Publications by authors named "Xiaodong Zhang"

1,260 Publications

  • Page 1 of 1

Small vs. Large Unruptured Cerebral Aneurysm: Concerns With the Age of Patient.

Front Neurol 2021 21;12:735456. Epub 2021 Sep 21.

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The coiling and clipping of unruptured cerebral aneurysms (UCAs) in older patients has increased rapidly, and aneurysm size was a significant factor for decision-making in the treatment of UCAs. The purpose of the study was to investigate the impact of age on the functional outcomes of patients between the small versus large UCAs. We conducted a retrospective study for consecutive cases of UCAs admitted from May 2011 to December 2020. According to the maximum diameter of UCA, patients were divided into small UCAs (≤ 5 mm) group and large UCAs (>5 mm) group. Baseline characteristics, clinical complications, and outcomes of patients between the two groups were analyzed. A total of 564 UCA patients received preventive treatment, including 165 small UCAs and 399 large UCAs. Compared with the small UCA group, the incidence of ischemia event in the large UCA group was significantly higher (7.3 vs. 2.4%; = 0.029). Multivariable analysis demonstrating age ( = 0.006) and treatment modality ( < 0.001) were independent risk factors associated with poor outcome for patients with large UCAs. Preventive treatment of small UCAs is safe and effective, but older patients with large UCAs are at high risk of poor outcome, and the operations should be more cautious.
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http://dx.doi.org/10.3389/fneur.2021.735456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490624PMC
September 2021

Thiolate-Assisted Route for Constructing Chalcogen Quantum Dots with Photoinduced Fluorescence Enhancement.

ACS Appl Mater Interfaces 2021 Oct 7. Epub 2021 Oct 7.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.

Despite great efforts in the development of diverse nanomaterials, a general route to synthesize metal-free chalcogen quantum dots (QDs) is still lacking. Moreover, the modification of chalcogen QDs is a bottleneck that severely hinders their applications. Herein, we develop a facile method to construct different chalcogen QDs (including S QDs, Se QDs, and Te QDs) with the assistance of thiolates. In addition to stabilizing chalcogen QDs, the thiolates also endow the chalcogen QDs with favorable modifiability. Different from most dyes whose fluorescence is quenched after short-term light irradiation, the prepared chalcogen QDs have significantly enhanced fluorescence emission under continuous light irradiation. Taking advantage of the distinctive photoinduced fluorescence enhancement property, long-time cell imaging with superb performance is realized using the chalcogen QDs. It is envisioned that the chalcogen QDs show promising potential as fluorescent materials in different fields beyond bioimaging.
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http://dx.doi.org/10.1021/acsami.1c15772DOI Listing
October 2021

Deriving the angular response function for backscattering sensors.

Appl Opt 2021 Oct;60(28):8676-8687

We derived the angular response function () for scattering sensors that automatically satisfies the normalization criterion and its corresponding weight (). 's, derived for two commercial sensors, HydroScat-6 (HOBI Labs) and ECO-BB (Sea-Bird Inc.), agrees well with the Monte Carlo simulation and direct measurements. The backscattering measured for microbeads of known sizes agrees better with Mie calculation when the derived was applied. We deduced that the reduction of with increasing attenuation coefficient is related to path length attenuation and showed that this theoretically derived correction factor performs better than the default methods for the two commercial backscattering sensors. The analysis conducted in this study also leads to an estimate of uncertainty budget for the two sensors. The major uncertainty for ECO-BB is associated with its angular response function because of its wide field of view, whereas the main uncertainty for the HydrScat-6 is due to attenuation correction because of its relatively long path length.
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http://dx.doi.org/10.1364/AO.437735DOI Listing
October 2021

Quantitative evaluation of bone marrow fat content and unsaturated fatty index in young male soccer players using proton magnetic resonance spectroscopy (H-MRS): a preliminary study.

Quant Imaging Med Surg 2021 Oct;11(10):4275-4286

Department of Medical Imaging, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou, China.

Background: Marrow fat exists as a distinct adipose tissue and plays a critical role in affecting both the quantity and quality of bone. However, the effect of soccer training on marrow fat has been rarely reported. This study aims to evaluate and characterize the marrow fat content and composition in different bone areas of soccer players and age-matched healthy subjects using proton magnetic resonance spectroscopy (H-MRS).

Methods: Between May 2020 and June 2020, 20 professional soccer players (20.7±0.9 years) and 20 age-matched healthy subjects (21.2±0.8 years) were enrolled in this cross-sectional study. The H-MRS were acquired from the 3 lumbar vertebrae, bilateral femoral necks, and distal tibias of all subjects using a single-voxel point-resolved spatially localized spectroscopy (PRESS) sequence. Four soccer players underwent a second magnetic resonance (MR) examination within a 30-minute interval after the initial scan to evaluate test-retest reproducibility. Inter- and intra-observer measurement reliabilities were assessed using 10 randomly selected spectra from the soccer players group. All spectra were processed using the jMRUI software package (http://www.jmrui.eu/). Quantified water and lipid signals were used to calculate fat content (FC) and the unsaturated fatty index (UI).

Results: Compared with healthy subjects, we found that soccer players had a lower FC in L3 and bilateral femoral necks and higher UI in the left femoral neck (P<0.05). All FC and UI values of the bilateral distal tibias showed no significant differences between the two groups (P>0.05). The UI values of the right femoral neck or distal tibia were markedly higher than the left side in both inactive subjects and soccer players (P<0.05, except for the femoral neck in players), and there were notable ΔUI differences in the lower limbs between the soccer players and the healthy subjects (P<0.05).

Conclusions: Soccer practice can be considered a positive sport that contributes to decreasing FC in lumbar vertebrae and femoral necks and increasing the UI in femoral necks. Quantitative MRS provides an ideal modality to predict marrow fat metabolism caused by mechanical stimulation.
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http://dx.doi.org/10.21037/qims-21-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408790PMC
October 2021

Missing-Linker-Assisted Artesunate Delivery by Metal-Organic Frameworks for Synergistic Cancer Treatment.

Angew Chem Int Ed Engl 2021 Sep 30. Epub 2021 Sep 30.

Nanyang Technological University, Division of Chemistry and Biological Chemistry, SINGAPORE.

Clinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of ATS nanomedicine through the self-assembly with Mn[Co(CN)6]2/3 1/3 metal-organic frameworks (MOFs) having hidden missing linkers. The defects originated from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co-loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3-, Mn2+ acts as an efficient catalyst to promote the bicarbonate-activated H2O2 system and induce oxidative death to cancer cells based on ATS with an endoperoxide bridge. The released [CoIII(CN)6] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect-engineered MOFs with hidden missing linkers hold great promises in advancing the practical uses of ATS as an antitumor medicine.
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http://dx.doi.org/10.1002/anie.202112128DOI Listing
September 2021

Dynamic Robustness of Open-Source Project Knowledge Collaborative Network Based on Opinion Leader Identification.

Entropy (Basel) 2021 Sep 21;23(9). Epub 2021 Sep 21.

School of Economics and Management, University of Science and Technology Beijing, Beijing 100083, China.

A large amount of semantic content is generated during designer collaboration in open-source projects (OSPs). Based on the characteristics of knowledge collaboration behavior in OSPs, we constructed a directed, weighted, semantic-based knowledge collaborative network. Four social network analysis indexes were created to identify the key opinion leader nodes in the network using the entropy weight and TOPSIS method. Further, three degradation modes were designed for (1) the collaborative behavior of opinion leaders, (2) main knowledge dissemination behavior, and (3) main knowledge contribution behavior. Regarding the degradation model of the collaborative behavior of opinion leaders, we considered the propagation characteristics of opinion leaders to other nodes, and we created a susceptible-infected-removed (SIR) propagation model of the influence of opinion leaders' behaviors. Finally, based on empirical data from the Local Motors open-source vehicle design community, a dynamic robustness analysis experiment was carried out. The results showed that the robustness of our constructed network varied for different degradation modes: the degradation of the opinion leaders' collaborative behavior had the lowest robustness; this was followed by the main knowledge dissemination behavior and the main knowledge contribution behavior; the degradation of random behavior had the highest robustness. Our method revealed the influence of the degradation of collaborative behavior of different types of nodes on the robustness of the network. This could be used to formulate the management strategy of the open-source design community, thus promoting the stable development of OSPs.
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http://dx.doi.org/10.3390/e23091235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470236PMC
September 2021

Interferon-γ-Induced Myeloid-Derived Suppressor Cells Aggravate Kidney Ischemia-Reperfusion Injury by Regulating Innate Immune Cells.

Nephron 2021 Sep 21:1-11. Epub 2021 Sep 21.

Department of Urology, Capital Medical University Beijing Chaoyang Hospital, Beijing, China.

Objective: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cells which can suppress T-cell functionality. Herein, we evaluated the functional importance of MDSCs in the context of kidney ischemia-reperfusion injury (IRI) and explored their ability to regulate innate and adaptive immune cell function in this context.

Methods: The differentiation of MDSCs was induced in vitro by treating cells with GM-CSF and interferon (IFN)-γ. In a murine model of renal IRI, serum creatinine and blood urea nitrogen values were measured to monitor kidney function, while histopathological and immunohistochemical approaches were used to assess kidney injury severity. In addition, flow cytometry was employed to assess the phenotypes and apoptosis of kidney cells in these mice.

Results: MDSCs induced by treatment with GM-CSF + IFN-γ could suppress T-cell functionality in vitro. The adoptive transfer of these MDSCs into an IRI mouse model system enhanced kidney damage and impaired renal function following the recruitment of these cells to renal tissues in these mice. Following such adoptive transfer, the relative frequency of MDSCs with a CD11b+Ly6G-Ly6Chigh monocytic-MDSC phenotype decreased, whereas cells with a CD11b+Ly6G+Ly6Clow polymorphonuclear-MDSC phenotype become more prevalent within kidney tissues following IRI. Adoptive transfer also coincided with increased frequencies of macrophages and dendritic cells (DCs) in the kidney tissues. This suggested that M-MDSCs contributed to early-stage renal IRI damage by differentiating into these deleterious cell types. However, MDSC-induced suppression of CD4+ and CD8+ T-cell infiltration was not sufficient to prevent the deterioration of renal function in these mice.

Conclusions: Herein, we successfully developed a protocol wherein MDSCs were differentiated in vitro through combination GM-CSF/IFN-γ treatment. When these MDSCs were subsequently adoptively transferred into a murine model of renal IRI, they aggravated kidney damage, likely owing to the differentiation of M-MDSCs into deleterious macrophages and DCs.
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http://dx.doi.org/10.1159/000518876DOI Listing
September 2021

One-stop preoperative assessment of renal vessels for living donors with 3.0 T non-contrast-enhanced magnetic resonance angiography: compared with computerized tomography angiography and surgical results.

Br J Radiol 2021 Oct 5:20210589. Epub 2021 Oct 5.

Department of Radiology, Tianjin First Center Hospital, School of Medicine, Nankai University, Tianjin, China.

Objective: The study was to investigate the feasibility and accuracy of assessment for living renal donors before transplantation by using 3.0 T non-contrast-enhanced magnetic resonance angiography (NCE-MRA).

Methods: 30 renal donors were investigated and underwent computed tomography angiography (CTA) and 3.0 T NCE-MRA before nephrectomy. Two radiologists independently assessed arterial and venous anatomy and potential kidney lesions. The image quality score, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diameters and lengths of renal arteries and veins were compared between CTA and NCE-MRA. Imaging findings were compared with the surgical results served as reference standard. Agreement was assessed using κ test. The Wilcoxon test and paired sample test were used for statistically significant differences.

Results: The results of image quality score for renal arteries and veins were highly consistent between the two radiologists in NCE-MRA ( < 0.001). There was no significant difference in the scores of renal arterial and venous branches between NCE-MRA and CTA ( > 0.05). The SNR and CNR of renal vessels were higher than CTA ( < 0.001). There were no statistically significant differences in the length of renal vessels measured by the two methods ( > 0.05), and the diameter was smaller than that of CTA ( < 0.05). The detection of normal renal arteries and early branches by both examination techniques was consistent with intraoperative findings. Both methods showed good consistency between the anatomical variation of renal vein and the intraoperative diagnosis ( < 0.001).

Conclusion: 3.0 T NCE-MRA can be used for evaluation of main renal arteries and veins with high accuracy for anatomy and variation classification, and can be used for pre-operative vascular evaluation of living donor kidney transplantation.

Advances In Knowledge: 3.0 T NCE-MRA can be used for evaluation of main renal arteries and veins with high accuracy for anatomy and variation classification, and can be used for pre-operative vascular evaluation of living donor kidney transplantation.
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http://dx.doi.org/10.1259/bjr.20210589DOI Listing
October 2021

Rationally designed upconversion nanoparticles for NIR light-controlled lysosomal escape and nucleus-based photodynamic therapy.

Mikrochim Acta 2021 09 22;188(10):349. Epub 2021 Sep 22.

Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583, Singapore.

Cell nucleus-based photodynamic therapy is a highly effective method for cancer therapy, but it is still challenging to design nucleus-targeting photosensitizers. Here, we propose the "one treatment, multiple irradiations" strategy to achieve nucleus-based photodynamic therapy using the photosensitizer rose bengal (RB)-loaded and mesoporous silica-coated upconversion nanoparticles with the surface modification of amine group (UCNP/[email protected] NPs). After implementation into cancer cells, the rationally designed UCNP/[email protected] NPs could be specifically accumulated in the acidic lysosomes due to their amino group-decorated surface. Upon a short-term (3 min) irradiation of 980 nm near-infrared light, the reactive oxygen species produced by RB through the Förster resonance energy transfer between the upconversion nanoparticles and RB molecules could effectively destroy lysosomes, followed by the release of the UCNP/[email protected] NPs from the lysosomes. Subsequently, these released UCNP/[email protected] NPs could be transferred into the cell nucleus, where a second 980 nm light irradiation was conducted to achieve the nucleus-based photodynamic therapy. The rationally designed UCNP/[email protected] NPs showed excellent anticancer performance in both two-dimensional and three-dimensional cell models using the "one treatment, multiple irradiations" strategy.
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http://dx.doi.org/10.1007/s00604-021-04915-wDOI Listing
September 2021

Terahertz circular dichroism sensing of living cancer cells based on microstructure sensor.

Anal Chim Acta 2021 Oct 24;1180:338871. Epub 2021 Jul 24.

Institute of Modern Optics, Nankai University, Tianjin Key Laboratory of Micro-scale Optical Information Science and Technology, Tianjin, 300350, China; Tianjin Key Laboratory of Optoelectronic Sensor and Sensing Network Technology, Tianjin, 300350, China.

Terahertz (THz) waves have the advantages of being noninvasive and nonionizing because of their low radiation energy, so they have potential applications in the biomedical field, but thus far, those have been limited by the strong absorption in water and low detection sensitivity. Herein, we propose a reflective THz time-domain circular dichroism (CD) sensing system and a silicon subwavelength grating as the microstructure sensor to generate and detect the THz chiral polarization states, to realize quantitative detection of living cell numbers and qualitative identification of cell kinds in a liquid environment. Three kinds of hepatoma cell proliferation and inhibition with different concentrations of aspirin were measured by this sensing method, and the experimental results show that the sensitivities for CD resonance intensity and frequency shift can reach 3.44 dB mL/10 cells and 5.88 GHz mL/10 cells, respectively, and the minimum detection concentration is in the order of 10 cells/mL for THz detection in a liquid environment for the first time. This new THz sensing system and sensing method are expected to become a broadband, label-free, noncontact, real-time detection technology that can be used for quantitative detection and qualitative identification of cells or other active biochemical materials.
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http://dx.doi.org/10.1016/j.aca.2021.338871DOI Listing
October 2021

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

Acta Oncol 2021 Sep 17:1-8. Epub 2021 Sep 17.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Temporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk estimates of TLN after Intensity-Modulated Proton Therapy for HNC.

Material And Methods: Seventy-five temporal lobes from 45 previously treated patients were included in the analysis. Sixteen temporal lobes had radiation associated Magnetic Resonance image changes (TLIC) suspected to be early signs of TLN. Fixed (RWD) and variable RBE-weighed doses (RWD) were calculated using RBE = 1.1 and two RBE models, respectively. RWD and RWD for temporal lobes were compared using Friedman's test. Based on RWD, six NTCP models were fitted and internally validated through bootstrapping. Estimated probabilities from RWD and RWD were compared using paired Wilcoxon test. Seven dose constraints were evaluated separately for RWD and RWD by calculating the observed proportion of TLIC in temporal lobes meeting the specific dose constraints.

Results: RWD were significantly higher than RWD ( < 0.01). NTCP model performance was good (AUC:0.79-0.84). The median difference in estimated probability between RWD and RWD ranged between 5.3% and 20.0% points ( < 0.01), with V and D at the smallest and largest differences, respectively. The proportion of TLIC was higher for RWD (4.0%-13.1%) versus RWD (1.3%-5.3%). For V ≤ 0.03 cc the proportion of TLIC was less than 5% for both RWD and RWD

Conclusion: NTCP estimates were significantly influenced by RBE variations. D as model predictor resulted in the largest deviations in risk estimates between RWD and RWD. V ≤ 0.03 cc was the most consistent dose constraint for RWD and RWD
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http://dx.doi.org/10.1080/0284186X.2021.1979248DOI Listing
September 2021

Downregulation of LINC00115 inhibits the proliferation and invasion of lung cancer cells and .

Ann Transl Med 2021 Aug;9(15):1256

Department of Medical Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Lung cancer is a common malignant tumor in clinical practice. Its morbidity and mortality rank first among malignant tumors. However, the pathogenesis of lung cancer has not been fully clarified. This study found that LINC00115 is highly expressed in lung cancer tissues, but the role and molecular mechanisms of LINC00115 in the occurrence and progression of lung cancer are still unclear.

Methods: Fluorescence quantitative PCR was used to detect the expression of LINC00115 in lung cancer tissues and para-carcinoma tissues. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect the effects of LINC00115 knockdown on the proliferation, clone formation, invasion, and migration of lung cancer cells. Western blot was used to detect the effects of LINC00115 knockdown on the expression of epithelial-mesenchymal transition (EMT)-related molecules. Finally, a xenograft model in nude mice was used to detect the effect of LINC00115 knockdown on the proliferation of lung cancer cells .

Results: Compared with para-carcinoma tissue, LINC00115 was highly expressed in lung cancer tissue. Cell function experiments showed that knockdown of LINC00115 could significantly inhibit the proliferation, invasion, and migration of lung cancer cells. Western blot results showed that knockdown of LINC00115 could significantly inhibit the expression of the EMT-related proteins N-cadherin, vimentin, and fibronectin, and promoted the expression of E-cadherin. In vivo experiments in nude mice showed that knockdown of LINC00115 could significantly inhibit the proliferation of lung cancer tissues .

Conclusions: LINC00115 is highly expressed in lung cancer tissues, and knockdown of LINC00115 can significantly inhibit the proliferation and invasion of lung cancer, which provides a theoretical basis for the design of targeted molecules for the subsequent treatment of lung cancer.
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http://dx.doi.org/10.21037/atm-21-3724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421988PMC
August 2021

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.

JAMA 2021 09;326(10):916-925

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma.

Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma.

Design, Setting, And Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized.

Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks.

Main Outcomes And Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005).

Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively.

Conclusions And Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.
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http://dx.doi.org/10.1001/jama.2021.12836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441593PMC
September 2021

The role of N-cadherin/c-Jun/NDRG1 axis in the progression of prostate cancer.

Int J Biol Sci 2021 25;17(13):3288-3304. Epub 2021 Jul 25.

Department of Urology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

The dysregulation of androgen receptor () signaling is a critical event in the progression of prostate cancer (PCa) and hormone therapy consisting of androgen deprivation (ADT) or AR inhibition is therefore used to treat advanced cases. It is known that N-cadherin becomes upregulated following ADT and can directly induce PCa transformation to the castration-resistant stage (CRPC). However, the relationship between AR and N-cadherin is unclear and may promote better understanding of CRPC pathogenesis and progression. Here, we demonstrate a new axis of N-cadherin/c-Jun/N-myc downstream regulated gene 1 () that N-cadherin promotes c-Jun expression and suppresses NDRG1 to promote invasion and migration of PCa cells through epithelial to mesenchymal transition (EMT). Targeting N-cadherin in combination with enzalutamide (ENZ) treatment synergistically suppressed PC3 cell proliferation and . Further studies showed that compared to lower Gleason score (GS) (GS < 7) cases, high GS (GS > 7) cases exhibited elevated N-cadherin expression and reduced NDRG1 expression, corroborating our observations. We further demonstrate that c-Jun, AR, and DNA methyltransferase-1 () form a complex in the 12-O-tetradecanoyl phorbol-13-acetate (TPA) response elements (TREs) region of the NDRG1 promoter, which suppresses NDRG1 transcription through DNA hypermethylation. In conclusion, we demonstrate an underlying mechanism for how N-cadherin collaborates with AR and NDRG1 to promote CRPC progression. Controlling N-cadherin/c-Jun/NDRG1 axis may help to overcome resistance to commonly used hormone therapy to improve long-term patient outcomes.
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http://dx.doi.org/10.7150/ijbs.63300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416735PMC
July 2021

Uniform platinum nanoparticles loaded on Universitetet i Oslo-66 (UiO-66): Active and stable catalysts for gas toluene combustion.

J Colloid Interface Sci 2021 Aug 21;606(Pt 2):1811-1822. Epub 2021 Aug 21.

School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address:

Highly dispersed Pt nanoparticles supported UiO-66 catalysts were successfully prepared by the incipient wetness impregnation method. Their thermal catalytic performances were evaluated by toluene degradation. The physicochemical properties of the samples were characterized using a series of characterization methods. The catalytic activity of catalysts remained essentially unchanged in the high weight hourly space velocity, stability and water resistance test, which also indicated good catalytic performance. In the reusability test, the catalytic performance was found to be enhanced after the reaction, because of the catalyst might follow a Pt-PtO synergistic catalytic mechanism (similar to Mars-van Krevelen mechanism) and there was a phase transition between Pt and PtO during the reaction. Firstly, the toluene adsorbed on the catalyst surface was oxidized by the activated lattice oxygen of the PtO. Then, consumption of oxygen atoms led to formation of oxygen vacancies, and finally the molecular oxygen adsorbed by Pt was activated and passed to the PtO to supplement the oxygen vacancies, forming a redox cycle. In addition, the possible catalytic oxidation mechanism of toluene was also revealed.
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http://dx.doi.org/10.1016/j.jcis.2021.08.127DOI Listing
August 2021

Enhanced removal of Cr(VI) from aqueous solution by stabilized nanoscale zero valent iron and copper bimetal intercalated montmorillonite.

J Colloid Interface Sci 2021 Aug 18;606(Pt 2):941-952. Epub 2021 Aug 18.

School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai, 200093, China. Electronic address:

Batch experiments were conducted to study the Cr(VI) removal by nanoscale zero valent iron and copper intercalated montmorillonite (MMT-nFe/Cu) nanocomposite. MMT-nFe/Cu was characterized using SEM, TEM, XRD, FTIR, N adsorption-desorption isotherms and XPS. The results demonstrated that highly dispersed nanoscale Fe/Cu (nFe/Cu) were successfully introduced into the montmorillonite (MMT) layers. In the reaction process, the combination of Cu and Fe acted as a galvanic cell, and electrocorrosion not only speeded up the reaction rate, but also increased reduction activity of nFe. MMT-nFe/Cu as an excellent carrier had good functions in dispersing nFe and Cu particles, pH buffering and could keep nFe and Cu particles from being released. Besides, no iron ions and very low concentrations of copper ions released in the reaction system, which greatly avoided the influence of secondary environmental pollution.
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http://dx.doi.org/10.1016/j.jcis.2021.08.075DOI Listing
August 2021

Field study of microbial community structure and dechlorination activity in a multi-solvents co-contaminated site undergoing natural attenuation.

J Hazard Mater 2021 Aug 23;423(Pt A):127010. Epub 2021 Aug 23.

Department of Environmental Science and Engineering, School of Energy and Environment, Southeast University, Nanjing, Jiangsu, China. Electronic address:

BTEX and chlorinated aliphatic hydrocarbons (CAHs) are the common pollutants found at contaminated sites, and natural attenuation (NA) of CAHs was widely observed where they coexist. In this work, the groundwater in a site co-contaminated with BTEX and CAHs was monitored for 1 year. The compositions and activities of the microfloras, especially dechlorinators and their relationships with the contaminants, geochemical properties, seasons and depth were evaluated. The results are consistent with the well-known NA conceptual model where CAHs are not able to stimulate the enrichment of dechlorinators alone, but BTEX does promote dechlorination. The higher temperature, rather than ORP in the deeper groundwater of the wet season became a key factor to promote the abundance of dechlorinators, but only when BTEX was available, indicating that the substrates from the BTEX biodegradation played an important role in the dechlorinator enrichment. The elevated ORP in the shallower groundwater exceeded the optimum conditions for reductive dechlorination and no significant seasonal variation of dechlorinators was found. The co-occurrence network revealed the cooperative interactions among the functional microfloras in which dechlorinators, BTEX degraders, and fermentative bacteria jointly promoted the dechlorination. These findings provided us a further understanding of the NA processes in a commingled plume.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127010DOI Listing
August 2021

Divergent responses of CO and CH fluxes to changes in the precipitation regime on the Tibetan Plateau: Evidence from soil enzyme activities and microbial communities.

Sci Total Environ 2021 Aug 12;801:149604. Epub 2021 Aug 12.

Institute of Wetland Research, Chinese Academy of Forestry, Beijing 100091, China; Beijing Key Laboratory of Wetland Services and Restoration, Beijing 100091, China; Sichuan Zoige Wetland Ecosystem Research Station, Tibetan Autonomous Prefecture of Aba, 624500, Sichuan, China. Electronic address:

Carbon fluxes (CO and CH) are important indicators of the response of alpine meadow ecosystems to global climate change. Alpine meadows on the Qinghai-Tibet Plateau are sensitive to climate change. Although the temporal allocation of precipitation can vary, its intensity is expected to increase, and its frequency is expected to decrease in the future. In this study, a manipulative field experiment was conducted to investigate how carbon fluxes are altered in response to moderate and severe changes in the precipitation regime. Fluctuations in CH flux were large under a severely altered precipitation regime (range of -0.048-0.038 mg m h). Severe changes in the precipitation regime significantly reduced soil CH uptake by approximately 54.3%. This was probably affected by the decrease in the dissolved organic carbon concentration and changes in the microbial community (mainly Gammaproteobacteria), which were induced by variation in soil water conditions under various precipitation regimes. Under moderate changes in the precipitation regime, the average value of CO fluxes (ecosystem respiration) was 698.21 ± 35.19 mg m h, which was significantly decreased by 20.7% compared with the control. This likely stems from the suppression of enzyme activity (particularly α-1,4-glucosidase and β-1,4-glucosidase) and the alteration of microbial community structure in this treatment, which led to a decrease in organic matter breakdown and a reduction in the release of CO to the atmosphere. However, CO fluxes were slightly (i.e., not significantly) decreased under the severely altered precipitation regime. Such different responses of CO flux are probably driven by differences in microbial strategies. This study not only increases our understanding of the mechanisms underlying the adaptation of alpine meadow ecosystems to global climate change but also provides new insight into the carbon source/sink functions of alpine meadows.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149604DOI Listing
August 2021

Opportunistic pathogens exhibit distinct growth dynamics in rainwater and tap water storage systems.

Water Res 2021 Oct 19;204:117581. Epub 2021 Aug 19.

State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

Opportunistic pathogens (OPs) are emerging microbial contaminants in engineered water systems, yet their growth potential in rainwater systems has not been evaluated. The purpose of this study was to compare the growth dynamics of bacterial OPs and related genera (Pseudomonas aeruginosa, Legionella spp., L. pneumophila, Mycobacterium spp., and M. avium), two amoebal hosts (Acanthamoeba spp. and Vermamoeba vermiformis), and the fecal indicator Escherichia coli in simulated rainwater and tap water storage systems (SWSSs). Quantitative polymerase chain reaction (q-PCR) analysis of target microorganisms in SWSS influents and effluents demonstrated that P. aeruginosa and Legionella thrived in rainwater, but not in tap water. V. vermiformis proliferated in both rainwater and tap water polyvinyl chloride (PVC) SWSSs, while mycobacteria were largely absent in rainwater SWSSs. Tank materials exerted stronger influence on target microorganisms in rainwater SWSSs relative to tap water SWSSs, with species-specific responses noted in bulk water and biofilm. For instance, P. aeruginosa and V. vermiformis had the highest gene copy numbers in PVC rainwater SWSS effluents and biofilm, while Legionella peaked in stainless steel rainwater SWSS effluents and PVC rainwater SWSS biofilm. These results highlighted the OP contamination risks in rainwater storage systems and provided insights into rainwater system design and operation in terms of OP control.
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http://dx.doi.org/10.1016/j.watres.2021.117581DOI Listing
October 2021

The role of Nrf2 pathway in alleviating fluorine-induced apoptosis by different selenium sources in the chicken duodenum and jejunum.

Ecotoxicol Environ Saf 2021 Aug 27;224:112708. Epub 2021 Aug 27.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology • College of Veterinary Medicine, Zhejiang A & F University, Linan 311300, China. Electronic address:

In order to evaluate the alleviative effects and molecular mechanisms of sodium selenite (SS) and selenomethionine (SM) on excessive apoptosis induced by high fluorine (HF) in the duodenum and jejunum of broilers, 720 1 day old Lingnan Yellow broilers were randomly divided into 4 groups (each group assigned 180 chickens with 6 replicates) and offered either a control diet or test diets (800 mg/kg F, HF group; 800 mg/kg F + 0.15 mg selenium (Se)/kg as SS (SS group) or SM (SM group)) for 50 days. High F intake significantly increased (P < 0.05) apoptosis rates of duodenum and jejunum by inducing oxidative stress and leading to mitochondrial damage. Selenomethionine supplementation effectively alleviated mitochondrial damage and severe apoptosis of duodenum and jejunum caused by HF through decreasing oxidative stress parameters. Selenomethionine added group significantly increased (P < 0.05) nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and nuclear Nrf2 protein levels as well as Nrf2 downstream antioxidant enzymes expressions in the duodenum and jejunum when compared with the HF group. Selenomethionine was superior to SS in activating the Nrf2 pathway and reducing the apoptosis rate of duodenum. It was concluded that dietary SM supplementation could ameliorate F-induced excessive apoptosis by inducing the Nrf2 pathway. Our findings will bring a promising tactics for the utilization of SM as an efficient antioxidant additive for reducing the intestinal damage caused by fluorosis in poultry.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112708DOI Listing
August 2021

PMA induces the differentiation of monocytes into immunosuppressive MDSCs.

Clin Exp Immunol 2021 Nov 9;206(2):216-225. Epub 2021 Sep 9.

Institute of Uro-Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

The induction of immune tolerance without the use of immunosuppressive drugs is a crucial problem in organ transplantation. The use of myeloid-derived suppressor cells (MDSCs) as a cell-based adjuvant immunosuppressive therapy is a bright clinical prospect in organ transplantation. MDSCs with stable immunosuppressive activities can be used to treat immune-related diseases. In this study, macrophage colony-stimulating factor (M-CSF) was used to promote myeloid progenitor cell differentiation, and phorbol 12-myristate 13-acetate (PMA) was added to induce MDSCs at the later stage of induction in vitro. Cell phenotypes were detected by flow cytometry and mRNA was detected by real-time-polymerase chain reaction (RT-PCR). A mouse skin transplantation model was used to investigate the cell inhibitory function. The combination of PMA and M-CSF induced the differentiation of myeloid-derived monocytes into MDSCs. MDSCs were found to induce immune tolerance by inhibiting the proliferation and activation of T cells, promoting cytokine secretion and inducing T cell transformation to regulatory T cells (T ). PMA significantly up-regulated the expression of Arg-1 and the Arg-1 protein expression in MDSCs and arginase 1 (Arg-1) inhibitor nor-NOHA reversed the MDSC immunosuppressive activity, indicating the involvement of the Arg-1 pathway in MDSC-mediated immunosuppression. M-CSF + PMA-induced MDSCs also significantly prolonged the survival time of skin grafts in mice, showing that MDSCs exert immunosuppressive effects in vivo. We describe a novel scheme to induce immunosuppressive MDSCs in vitro. MDSCs induced by M-CSF with PMA showed stable immunosuppression. MDSCs induced by this protocol may benefit patients with organ transplantation through immune regulation.
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http://dx.doi.org/10.1111/cei.13657DOI Listing
November 2021

A Self-Established "Machining-Measurement-Evaluation" Integrated Platform for Taper Cutting Experiments and Applications.

Micromachines (Basel) 2021 Aug 4;12(8). Epub 2021 Aug 4.

State Key Laboratory of Precision Measuring Technology and Instruments, Laborotary of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072, China.

Taper-cutting experiments are important means of exploring the nano-cutting mechanisms of hard and brittle materials. Under current cutting conditions, the brittle-ductile transition depth (BDTD) of a material can be obtained through a taper-cutting experiment. However, taper-cutting experiments mostly rely on ultra-precision machining tools, which have a low efficiency and high cost, and it is thus difficult to realize in situ measurements. For taper-cut surfaces, three-dimensional microscopy and two-dimensional image calculation methods are generally used to obtain the BDTDs of materials, which have a great degree of subjectivity, leading to low accuracy. In this paper, an integrated system-processing platform is designed and established in order to realize the processing, measurement, and evaluation of taper-cutting experiments on hard and brittle materials. A spectral confocal sensor is introduced to assist in the assembly and adjustment of the workpiece. This system can directly perform taper-cutting experiments rather than using ultra-precision machining tools, and a small white light interference sensor is integrated for in situ measurement of the three-dimensional topography of the cutting surface. A method for the calculation of BDTD is proposed in order to accurately obtain the BDTDs of materials based on three-dimensional data that are supplemented by two-dimensional images. The results show that the cutting effects of the integrated platform on taper cutting have a strong agreement with the effects of ultra-precision machining tools, thus proving the stability and reliability of the integrated platform. The two-dimensional image measurement results show that the proposed measurement method is accurate and feasible. Finally, microstructure arrays were fabricated on the integrated platform as a typical case of a high-precision application.
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http://dx.doi.org/10.3390/mi12080929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399202PMC
August 2021

Cumulative live birth rates between GnRH-agonist long and GnRH-antagonist protocol in one ART cycle when all embryos transferred: real-word data of 18,853 women from China.

Reprod Biol Endocrinol 2021 Aug 12;19(1):124. Epub 2021 Aug 12.

Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China.

Background: A consensus has been reached on the preferred primary outcome of all infertility treatment trials, which is the cumulative live birth rate (CLBR). Some recent randomized controlled trials (RCTs) and retrospective studies have compared the effectiveness of GnRH-antagonist and GnRH-agonist protocols but showed inconsistent results. Studies commonly used conservative estimates and optimal estimates to described the CLBR of one incomplete assisted reproductive technology (ART) cycle and there are not many previous studies with data of the complete cycle to compare CLBRs in GnRH-antagonist versus GnRH-agonist protocols.

Methods: A total of 18,853 patients have completed their first IVF cycle including fresh and subsequent frozen-thawed cycles during 2016-2019, 16,827 patients were treated with GnRH-a long and 2026 patients with GnRH-ant protocol. Multivariable logistic analysis was used to evaluate the difference of GnRH-a and GnRH-ant protocol in relation to CLBR. Utilized Propensity Score Matching(PSM) for sampling by up to 1:1 nearest neighbor matching to adjust the numerical difference and balance the confounders between groups.

Results: Before PSM, significant differences were observed in baseline characteristics and the CLBR was 50.91% in the GnRH-a and 33.42% in the GnRH-ant (OR = 2.07; 95%CI: 1.88-2.28; P < 0.001). Stratified analysis showed the CLBR of GnRH-ant was lower than GnRH-a in suboptimal responders(46.89 vs 27.42%, OR = 2.34, 95%CI = 1.99-2.74; P < 0.001) and no differences of CLBR were observed in other patients between protocols. After adjusting for potential confounders, multivariable logistic analysis found the CLBR of GnRH-ant group was lower than that of GnRH-a group (OR = 2.11, 95%CI:1.69-2.63, P < 0.001). After PSM balenced the confounders between groups, the CLBR of GnRH-a group was higher than that of GnRH-ant group in suboptimal responders((38.61 vs 28.22%, OR = 1.60, 95%CI = 1.28-1.99; P < 0.001) and the normal fertilization rate and number of available embryo in GnRH-a were higher than these of GnRH-ant groups in suboptimal responders (77.39 vs 75.22%; 2.86 ± 1.26 vs 2.61 ± 1.22; P < 0.05). No significant difference was observed in other patients between different protocols.

Conclusions: It is crucial to optimize the utilization of protocols in different ovarian response patients and reconsider the field of application of GnRH-ant protocols in China.
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http://dx.doi.org/10.1186/s12958-021-00814-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359059PMC
August 2021

HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver.

Theranostics 2021 25;11(17):8362-8378. Epub 2021 Jul 25.

Department of Gastrointestinal Cancer Biology, Tianjin Cancer Institute, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, P.R. China.

Hepatitis B x protein (HBx) is required to initiate and maintain the replication of hepatitis B virus (HBV). Protein arginine methyltransferases 5 (PRMT5) negatively regulates HBV transcription. WD repeat domain 77 protein (WDR77) greatly enhances the methyltransferase activity of PRMT5. However, the role of WDR77 in the modulation of cccDNA transcription and HBV replication is poorly understood. In this study, we investigated the mechanism by which HBx modulated HBV replication involving WDR77 in the liver. A human liver-chimeric mouse model was established. Immunohistochemistry (IHC) staining, Western blot analysis, Southern blot analysis, Northern blot analysis, immunofluorescence assays, ELISA, RT-qPCR, CoIP assays, and ChIP assays were performed in human liver-chimeric mouse model, primary human hepatocytes (PHHs), HepG2-NTCP, dHepaRG and HepG2 cell lines. HBV infection and HBx expression remarkably reduced the protein levels of WDR77 in human liver-chimeric mice and HepG2-NTCP cells. WDR77 restricted cccDNA transcription and HBV replication in PHHs and HepG2-NTCP cells. Mechanically, WDR77 enhanced PRMT5-triggered symmetric dimethylation of arginine 3 on H4 (H4R3me2s) on the cccDNA minichromosome to control cccDNA transcription. HBx drove the cellular DDB1-containing E3 ubiquitin ligase to degrade WDR77 through recruiting WDR77, leading to the disability of methyltransferase activity of PRMT5. Thus, HBx promoted HBV replication by driving a positive feedback loop of HBx-DDB1/WDR77/PRMT5/H4R3me2s/cccDNA/HBV/HBx in the liver. HBx attenuates the WDR77-mediated HBV repression by driving DDB1-induced WDR77 degradation in the liver. Our finding provides new insights into the mechanism by which HBx enhances HBV replication in the liver.
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http://dx.doi.org/10.7150/thno.57531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343998PMC
July 2021

Open-Ended Metallodithiolene Complexes with the 1,2,4,5-Tetrakis(diphenylphosphino)benzene Ligand: Modular Building Elements for the Synthesis of Multimetal Complexes.

Inorg Chem 2021 Sep 9;60(17):13177-13192. Epub 2021 Aug 9.

Department of Chemistry, Tulane University, 6400 Freret Street, New Orleans, Louisiana 70118, United States.

Open-ended, singly metalated dithiolene complexes with 1,2,4,5-tetrakis(diphenylphosphino)benzene (tpbz) are prepared either by ligand transfer to [ClM(tpbz)] from (RCS)SnR' (R = CN, R' = Me; R = Me, R' = Bu) or by a direct reaction between tpbz and [M(SCR)] (M = Ni, Pd, Pt; R = Ph, -anisyl) in a 1:1 ratio. The formation of dimetallic [(RCS)M(tpbz)M(SCR)] attends these syntheses in modest amounts, but the open-ended compounds are readily separated by silica chromatography. As affirmed by X-ray crystallographic characterization of numerous members of the set, the [(RCS)M(tpbz)] compounds show dithiolene ligands in their fully reduced ene-1,2-dithiolate form conjoined with divalent Group 10 ions. Minor amounts of octahedral [(PhCS)Pt(tpbz)], a presumed intermediate, are isolated from the preparation of [(PhCS)Pt(tpbz)]. Heterodimetallic [(PhCS)Pt(tpbz)Ni(SCMe)] is prepared from [(PhCS)Pt(tpbz)]; its cyclic voltammogram, upon anodic scanning, shows two pairs of closely spaced, but resolved, 1e oxidations corresponding first to [RCS] - 1e → [RCSS] and then to [RCSS] - 1e → [R(C═S)]. The open diphosphine of [(RCS)M(tpbz)] can be oxidized to afford open-ended [(RCS)M(tpbzE)] (E = O, S). Synthesis of the octahedral [(dppbO)Ni][I] [dppbO = 1,2-bis(diphenylphosphoryl)benzene] suggests that the steric profile of [(RCS)M(tpbzE)] is moderated enough that three could be accommodated as ligands around a metal ion.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424627PMC
September 2021

Microblog Topic-Words Detection Model for Earthquake Emergency Responses Based on Information Classification Hierarchy.

Int J Environ Res Public Health 2021 07 28;18(15). Epub 2021 Jul 28.

School of Information Science and Technology, Beijing Forestry University, Beijing 100083, China.

Social media data are constantly updated, numerous, and characteristically prominent. To quickly extract the needed information from the data to address earthquake emergencies, a topic-words detection model of earthquake emergency microblog messages is studied. First, a case analysis method is used to analyze microblog information after earthquake events. An earthquake emergency information classification hierarchy is constructed based on public demand. Then, subject sets of different granularities of earthquake emergency information classification are generated through the classification hierarchy. A detection model of new topic-words is studied to improve and perfect the sets of topic-words. Furthermore, the validity, timeliness, and completeness of the topic-words detection model are verified using 2201 messages obtained after the 2014 Ludian earthquake. The results show that the information acquisition time of the model is short. The validity of the whole set is 96.96%, and the average and maximum validity of single words are 78% and 100%, respectively. In the Ludian and Jiuzhaigou earthquake cases, new topic-words added to different earthquakes only reach single digits in validity. Therefore, the experiments show that the proposed model can quickly obtain effective and pertinent information after an earthquake, and the complete performance of the earthquake emergency information classification hierarchy can meet the needs of other earthquake emergencies.
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http://dx.doi.org/10.3390/ijerph18158000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345666PMC
July 2021

Compressed-sensing accelerated magnetic resonance imaging of inner ear.

J Appl Clin Med Phys 2021 Sep 4;22(9):332-338. Epub 2021 Aug 4.

Department of Radiology, Peking University First Hospital, Beijing, 100034, China.

Objective: To compare conventional method and compressed-sensing (CS) accelerated 3D balanced fast field echo imaging (bFFE) of inner ear.

Methods: Twenty patients with suspected inner ear disease underwent CS accelerated 3D-bFFE (CS-bFFE) and conventional 3D-bFFE (Con-bFFE) by a 3T MRI. The overall image quality, motion artifacts, and image quality of specific structures of inner ear were assessed on ordinal scales by three radiologists who were blinded to the scan protocols. Kendall W test was used to evaluate interobserver agreement and Wilcoxon test was performed to compare the image quality and motion artifacts between CS-bFFE and Con-bFFE.

Results: The acquisition duration of CS-bFFE (1 min 53 s) was 49% faster than Con-bFFE. Three radiologists had good inter-observer agreement of image quality (Kendall W value of 0.829 for CS-bFFE and 0.815 for Con-bFFE) and motion artifacts evaluation (Kendall W value of 0861 for CS-bFFE and 0.707 for Con-bFFE). The better overall image quality of CS-bFFE was assessed (4.93 ± 0.23 for CS-bFFE, 4.53 ± 0.70 for Con-bFFE, Z = -2.254, p = 0.024). The image quality score of facial and cochlear nerve gained higher in CS-bFFE (4.93 ± 0.23 for CS-bFFE, 4.58 ± 0.64 for Con-bFFE, Z = -2.094, p = 0.036). No significant difference of motion artifacts (p = 0.050) between CS-bFFE and Con-bFFE.

Conclusions: The CS-bFFE improves image quality and reduces acquisition time significantly, and it is a feasible MRI protocol for inner ear imaging.
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http://dx.doi.org/10.1002/acm2.13383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425888PMC
September 2021

Restoration of dystrophin expression in mice by suppressing a nonsense mutation through the incorporation of unnatural amino acids.

Nat Biomed Eng 2021 Aug 2. Epub 2021 Aug 2.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Approximately 11% of monogenic diseases involve nonsense mutations that are caused by premature termination codons. These codons can in principle be read-through via the site-specific incorporation of unnatural amino acids to generate full-length proteins with minimal loss of function. Here we report that aminoacyl-tRNA-synthase-tRNA pairs specific for the desired unnatural amino acids can be used to read through a nonsense mutation in the dystrophin gene. We show partial restoration of dystrophin expression in differentiated primary myoblasts (from a mdx mouse model and a patient with Duchenne muscular dystrophy), and restoration of muscle function in two mouse models: mdx mice, via viral delivery of the engineered tRNA-synthase-tRNA pair intraperitoneally or intramuscularly and of the associated unnatural amino acid intraperitoneally; and mice produced by crossing mdx mice and transgenic mice with a chromosomally integrated pair, via intraperitoneal delivery of the unnatural amino acid. The incorporation of unnatural amino acids to restore endogenous protein expression could be explored for therapeutic use.
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http://dx.doi.org/10.1038/s41551-021-00774-1DOI Listing
August 2021

M-CSF and prostratin induced Mregs promote immune tolerance in transplanted mice through Arg-1 pathway.

Int Immunopharmacol 2021 Oct 29;99:108014. Epub 2021 Jul 29.

Department of Urology, Capital Medical University Beijing Chaoyang Hospital, Beijing, China. Electronic address:

Objective: Regulatory macrophages (Mregs) are a group of heterogeneous macrophages. These cells could induce immunosuppressive effects through the expression of immune regulatory molecules and cytokines.

Methods: The differentiation of Mregs was induced by treating bone marrow cells with M-CSF and prostratin in vitro. The cell-phenotypes and immunosuppressive function were determined by flow cytometry. Rt-PCR was employed to assess the mechanisms of Mregs. Skin grafted mouse model was used for in vivo validation.

Results: Mregs induced by M-CSF + prostratin had a strong inhibitory effect on T cell proliferation and cytokines production. The phenotype of induced bone marrow cells changed towards Mregs. These Mregs could induce the differentiation of Tregs in vivo. Arg-1 expression in these cells were significantly upregulated. Inhibition of arginase (Arg) or arginine supplement significantly reversed the immunosuppressive function. In mice skin-grafted models, adoptive transfer of these Mregs significantly prolonged allograft survival. In mice models, Arg-1 expression significantly elevated on skin grafts cells and Tregs increased in graft tissues.

Conclusions: We successfully developed a Mregs-inducing protocol with the combination of M-CSF and prostratin in vitro. M-CSF + prostratin induced Mregs prevented mice skin graft rejection through upregulating the expression Arg-1.
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http://dx.doi.org/10.1016/j.intimp.2021.108014DOI Listing
October 2021
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