/fmolb.2021.665552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181125PMC
May 2021

Mechanistic insights into the R-loop formation and cleavage in CRISPR-Cas12i1.

Nat Commun 2021 06 9;12(1):3476. Epub 2021 Jun 9.

The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.

Cas12i is a newly identified member of the functionally diverse type V CRISPR-Cas effectors. Although Cas12i has the potential to serve as genome-editing tool, its structural and functional characteristics need to be investigated in more detail before effective application. Here we report the crystal structures of the Cas12i1 R-loop complexes before and after target DNA cleavage to elucidate the mechanisms underlying target DNA duplex unwinding, R-loop formation and cis cleavage. The structure of the R-loop complex after target DNA cleavage also provides information regarding trans cleavage. Besides, we report a crystal structure of the Cas12i1 binary complex interacting with a pseudo target oligonucleotide, which mimics target interrogation. Upon target DNA duplex binding, the Cas12i1 PAM-interacting cleft undergoes a remarkable open-to-closed adjustment. Notably, a zipper motif in the Helical-I domain facilitates unzipping of the target DNA duplex. Formation of the 19-bp crRNA-target DNA strand heteroduplex in the R-loop complexes triggers a conformational rearrangement and unleashes the DNase activity. This study provides valuable insights for developing Cas12i1 into a reliable genome-editing tool.
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http://dx.doi.org/10.1038/s41467-021-23876-5DOI Listing
June 2021

The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes.

Proc Natl Acad Sci U S A 2021 Jun;118(24)

Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;

DNA replication is dramatically slowed down under replication stress. The regulation of replication speed is a conserved response in eukaryotes and, in fission yeast, requires the checkpoint kinases Rad3 and Cds1 However, the underlying mechanism of this checkpoint regulation remains unresolved. Here, we report that the Rad3-Cds1 checkpoint directly targets the Cdc45-MCM-GINS (CMG) replicative helicase under replication stress. When replication forks stall, the Cds1 kinase directly phosphorylates Cdc45 on the S275, S322, and S397 residues, which significantly reduces CMG helicase activity. Furthermore, in -mutated cells, the CMG helicase and DNA polymerases are physically separated, potentially disrupting replisomes and collapsing replication forks. This study demonstrates that the intra-S phase checkpoint directly regulates replication elongation, reduces CMG helicase processivity, prevents CMG helicase delinking from DNA polymerases, and therefore helps preserve the integrity of stalled replisomes and replication forks.
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http://dx.doi.org/10.1073/pnas.2019183118DOI Listing
June 2021

Applications of single-cell sequencing in cancer research: progress and perspectives.

J Hematol Oncol 2021 Jun 9;14(1):91. Epub 2021 Jun 9.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, 200032, China.

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.
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http://dx.doi.org/10.1186/s13045-021-01105-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190846PMC
June 2021

Association of KCTD15 gene with fat deposition in pigs.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 9. Epub 2021 Jun 9.

National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.

KCTD15 is associated with body mass index and fat deposition in humans, mice and chickens. However, the function of KCTD15 in pig fat deposition remains unclear. In this study, we cloned and analysed the cDNA sequence of porcine KCTD15. The full length of the mRNA sequence of KCTD15 is 4,091 bp, encoding 283 amino acids. The protein is hydrophilic, it has a relative molecular mass of about 31.9 kDa and an isoelectric point of 7.09 with no signal peptide sequence or transmembrane structure. Expression analysis showed that KCTD15 expression level was significantly higher in the tissues of Large White pigs (LW) than in those of Tibetan pigs (TP) and Diannan Small-ear pigs (DN) at 6 months of age, whereas its expression level in embryonic tissues of LW at 60 days was lower than that in tissues of TP and Wujin pigs (WJ). In pig primary adipocytes, the expression level of KCTD15 is high in the early stage of differentiation and gradually decreases in later stages. Additionally, the single-nucleotide polymorphism (SNP) site T-2030C (T/C mutation, located 2,030 bp upstream of the start codon) showed a dominant allele T with high promoter activity in the LW population and a dominant allele C in the TP and WJ populations. Our results indicate that KCTD15 is involved in pig fat deposition and that T-2030C is an important regulatory site for transcriptional activity, affecting fat deposition.
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http://dx.doi.org/10.1111/jpn.13587DOI Listing
June 2021