Publications by authors named "Shan Jiang"

928 Publications

IL10RB as a key regulator of COVID-19 host susceptibility and severity.

medRxiv 2021 Jun 2. Epub 2021 Jun 2.

Background: Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step.

Methods: We integrate COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbargen signatures to identify candidate genes and compounds that reverse the predicted gene expression dysregulation associated with COVID-19 susceptibility. The top candidate gene is validated by testing both its GReX and observed blood transcriptome association with COVID-19 severity, as well as by perturbation to quantify effects on viral load and molecular pathway dysregulation. We validate the drug repositioning analysis by examining whether the top candidate compounds decrease COVID-19 incidence based on epidemiological evidence.

Results: We identify as the top key regulator of COVID-19 host susceptibility. Predicted GReX up-regulation of and higher expression in COVID-19 patient blood is associated with worse COVID-19 outcomes. IL10RB overexpression is associated with increased viral load and activation of immune-related molecular pathways. Azathioprine and retinol are prioritized as candidate compounds to reduce the likelihood of testing positive for COVID-19.

Conclusions: We establish an integrative data-driven approach for gene target prioritization. We identify and validate as a suitable molecular target for modulation of COVID-19 host susceptibility. Finally, we provide evidence for a few readily available medications that would warrant further investigation as drug repositioning candidates.
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http://dx.doi.org/10.1101/2021.05.31.21254851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183086PMC
June 2021

The effects of cryopreservation on the acrosome structure, enzyme activity, motility, and fertility of bovine, ovine, and goat sperm.

Anim Reprod 2021 Mar 8;17(4):e20200219. Epub 2021 Mar 8.

College of Life Science and The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, P.R. China.

The study was designed to investigate the effects of cryopreservation on bovine, ovine, and goat sperm motility, acrosome structure, enzyme activity, and fertilization ability. Percentage of sperm with hyaluronidase enzyme (HYD) activity was detected by a modified sodium hyaluronate-gelatin membrane. The N-α-benzoyl-DL-arginine-p-nitroanilide (BNPNA) method was used to assess the sperm acrosome enzyme (ACE). The mean percentage of sperm acrosome integrity dropped significantly ( < 0.01) after cryopreservation. The ACE activity of bovine sperm (100.48) was higher ( < 0.01) than that of ovine (57.88) or goat sperm (50.30), while the percentage of sperm with HYD activity of bovine (71.10%) and ovine (67.60%) sperm was higher than that of goat sperm (58.52%) after cryopreservation ( < 0.01). Sperm motility was positively correlated with the activity of the two acrosome enzymes before and after cryopreservation ( < 0.01). Cryopreservation had a negative effect on acrosomal morphology, motility, and acrosomal enzyme activity in their sperm. The fertilization ability of ovine and goat sperm decreased significantly after cryopreservation, but that of frozen bovine sperm did not differ significantly when compared with fresh sperm. There was no significant difference between ovine and goat sperm indices, except for percentage of sperm with HYD activity.
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http://dx.doi.org/10.1590/1984-3143-ar2020-0219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159072PMC
March 2021

Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer.

Gut 2021 May 31. Epub 2021 May 31.

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Objective: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described.

Design: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and H3K9me3 for heterochromatin.

Results: We demonstrate that H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumour-specific enhancers for crucial oncogenes, such as and was required for excessive proliferation. Consistently, combination of MEK plus bromodomain inhibition was found to have synergistic effects in CRC patient-derived xenograft models. Probing intertumour heterogeneity, we identified four distinct enhancer subtypes (EPIgenome-based Classification, EpiC), three of which correlate well with previously defined transcriptomic subtypes (consensus molecular subtypes, CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, TGFβi, mTORi and SRCi) for EpiC groups.

Conclusion: Our data suggest that the dynamics of active enhancer underlies CRC progression and the patient-specific enhancer patterns can be leveraged for precision combination therapy.
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http://dx.doi.org/10.1136/gutjnl-2020-322835DOI Listing
May 2021

Projected changes in temperature, precipitation and potential evapotranspiration across Indus River Basin at 1.5-3.0 °C warming levels using CMIP6-GCMs.

Sci Total Environ 2021 May 20;789:147867. Epub 2021 May 20.

State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Institute for Disaster Risk Management, School of Geographical Science, Nanjing University of Information Science & Technology, Nanjing 210044, China. Electronic address:

The projections of mean temperature, precipitation (P), and potential evapotranspiration (PET) reflect the probabilities of long-term changes of hydrologic processes and induced extreme events. In this paper, we investigated the future changes in some pivotal climatic variables (mean temperature, precipitation, and potential evapotranspiration) under 1.5 °C, 2.0 °C, and 3.0 °C specific warming levels (SWLs) across the Indus River Basin of South Asia. The seven global climate models output under seven different emission scenarios (SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0, and SSP5-8.5) from the latest Sixth phase of Coupled Model Intercomparison Project (CMIP6) are used for this purpose. The Penman-Monteith approach is applied to estimate PET, and the water balance equation is for reflecting water surplus/deficit. Results indicate that except for precipitation, the greater increases in temperature and PET are inclined to happen with continued global warming. The highest increase in temperature is accounted for 14.6% (2.4 °C), and the enhanced PET is estimated at 5.2% higher than the reference period (1995-2014) under 3.0 °C SWL. While the precipitation is projected to increase by the highest 4.8% for 2.0 °C warming level. The differences in regional climate for an additional 0.5 °C (2.0-1.5 °C) and 1.0 °C (3.0-2.0 °C) of warming, the temperature is projected to increase by 0.4 °C and 0.9 °C in the entire IRB respectively. The highest increase in mean temperature (5.1%) and PET (2.4%) in the IRB are predicted to intensify for an additional 1.0 °C than that of 0.5 °C of warming, but precipitation is intended to decrease by 0.4%. Spatially, the increase in temperature, precipitation, and PET are dominated towards high elevation in the upper basin (north) under all the SWLs. The increased variability in climatological parameters across IRB depicts an evident occurrence of both wet events (upper basin) as well as dry events (lower basin) with the increase in global average temperature rise. However, these findings provide an insightful basis for water resource management as well as initiating mitigation and adaptation measures in the IRB related to water surplus (floods) and water deficit (droughts).
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http://dx.doi.org/10.1016/j.scitotenv.2021.147867DOI Listing
May 2021

GDI2 is a target of paclitaxel that affects tumorigenesis of prostate cancer via the p75NTR signaling pathway.

Biochem Biophys Res Commun 2021 May 26;562:119-126. Epub 2021 May 26.

Department of Biochemistry & Molecular Biology, Harbin Medical University, Harbin, China. Electronic address:

Background: Prostate cancer (PCa) refers to malignant tumors derived from prostate epithelial cells, whose morbidity and mortality rates have been increasing every year. Although new drugs for treating prostate cancer continue to emerge, the unclear mechanism underlying drug targets limits this therapy, thereby constraining identification of effective therapeutic targets. Although GDP dissociation inhibitor 2(GDI2) is highly expressed and closely associated with occurrence and development of many tumors, its role in prostate cancer remains unclear. In this study, we investigated the role of GDI2 and elucidated its underlying mechanism of action in prostate cancer. Moreover, we screened chemotherapeutic drugs that affect GDI2 expression with a view of identifying novel targets for diagnosis and treatment of prostate cancer.

Methods: We performed sequence analyses and functional assays to precisely elucidate the GDI2 role in prostate cancer. Moreover, we induced tumorigenesis in nude mice to verify the role of GDI2 in vivo. Finally, we used the CCK8 assay to ascertain the most suitable IC across the three drugs and performed quantitative real time polymerase chain reaction (qRT-PCR) and Western Blot to analyze the effects of drugs on expression of GDI2, p75NTR, and p-NFκB.

Results: GDI2 was up-regulated in prostate cancer cells and tissues. Knocking down GDI2 suppressed cell proliferation but promoted cell apoptosis. Interestingly, knocking down GDI2 activated the p75NTR signaling pathway, indicating, for the first time, that p75NTR is negatively correlated with GDI2 expression.

Conclusion: Taken together, these results indicate that GDI2 is a therapeutic target of paclitaxel. Knocking down of GDI2 inhibits cell proliferation and promotes cell apoptosis via the p75NTR signaling pathway in prostate cancer. Notably, paclitaxel inhibits GDI2 expression, implying that GDI2 may be a promising therapeutic target in prostate cancer.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.015DOI Listing
May 2021

Ag functionalized SnS with enhanced photothermal activity for safe and efficient wound disinfection.

Biomater Sci 2021 May 25. Epub 2021 May 25.

Institute of Physical Chemistry, College of Chemistry, Jilin University, Changchun 130012, P.R. China.

Severe bacterial infections have brought an urgent threat to our daily life, and photothermal therapy (PTT) has acted as an effective method to kill bacteria. Herein we decorated Ag on the surface of SnS2 ([email protected]), which has outstanding photothermal conversion capability and good biocompatibility. The decoration of Ag on SnS2 improved the absorption of near-infrared (NIR) light in comparison to SnS2, resulting in a temperature increase of 50 °C after 5 min of NIR light irradiation (1.9 W cm-2) and a photothermal conversion efficiency of 31.3%. [email protected] exhibits almost 100% growth inhibition of E. coli and S. aureus bacteria due to hyperthermia, with a concentration larger than 0.5 mg mL-1 and 5 min of NIR irradiation. Meanwhile, SEM images of treated bacterial cells showed the attachment of [email protected] on the cell surface and obvious cellular membrane destruction. [email protected] can also accelerate in vivo wound healing through PTT-induced bacterial disinfection. Therefore, [email protected] exhibits great potential for photothermal antibacterial application and wound disinfection.
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http://dx.doi.org/10.1039/d1bm00429hDOI Listing
May 2021

Correction to: Analgesic Effects of Navigated Repetitive Transcranial Magnetic Stimulation in Patients With Acute Central Poststroke Pain.

Pain Ther 2021 May 21. Epub 2021 May 21.

Department of Rehabilitation Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

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http://dx.doi.org/10.1007/s40122-021-00270-zDOI Listing
May 2021

sp. nov., isolated from marine sediment.

Int J Syst Evol Microbiol 2021 May;71(5)

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, PR China.

A Gram-stain negative, rod-shaped, facultatively aerobic, pale-beige-coloured bacterial strain, designated F7233, was isolated from coastal sediment sampled at Jingzi Bay, Weihai, PR China. Cells of strain F7233 were 0.3-0.4 µm wide, 1.2-1.4 µm wide long, non-spore-forming and motile with one flagellum. Optimum growth occurred at 30 °C, with 1.0 % (w/v) NaCl and at pH 6.5-7.0. Positive for nitrate reduction, hydrolysis of Tweens and oxidase activity. The sole respiratory quinone of strain F7233 was ubiquinone-10 and the predominant cellular fatty acid was summed feature 8 (C7/C6). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and one unidentified aminophospholipid. The G+C content of the chromosomal DNA was 63.3 mol%. Phylogenetic analysis of the 16S rRNA gene sequence revealed that the newly isolate belonged to the genus , with 96.8 % sequence similarity to MCCC 1A01226, 96.1 % similarity to JCM 20692 and 95.5% similarity to CC-SPIO-10-1. On the basis of phylogenetic, phenotypic and chemotaxonomic data, it is considered that strain F7233 should represent a novel species within the genus , for which the name sp. nov. is proposed. The type strain is F7233 (=MCCC 1H00419=KCTC 72859).
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http://dx.doi.org/10.1099/ijsem.0.004807DOI Listing
May 2021

Salegentibacter maritimus sp. nov., isolated from marine coastal sediment.

Syst Appl Microbiol 2021 May 5;44(3):126209. Epub 2021 May 5.

Marine College, Shandong University, Weihai, Shandong 264209, PR China; State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, PR China. Electronic address:

Two bacterial strains were isolated from a marine sediment sample taken from Jingzi Wharf, Weihai, China. These two strains were characterized at the phenotypic, chemotaxonomic, and genomic level. The two strains possessed almost identical 16S rRNA gene sequences (99.9 %). However, RAPD-PCR fingerprint patterns discriminated that they were not from one clonal origin. The average nucleotide identity (ANI) value and the digital DNA-DNA hybridization (dDDH) value between the two strains were 98.3 % and 85.4 %, respectively, suggestingthat they belonged to the same species. On the basis of the result of phylogenetic analysis of the 16S rRNA gene sequences, the two strains belonged to the genus Salegentibacter and were closely related to S. holothuriorum KCTC 12371 (98.6 %) and S. salegens DSM 5424 (98.2-98.3 %). The ANI and dDDH clearly separated strains F63223 and F60176 from the the most related type strains with values below the thresholds for species. The genome sizes of strains F63223 and F60176 were approximate 3.89 and 3.59 Mbp, respectively. The strain F63223 had 3,335 predicted genes with DNA G + C content of 35.6 %. The major respiratory quinone was MK-6 and the major polar lipids were phosphatidylethanolamine and one unidentified lipid. According to the results of the phenotypic, chemotaxonomic characterization, phylogenetic classification and genome analysis, the two isolates could be considered to represent a novel species of the genus Salegentibacter, for which the name Salegentibacter maritimus sp. nov., is proposed, with F63223 (=MCCC 1H00433 = KCTC 82417) as the type strain.
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http://dx.doi.org/10.1016/j.syapm.2021.126209DOI Listing
May 2021

Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through ATR upregulation.

Ecotoxicol Environ Saf 2021 Aug 12;219:112314. Epub 2021 May 12.

Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China. Electronic address:

PM infiltrates into circulation and increases the risk of systemic vascular dysfunction. As the first-line barrier against external stimuli, the molecular mechanism of the biological response of vascular endothelial cells to PM exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou 'real' airborne PM for 2 months and were found to display bronchial and alveolar damage. Importantly, in the present study, we have demonstrated that Cdk5 deficit induced peripheral vasoconstriction through angiotensin II type 1 receptor under angiotensin II stimulation in Cdh5-cre;Cdk5 mice. In the brain, Cdk5 deficit increased the myogenic activity in the medullary arterioles under external pressure. On the other hand, no changes in cerebral blood flow and behavior patterns were observed in the Cdh5-cre;Cdk5 mice exposed to PM. Therefore, our current findings indicate that CDK5 plays an important role in endothelium cell growth, migration, and molecular transduction, which is also a sensor for the response of vascular endothelial cells to PM.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112314DOI Listing
August 2021

Role of D-alanylation of Streptococcus mutans lipoteichoic acid in interspecies competitiveness.

Mol Oral Microbiol 2021 May 12. Epub 2021 May 12.

Fujian Key Laboratory of Oral Diseases &, Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.

Background: The D-alanylation of lipoteichoic acid (LTA) is essential for the physiological metabolism of Streptococcus mutans (S. mutans). This study was designed to investigate the influence of D-alanylation of LTA on interspecies competitiveness of S. mutans.

Methods: The process of D-alanylation was blocked by the inactivation of dltC. Agar competition assays, conditioned medium assays, and qRT-PCR were used to evaluate the production of antimicrobial compounds in S. mutans mutant. Dual-species biofilm was formed to investigate the competitiveness of S. mutans mutant cocultured with S. sanguinis or S. gordonii.

Results: S. mutans mutant could not produce antimicrobial compounds efficiently when cocultured with commensal bacteria (*p < 0.05). The mutant showed compromised competitiveness in dual-species biofilms. The ratio of the mutant in dual-species biofilms decreased, and the terminal pH of the culture medium in mutant groups (mutant+S. sanguinis/S. gordonii) was higher than that in wild-type groups (*p < 0.05). Scanning electron microscope (SEM) showed weaker demineralization of enamel treated with dual-species biofilms consisting of mutant and commensal bacteria.

Conclusion: D-Alanylation is involved in interspecies competitiveness of S. mutans within oral biofilm by regulating mutacins and lactic acid production, which may modulate the profiles of dental biofilms. Results provide new insights into dental caries prevention and treatment.
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http://dx.doi.org/10.1111/omi.12344DOI Listing
May 2021

The different hypoglycemic effects between East Asian and non-Asian type 2 diabetes patients when treated with SGLT-2 inhibitors as an add-on treatment for metformin: a systematic review and meta-analysis of randomized controlled trials.

Aging (Albany NY) 2021 05 11;13(9):12748-12765. Epub 2021 May 11.

Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Ji-nan, Shandong 250014, China.

Aims: To investigate the efficacy and safety of SGLT-2 inhibitors as an add-on treatment for metformin between Asian and non-Asian T2DM.

Methods: A systematic literature search of PubMed, EMBASE, and the Cochrane Library was performed through August 2020 with the following keywords: Sodium-Glucose Transporter 2 Inhibitors, Sodium Glucose Transporter 2 Inhibitors, SGLT2 inhibitor, SGLT-2 inhibitors, type 2 diabetes, and randomized controlled trials. Double-blinded RCTs comparing SGLT-2 inhibitors as an add-on treatment for metformin and metformin monotherapy in adults with type 2 diabetes were included. A random effects model was used to calculate overall effect sizes.

Results: 5 RCTs with 1193 Asian patients and 7 RCTs with 2098 non-Asian patients were investigated. The improvement in HbA1c and fasting blood glucose in the Asian patients (WMD, -0.73%; 95% CI, -1.01% to -0.46%, < 0.01; WMD, -1.51; 95% CI, -1.81 to -1.21, < 0.01, respectively) were both significantly better than in the non-Asians (WMD, -0.45%; 95% CI, -0.62% to -0.29%, < 0.01; WMD, -1.03; 95% CI, -1.27 to -0.78, < 0.01, respectively). The effect of weight loss was similar in the non-Asian patients and Asian patients. There was little difference in the improvement of systolic blood pressure between them. The risk of serious adverse events was not significantly increased between the Asian and non-Asian patients.

Conclusion: SGLT-2 inhibitors as an add-on treatment for metformin are more efficacious in East Asian T2DM patients than in non-Asian T2DM patients without an additional risk of severe adverse events.
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http://dx.doi.org/10.18632/aging.202945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148508PMC
May 2021

Clinical and pathological analysis of renal biopsies of elderly patients in Northeast China: a single-center study.

Ren Fail 2021 Dec;43(1):851-859

The Department of Nephropathy, The Second Hospital of Jilin University, Changchun, China.

Purpose: To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China.

Methods: We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age: below 60 years (non-elderly group,  = 5923) and at least 60 years (elderly group,  = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the -test and chi-square test.

Results: Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders ( < .05). The incidence of IgA nephropathy, mesangial proliferative glomerulonephritis, and lupus nephritis was significantly lower in elderly patients than in non-elderly patients. The incidence of membranous nephropathy, membranoproliferative glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, systemic vasculitis-associated renal damage, and amyloid nephropathy was significantly higher in elderly patients than in non-elderly patients ( < .05). The incidence of perinephric hematoma (≥4 cm) in elderly patients with renal biopsy was lower than that in non-elderly patients. We noted that 79.9% of primary glomerulonephritis patients who received immunosuppressive therapy showed a remission rate of 83.5%.

Conclusion: The spectrum of kidney disease in the elderly is different from that in the younger population.
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http://dx.doi.org/10.1080/0886022X.2021.1923527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118502PMC
December 2021

Acculturation Stress, Satisfaction, and Frustration of Basic Psychological Needs and Mental Health of Chinese Migrant Children: Perspective from Basic Psychological Needs Theory.

Int J Environ Res Public Health 2021 04 29;18(9). Epub 2021 Apr 29.

Department of Sociology, Zhejiang University, Hangzhou 310058, China.

Acculturation stress is prevalent among migrant populations. The current study examines whether acculturation stress influences migrant children's mental health through the mediators of the satisfaction and frustration of basic psychological needs for autonomy, relatedness, and competence. A sample of 484 migrant children is obtained in Kunming, China using a multi-stage cluster random sampling. Data are analyzed through structural equation modeling in Mplus 8.0. Results indicate that acculturation stress has a direct impact on children's depression but no significant direct effect on children's happiness. Acculturation stress also has indirect effects on depression and happiness via the mediators of need satisfaction and frustration. Acculturation stress is negatively associated with need satisfaction and positively associated with need frustration, which is further significantly predictive of children's happiness and depression. Overall, this study validates the basic psychological needs theory in the context of China's internal migration. Findings contribute to the understanding of the mechanisms that underlie the relationship between acculturation stress and psychological outcomes and provide practical implications for future interventions.
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http://dx.doi.org/10.3390/ijerph18094751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124301PMC
April 2021

Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors.

Stem Cell Res Ther 2021 May 3;12(1):266. Epub 2021 May 3.

Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Objectives: Recently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy.

Materials And Methods: The expression level of endothelial-specific genes and proteins after chemical induction of SCAP was assessed by RT-PCR, western blotting, flow cytometry and immunofluorescence. The in vitro functions of SCAP-derived chemical-induced endothelial cells (SCAP-ECs) were evaluated by tube-like structure formation assay, acetylated low-density lipoprotein (ac-LDL) uptake and NO secretion detection. The proliferation and the migration ability of SCAP-ECs were evaluated by CCK-8 and Transwell assay. LPS stimulation was used to mimic the inflammatory environment in demonstrating the ability of SCAP-ECs to express adhesion molecules. The in vivo Matrigel plug angiogenesis assay was performed to assess the function of SCAP-ECs in generating vascular structures using the immune-deficient mouse model.

Results: SCAP-ECs expressed upregulated endothelial-specific genes and proteins; displayed endothelial transcriptional networks; exhibited the ability to form functional tubular-like structures, uptake ac-LDL and secrete NO in vitro; and contributed to generate blood vessels in vivo. The SCAP-ECs could also express adhesion molecules in the pro-inflammatory environment and have a similar migration and proliferation ability as HUVECs.

Conclusions: Our study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of SCAP, which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases.
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http://dx.doi.org/10.1186/s13287-021-02350-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091697PMC
May 2021

Value of the diving method for capsule endoscopy in the examination of small-intestinal disease: a prospective randomized controlled trial.

Gastrointest Endosc 2021 Apr 28. Epub 2021 Apr 28.

Department of Gastroenterology, West China Hospital, Sichuan University, China. Electronic address:

Background And Aims: Video capsule endoscopy (VCE) is limited by poor image quality and incomplete small-bowel transit. This study was designed to evaluate the diving method for VCE in the examination of small-intestinal disease.

Methods: From July 2017 to September 2017, eligible patients were randomly assigned into 2 groups (the diving group and the control group). For the diving group, 500 mL of water was administered every hour when the capsule reached the small bowel. The primary outcomes were image quality and positive findings. Secondary outcomes included the completion rate of examination, gastric transit time (GTT), small-bowel transit time (SBTT), lesion detection rate, adverse events, and patient's satisfaction.

Results: A total of 140 patients were included. The scores of endoscopic images in the proximal third and middle third of the small bowel in the diving group were significantly higher than that in the control group (3.47 ± 0.60 vs 3.11 ± 0.63, P = 0.007; 3.24 ± 0.59 vs 2.78 ± 0.74, P = 0.002, respectively). The positive findings in the distal third of the small bowel were significantly different between 2 groups (P = 0.005). The completion rate in the diving group was significantly higher (92.19% vs 76.32%, P = 0.012). The GTT, SBTT, and lesion detection rate was similar in 2 groups (P = 0.282, 0.067, and 0.577, respectively).

Conclusion: The diving method for VCE examination effectively improves the endoscopic view in the proximal and middle thirds of the small bowel, as well as the positive findings in distal small intestine, and increases the completion rate.
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http://dx.doi.org/10.1016/j.gie.2021.04.018DOI Listing
April 2021

Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions.

Int J Mol Sci 2021 Apr 16;22(8). Epub 2021 Apr 16.

Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions.
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http://dx.doi.org/10.3390/ijms22084120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073638PMC
April 2021

Using logic regression to characterize extreme heat exposures and their health associations: a time-series study of emergency department visits in Atlanta.

BMC Med Res Methodol 2021 Apr 26;21(1):87. Epub 2021 Apr 26.

Department of Biostatistics and Bioinformatics, Emory University, Atlanta, USA.

Background: Short-term associations between extreme heat events and adverse health outcomes are well-established in epidemiologic studies. However, the use of different exposure definitions across studies has limited our understanding of extreme heat characteristics that are most important for specific health outcomes or subpopulations.

Methods: Logic regression is a statistical learning method for constructing decision trees based on Boolean combinations of binary predictors. We describe how logic regression can be utilized as a data-driven approach to identify extreme heat exposure definitions using health outcome data. We evaluated the performance of the proposed algorithm in a simulation study, as well as in a 20-year time-series analysis of extreme heat and emergency department visits for 12 outcomes in the Atlanta metropolitan area.

Results: For the Atlanta case study, our novel application of logic regression identified extreme heat exposure definitions that were associated with several heat-sensitive disease outcomes (e.g., fluid and electrolyte imbalance, renal diseases, ischemic stroke, and hypertension). Exposures were often characterized by extreme apparent minimum temperature or maximum temperature over multiple days. The simulation study also demonstrated that logic regression can successfully identify exposures of different lags and duration structures when statistical power is sufficient.

Conclusion: Logic regression is a useful tool for identifying important characteristics of extreme heat exposures for adverse health outcomes, which may help improve future heat warning systems and response plans.
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http://dx.doi.org/10.1186/s12874-021-01278-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077733PMC
April 2021

PDCD4-mediated downregulation of burden in macrophages.

Cent Eur J Immunol 2021 18;46(1):38-46. Epub 2021 Apr 18.

Institute for Advanced Study, Shenzhen University, Shenzhen, China.

Introduction: Macrophages are effector cells of the innate immune system and defend against invading pathogens. Previous reports have shown that infection with Listeria monocytogenes upregulates miR-21a expression in macrophages.

Aim Of The Study: We aimed to verify whether programmed cell death 4 (PDCD4) is involved in the high bacterial burden observed in macrophages during late-stage L. monocytogenes infections.

Material And Methods: We examined the expression of miR-21a and its known target PDCD4 in macrophages after L. monocytogenes infection. The macrophages' uptake ability of L. monocytogenes was measured using FluoSpheres Carboxylate-modified microspheres. We depleted PDCD4 by transfecting macrophages with siPDCD4.

Results: In macrophages, PDCD4 protein was downregulated 5 h, but not 2 h, after L. monocytogenes infection. Our results validated the hypothesis that PDCD4-depleted macrophages present a higher L. monocytogenes burden. Moreover, we found that the activation of c-Jun and STAT3 accompanied PDCD4 downregulation.

Conclusions: Our results showed that PDCD4 mediated the suppression of L. monocytogenes infection in macrophages via c-Jun/STAT3 signalling activation.
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http://dx.doi.org/10.5114/ceji.2021.105244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056355PMC
April 2021

Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.

Nat Commun 2021 04 23;12(1):2421. Epub 2021 Apr 23.

Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.

The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules.
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http://dx.doi.org/10.1038/s41467-021-22624-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065162PMC
April 2021

Analgesic Effects of Navigated Repetitive Transcranial Magnetic Stimulation in Patients With Acute Central Poststroke Pain.

Pain Ther 2021 Apr 17. Epub 2021 Apr 17.

Department of Rehabilitation Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Introduction: Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke.

Methods: We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks.

Results: Significant treatment-time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P < 0.001, Cohen's d = 1.302) (P = 0.003, Cohen's d = 0.771), and this effect lasted until the third week (P = 0.001, Cohen's d = 0.860) (P = 0.027, Cohen's d = 0.550). The HAM-A and HAM-D scores did not change in the rTMS group when compared with the sham group (P = 0.341, Cohen's d = 0.224) (P = 0.356, Cohen's d = 0.217). The serum BDNF levels were significantly higher in the treated group (P = 0.048, Cohen's d = -0.487), and the resting motor threshold (RMT) decreased by 163.65%.

Conclusion: Our findings indicate that rTMS applied over the upper extremity area of the motor cortex can effectively alleviate acute CPSP, possibly by influencing cortical excitability and serum BDNF secretion.

Trial Registration: This trial is registered with Clinical Trial Registry of China: Reg. No. ChiCTR-INR-17012880.
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http://dx.doi.org/10.1007/s40122-021-00261-0DOI Listing
April 2021

Economic evaluation of remdesivir for the treatment of severe COVID-19 patients in China under different scenarios.

Br J Clin Pharmacol 2021 Apr 14. Epub 2021 Apr 14.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Aims: The present study aimed to evaluate the cost-effectiveness of the 5-day remdesivir regimen compared with standard of care among severe COVID-19 patients in China, the evidence on which is essential to inform the necessity of securing access to remdesivir.

Methods: A dynamic transmission model that extended the susceptible-exposed-infected-recovered framework by incorporating asymptomatic, presymptomatic and waiting-to-be-diagnosed patients was constructed to conduct the cost-effectiveness analysis from the healthcare system perspective. To estimate epidemic parameters, the model was first calibrated to the observed epidemic curve in Wuhan from 23 January to 19 March 2020. Following the calibration, the infected compartment was replaced by 3 severity-defined health states to reflect differential costs and quality of life associated with disease gravity. Costs and quality-adjusted life year (QALY) outcomes of 9 million simulated people were accrued across time to evaluate the incremental cost-effectiveness ratio of remdesivir. As robustness checks, an alternative modelling technique using decision tree, additional epidemic scenarios representing different epidemic intensities, and 1-way parameter variations were also analysed.

Results: Remdesivir treatment cost CN¥97.93 million more than standard of care. Also, the net QALY gain from 5-day remdesivir treatment was 6947 QALYs. As such, the incremental cost-effectiveness ratio was CN¥14 098/QALY, substantially lower than the gross domestic product per capita threshold. The peak daily number of severe cases was 19% lower in the remdesivir treatment strategy. Overall, results were robust in alternative scenarios and sensitivity analyses.

Conclusion: Given the cost-effectiveness profile, access to remdesivir for severe COVID-19 patients in China should be considered.
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http://dx.doi.org/10.1111/bcp.14860DOI Listing
April 2021

Small molecules efficiently reprogram apical papilla stem cells into neuron-like cells.

Exp Ther Med 2021 Jun 24;21(6):546. Epub 2021 Mar 24.

Restorative Dental Sciences, Endodontology, Faculty of Dentistry, The University of Hong Kong, Hong Kong 999077, SAR, P.R. China.

Stem cell-based therapy may provide a novel approach for neural tissue regeneration. A small molecule cocktail-based culture protocol was previously shown to enhance neurogenic differentiation of stem cells from dental tissues. The present study aimed to investigate the early phase of small molecule-induced neurogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were cultured in neural-induction medium or neural-induction medium with small molecules (NIMS-SCAP) and examined for their cell morphologies. Expression levels of neural progenitor cell-related markers, including Nestin, paired-box gene 6 (Pax6) and Sry-related HMG box 2 (Sox2), were examined using western blotting and immunocytofluorescence. Expression of differentiated neuron-related markers, including neurofilament protein (NFM), neuron-specific nuclear protein (NeuN) and microtubule-associated protein (MAP)-2, were also examined using western blotting, while NFM and MAP2 gene expression and cell proliferation were assessed using reverse transcription-quantitative (RT-q)PCR and Cell Counting Kit (CCK)-8 assays, respectively. SCAP morphology was affected by small molecules after as little as 30 min. Specifically, Nestin, Pax6 and Sox2 expression detected using western blotting was increased by day 3 but then decreased over the course of 7 days with neural induction, while immunocytofluorescence revealed expression of all three markers in NIMS-SCAP. The protein levels of NFM, NeuN and MAP2 on day 7 were significantly upregulated in NIMS-SCAP, as detected using western blotting, while NFM and MAP2 gene expression levels detected using RT-qPCR were significantly increased on days 5 and 7. Proliferation of NIMS-SCAP ceased after 5 days. Electrophysiological analysis showed that only SCAP cultured in NIMS had the functional activity of neuronal cells. Thus, small molecules reprogrammed SCAP into neural progenitor cells within the first 3 days, followed by further differentiation into neuron-like cells.
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http://dx.doi.org/10.3892/etm.2021.9978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027758PMC
June 2021

Human milk cholesterol is associated with lactation stage and maternal plasma cholesterol in Chinese populations.

Pediatr Res 2021 Apr 12. Epub 2021 Apr 12.

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Milk cholesterol concentrations throughout lactation were analyzed, and the relationship between maternal plasma cholesterol and milk cholesterol in various Chinese populations was examined.

Methods: A sub-sample of 1138 lactating women was randomly selected from a large cross-sectional study in China (n = 6481). Milk cholesterol concentrations were determined by HPLC, and concentrations of maternal plasma lipids were determined by an automated biochemical analyzer.

Results: The mean cholesterol concentrations were 200, 171, and 126 mg/L for colostrum, transitional milk, and mature milk, respectively. Cholesterol concentrations differed significantly between stages of lactation (colostrum vs. transitional milk, colostrum vs. mature milk, transitional milk vs. mature milk, all p < 0.001). Concentrations of maternal plasma total cholesterol (TC) (p = 0.02) and low-density lipoprotein cholesterol (LDL-C) (p = 0.03) were significantly associated with milk cholesterol. Milk cholesterol concentrations varied among different ethnicities (Tibetan vs. Hui: 164 vs. 131 mg/L, p = 0.027) but not among different geographic regions.

Conclusions: The concentration of cholesterol in human milk changes dynamically throughout lactation. Milk cholesterol concentrations are significantly associated with maternal plasma concentrations of TC and LDL-C, and milk cholesterol concentrations vary across ethnicities in China.

Impact: Concentrations of milk cholesterol were measured in various Chinese populations. Cholesterol concentrations differ significantly between stages of lactation. Maternal plasma total cholesterol and low-density lipoprotein cholesterol are associated with milk cholesterol. Milk cholesterol concentrations vary across ethnicities in China.
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http://dx.doi.org/10.1038/s41390-021-01440-7DOI Listing
April 2021

High phosphate impairs arterial endothelial function through AMPK-related pathways in mouse resistance arteries.

Acta Physiol (Oxf) 2021 04 20;231(4):e13595. Epub 2020 Dec 20.

Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.

Aims: In patients with renal disease, high serum phosphate shows a relationship with cardiovascular risk. We speculate that high phosphate (HP) impairs arterial vasodilation via the endothelium and explore potential underlying mechanisms.

Methods: Isolated vessel relaxation, endothelial function, glomerular filtration rate (GFR), oxidative stress status and protein expression were assessed in HP diet mice. Mitochondrial function and protein expression were assessed in HP-treated human umbilical vein endothelial cells (HUVECs).

Results: High phosphate (1.3%) diet for 12 weeks impaired endothelium-dependent relaxation in mesenteric arteries, kidney interlobar arteries and afferent arterioles; reduced GFR and the blood pressure responses to acute administration of acetylcholine. The PPARα/LKB1/AMPK/eNOS pathway was attenuated in the endothelium of mesenteric arteries from HP diet mice. The observed vasodilatory impairment of mesenteric arteries was ameliorated by PPARα agonist WY-14643. The phosphate transporter PiT-1 knockdown prevented HP-mediated suppression of eNOS activity by impeding phosphorus influx in HUVECs. Endothelium cytoplasmic and mitochondrial reactive oxygen species (ROS) were increased in HP diet mice. Moreover HP decreased the expression of mitochondrial-related antioxidant genes. Finally, mitochondrial membrane potential and PGC-1α expression were reduced by HP treatment in HUVECs, which was partly restored by AMPKα agonist.

Conclusions: HP impairs endothelial function by reducing NO bioavailability via decreasing eNOS activity and increasing mitochondrial ROS, in which the AMPK-related signalling pathways may play a key role.
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http://dx.doi.org/10.1111/apha.13595DOI Listing
April 2021

An improved biolistic delivery and analysis method for evaluation of DNA and CRISPR-Cas delivery efficacy in plant tissue.

Sci Rep 2021 Apr 8;11(1):7695. Epub 2021 Apr 8.

Department of Materials Science and Engineering, Iowa State University, Ames, IA, USA.

Biolistic delivery is widely used for genetic transformation but inconsistency between bombardment samples for transient gene expression analysis often hinders quantitative analyses. We developed a methodology to improve the consistency of biolistic delivery results by using a double-barrel device and a cell counting software. The double-barrel device enables a strategy of incorporating an internal control into each sample, which significantly decreases variance of the results. The cell counting software further reduces errors and increases throughput. The utility of this new platform is demonstrated by optimizing conditions for delivering DNA using the commercial transfection reagent TransIT-2020. In addition, the same approach is applied to test the efficacy of multiple gRNAs for CRISPR-Cas9-mediated gene editing. The novel combination of the bombardment device and analysis method allows simultaneous comparison and optimization of parameters in the biolistic delivery. The platform developed here can be broadly applied to any target samples using biolistics, including animal cells and tissues.
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http://dx.doi.org/10.1038/s41598-021-86549-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032657PMC
April 2021

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

J Urol 2021 Apr 5:101097JU0000000000001767. Epub 2021 Apr 5.

Carolina Urologic Research Center, Myrtle Beach, South Carolina.

Purpose: No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons.

Materials And Methods: Individual patient data from the phase III ARAMIS trial (N=553; N=943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (N=401; N=806) and PROSPER (N=468; N=933) trials. Only baseline factors consistently reported across trials were included as matching covariates. Both indirect comparisons matched on age, prostate specific antigen level and doubling time, Eastern Cooperative Oncology Group performance status, Gleason score, and bone-sparing agent use. Darolutamide vs apalutamide also matched on prior surgery and darolutamide vs enzalutamide also matched on region. Risk differences and odds ratios were calculated for adverse events and hazard ratios for metastasis-free survival.

Results: No differences in metastasis-free survival hazard ratios were found after matching in either comparison. However, fall, fracture and rash rates were statistically significantly lower in favor of darolutamide vs apalutamide. Fall, dizziness, mental impairment, fatigue and severe fatigue rates were statistically significantly lower in favor of darolutamide vs enzalutamide.

Conclusions: While metastasis-free survival did not differ across drugs in these cross-trial indirect comparisons, darolutamide showed a favorable safety and tolerability profile in prespecified adverse events vs apalutamide and enzalutamide. Consideration of these adverse events is important in clinical decision-making and treatment selection in nonmetastatic castration-resistant prostate cancer.
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http://dx.doi.org/10.1097/JU.0000000000001767DOI Listing
April 2021

Phototherapy together with it triggered immunological response for Anti-HPV treatment of oropharyngeal cancer: Removing tumor and pathogenic virus simultaneously.

Biomaterials 2021 05 25;272:120777. Epub 2021 Mar 25.

Harbin Medical University Cancer Hospital, Harbin, 150080, China. Electronic address:

Oropharyngeal squamous cell carcinoma (OPSCC) is one of most common cancers that often brings lots of inconvenience to the patient in swallowing and phonation even after the operation. Moreover, OPSCC is typically as nodal metastases and high recurrence rate due to the high-risk human papillomavirus (HPV) infection for 90% of patients. Obviously, completely curing OPSCC requires simultaneous removal of solid tumor and related pathogenic virus, which is very indispensable but never be realized by any kind of clinical therapy up to now. In this work, we selected the ZrC nanoparticles as difunctional photoactive substance for synchronous generation of hyperthermia and reactive oxygen species (ROS) under NIR excitation. The resultant synergistic photothermal and photodynamic treatment outcome contributed to an excellent anti-tumor effect. The phototherapy of this work was found not only to be able to damage cancer cells directly, but also could trigger the host immunity for further tumor removal and desirable HPV inactivation. An immunologic mechanism of this work was reasonable proposed by monitoring level of shock protein (HSP), calreticulin (CRT), T lymphocytes and dendritic cells (DCs) and immune check point of B7H3, B7H4 and PD-L1 post phototherapy. It was found that tumor-associated antigens of CRT ("eat-me" signal), HSPs and cell debris were released as cancer cell damage, and then the adaptive immune system and the congenital immunity were triggered to activate DCs maturity, antigen presentation to T cells, proliferation of CD4 and CD8 T cells, recruiting macrophages and NK cells and so forth immune responses. Being the first example of using phototherapy for virus-related cancer study, this work opens the door for photo-immunotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120777DOI Listing
May 2021

Method for exposure dose monitoring and control in scanning beam interference lithography.

Appl Opt 2021 Apr;60(10):2767-2774

To improve grating manufacturing process controllability in scanning beam interference lithography (SBIL), a novel method for exposure dose monitoring and control is proposed. Several zones in a narrow monitoring region are fabricated on a grating substrate by piecewise uniform scanning. Two monitoring modes are given based on the different widths of the monitoring region. The monitoring curve of the latent image diffraction efficiency to scanning velocity is calculated by rigorous coupled wave analysis. The calculation results show that the exposure dose in SBIL can be monitored by the shape change of the monitoring curve, and an optimized scanning velocity can be selected in the monitoring curve to control the exposure dose.
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http://dx.doi.org/10.1364/AO.420870DOI Listing
April 2021