Publications by authors named "Yifan Wang"

590 Publications

Cetuximab-Modified Human Serum Albumin Nanoparticles Co-Loaded with Doxorubicin and MDR1 siRNA for the Treatment of Drug-Resistant Breast Tumors.

Int J Nanomedicine 2021 16;16:7051-7069. Epub 2021 Oct 16.

School of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, People's Republic of China.

Background: Breast cancer is the most prevalent cancer among women. Doxorubicin (DOX) is a common chemotherapeutic drug used to treat many different cancers. However, multidrug resistance limits the treatment of breast cancer. MDR1 siRNA (siMDR1) combinatorial therapy has attracted significant attention as a breakthrough therapy for multidrug resistance in tumors. However, naked siRNA is easily degraded by enzymatic hydrolysis requiring an siRNA carrier for its protection. Human serum albumin (HSA) was selected as the carrier due to its excellent biocompatibility, non-toxicity, and non-immunogenicity. Cetuximab was used to modify the HSA nanoparticles in order to target the tumor tissues.

Methods: This study used a central composite design response surface methodology (CCD-RSM) to investigate the optimal formula for HSA NPs preparation. Cex-HSA/DOX/MDR1 siRNA (C-H/D/M) was characterized by dynamic light scattering and transmission electron microscopy. The efficacy of C-H/D/M tumor growth inhibitory activity was investigated in vitro and in vivo using confocal imaging, MTT assay, and an MCF-7/ADR tumor-bearing mice model. RT-qPCR, ELISA analysis, and flow cytometry were used to investigate the in vitro antitumor mechanisms of C-H/D/M.

Results: The diameter and PDI of the C-H/D/M were 173.57 ± 1.30 nm and 0.027 ± 0.004, respectively. C-H/D/M promoted and maintained the sustained release and the uptake of DOX significantly. After transfection, the MDR1 mRNA and P-gp expression levels were down-regulated by 44.31 ± 3.6% (P < 0.01) and 38.08 ± 2.4% (P < 0.01) in an MCF-7/ADR cell line. The fluorescent images of the treated BALB/c nude mice revealed that C-H/D/M achieved targeted delivery of siMDR1 and DOX into the tumor tissue. The in vivo tumor inhibition results demonstrated that the tumor inhibition rate of the C-H/D/M treated group was 54.05% ± 1.25%. The biosafety results indicated that C-H/D/M did not induce significant damages to the main organs in vivo.

Conclusion: C-H/D/M can be used as an ideal non-viral tumor-targeting vector to overcome MDR and enhance the antitumor effect.
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http://dx.doi.org/10.2147/IJN.S332830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528549PMC
October 2021

The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.

Nat Commun 2021 Oct 26;12(1):6173. Epub 2021 Oct 26.

Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.

The proteasome, the primary protease for ubiquitin-dependent proteolysis in eukaryotes, is usually found as a mixture of 30S, 26S, and 20S complexes. These complexes have common catalytic sites, which makes it challenging to determine their distinctive roles in intracellular proteolysis. Here, we chemically synthesize a panel of homogenous ubiquitinated proteins, and use them to compare 20S and 26S proteasomes with respect to substrate selection and peptide-product generation. We show that 20S proteasomes can degrade the ubiquitin tag along with the conjugated substrate. Ubiquitin remnants on branched peptide products identified by LC-MS/MS, and flexibility in the 20S gate observed by cryo-EM, reflect the ability of the 20S proteasome to proteolyze an isopeptide-linked ubiquitin-conjugate. Peptidomics identifies proteasome-trapped ubiquitin-derived peptides and peptides of potential 20S substrates in Hi20S cells, hypoxic cells, and human failing-heart. Moreover, elevated levels of 20S proteasomes appear to contribute to cell survival under stress associated with damaged proteins.
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http://dx.doi.org/10.1038/s41467-021-26427-0DOI Listing
October 2021

Obstacle Avoidance Path Planning for Worm-like Robot Using Bézier Curve.

Biomimetics (Basel) 2021 Sep 30;6(4). Epub 2021 Sep 30.

Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.

Worm-like robots have demonstrated great potential in navigating through environments requiring body shape deformation. Some examples include navigating within a network of pipes, crawling through rubble for search and rescue operations, and medical applications such as endoscopy and colonoscopy. In this work, we developed path planning optimization techniques and obstacle avoidance algorithms for the peristaltic method of locomotion of worm-like robots. Based on our previous path generation study using a modified rapidly exploring random tree (RRT), we have further introduced the Bézier curve to allow more path optimization flexibility. Using Bézier curves, the path planner can explore more areas and gain more flexibility to make the path smoother. We have calculated the obstacle avoidance limitations during turning tests for a six-segment robot with the developed path planning algorithm. Based on the results of our robot simulation, we determined a safe turning clearance distance with a six-body diameter between the robot and the obstacles. When the clearance is less than this value, additional methods such as backward locomotion may need to be applied for paths with high obstacle offset. Furthermore, for a worm-like robot, the paths of subsequent segments will be slightly different than the path of the head segment. Here, we show that as the number of segments increases, the differences between the head path and tail path increase, necessitating greater lateral clearance margins.
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http://dx.doi.org/10.3390/biomimetics6040057DOI Listing
September 2021

NEXTorch: A Design and Bayesian Optimization Toolkit for Chemical Sciences and Engineering.

J Chem Inf Model 2021 Oct 25. Epub 2021 Oct 25.

Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy St., Newark, Delaware 19716, United States.

Automation and optimization of chemical systems require well-informed decisions on what experiments to run to reduce time, materials, and/or computations. Data-driven active learning algorithms have emerged as valuable tools to solve such tasks. Bayesian optimization, a sequential global optimization approach, is a popular active-learning framework. Past studies have demonstrated its efficiency in solving chemistry and engineering problems. We introduce NEXTorch, a library in Python/PyTorch, to facilitate laboratory or computational design using Bayesian optimization. NEXTorch offers fast predictive modeling, flexible optimization loops, visualization capabilities, easy interfacing with legacy software, and multiple types of parameters and data type conversions. It provides GPU acceleration, parallelization, and state-of-the-art Bayesian optimization algorithms and supports both automated and human-in-the-loop optimization. The comprehensive online documentation introduces Bayesian optimization theory and several examples from catalyst synthesis, reaction condition optimization, parameter estimation, and reactor geometry optimization. NEXTorch is open-source and available on GitHub.
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http://dx.doi.org/10.1021/acs.jcim.1c00637DOI Listing
October 2021

Engineering the endoplasmic reticulum secretory pathway in Trichoderma reesei for improved cellulase production.

Enzyme Microb Technol 2021 Oct 4;152:109923. Epub 2021 Oct 4.

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

The filamentous fungus Trichoderma reesei is an extraordinarily efficient cell factory of industrial cellulase for production of biofuels and other bio-based products because of its excellent potential to secrete cellulolytic enzymes. Engineering the protein secretory pathway may be a powerful means for efficient protein production. However, it is uncertain whether this engineering approach could improve cellulase production in T. reesei. Herein, the endoplasmic reticulum (ER) secretory pathway was engineered for the production of cellulolytic enzymes by multiple strategies, including: (I) overexpression of the key components of protein folding (Pdi1, Ero1 and BiP); (II) overexpression of the glycosylation-related elements (Gpt1 and Gls2); (III) knockout of the ER mannosidase I (Mns1) encoding gene mns1. By utilizing these ER engineering strategies, the secretion of β-glucosidase was remarkably elevated in the engineered strains, ranging from 29.2 % to 112.5 %. Furthermore, it was found that engineering these components also regulated the ER stress resistance. More importantly, the total cellulase production was increased with varying degrees, which reached a maximum of 149.4 %, using the filter paper assay (FPA) as a characterization method. These results demonstrated that engineering the ER secretory pathway can enhance protein secretion, particularly for cellulase production, which shed light for the development of high-efficient cellulolytic enzymes for economically feasible bioethanol production from lignocellulosic biomass.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109923DOI Listing
October 2021

A Declining Trend in China's Future Cropland-NO Emissions Due to Reduced Cropland Area.

Environ Sci Technol 2021 Oct 22. Epub 2021 Oct 22.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875, China.

Croplands are the largest anthropogenic source of nitrous oxide (NO), a powerful greenhouse gas that contributes to the growing atmospheric NO burden. However, few studies provide a comprehensive depiction of future cropland-NO emissions on a national scale due to a lack of accurate cropland prediction data. Herein, we present a newly developed distributed land-use change prediction model for the high-precision prediction of national-scale land-use change. The high-precision land-use data provide an opportunity to elucidate how the changes in cropland area will affect the magnitude and spatial distribution of NO emissions from China's croplands during 2020-2070. The results showed a declining trend in China's total cropland-NO emissions from 0.44 ± 0.03 Tg N/year in 2020 to 0.39 ± 0.07 Tg N/year in 2070, consistent with a cropland area reduction from (1.78 ± 0.02) × 10 ha to (1.40 ± 0.15) × 10 ha. However, approximately 31% of all calculated cities in China would emit more than the present level. Furthermore, different land use and climate change scenarios would have important impacts on cropland-NO emissions. The Grain for Green Plan implemented in China would effectively control emissions by approximately 12%.
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http://dx.doi.org/10.1021/acs.est.1c03612DOI Listing
October 2021

A comparison of two different surgical procedures in the treatment of isolated spinal metastasis patients with metastatic spinal cord compression: a case-control study.

Eur Spine J 2021 Oct 19. Epub 2021 Oct 19.

Department of Orthopedics, Orthopaedic Oncology Center, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai, Huangpu District, China.

Objective: The aim of the study was to compare total en bloc spondylectomy (TES) and separation surgery with postoperative stereotactic radiosurgery (SSRS) for isolated metastatic patients with spinal cord compression by assessing recurrence-free survival (RFS), overall survival (OS), postoperative complications, and quality of life scores (QoL).

Methods: From October 2013 to December 2020, 52 isolated spinal metastasis patients with cord compression were selected and separated into two groups based on the surgical method used (TES group, n = 26; and SSRS group, n = 26). Indexes for evaluation included postoperative Frankel grade, postoperative ECOG-PS, RFS, OS, postoperative complications, operation time, intraoperative blood loss, and QoL.

Results: The average follow-up duration was 31.44 months. There was no significant difference (P > 0.05) in postoperative complications and OS between the two groups. However, a significant difference in operation time, intraoperative blood loss, postoperative ECOG-PS, RFS, and mental health domain (6 months after surgery) was found between the two groups (P < 0.05). According to The Spine Oncology Study Group Outcomes Questionnaire assessment, the total pain and physical function domains scores were also elevated after surgery in both groups. However, no significant difference was observed between groups A and B (p = 0.450 and 0.446, respectively).

Conclusions: TES and SSRS were efficient methods for treating solitary spinal metastasis patients with metastatic spinal cord compression. Better local tumor control and mental health were found in the TES group, and most patients felt as if they were free of spinal tumors. Compared with TES, the SSRS caused less operation-related trauma. However, there was no significant difference in OS between the two groups.
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http://dx.doi.org/10.1007/s00586-021-07032-7DOI Listing
October 2021

A new regime of heme-dependent aromatic oxygenase superfamily.

Proc Natl Acad Sci U S A 2021 Oct;118(43)

Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249

Two histidine-ligated heme-dependent monooxygenase proteins, TyrH and SfmD, have recently been found to resemble enzymes from the dioxygenase superfamily currently named after tryptophan 2,3-dioxygenase (TDO), that is, the TDO superfamily. These latest findings prompted us to revisit the structure and function of the superfamily. The enzymes in this superfamily share a similar core architecture and a histidine-ligated heme. Their primary functions are to promote O-atom transfer to an aromatic metabolite. TDO and indoleamine 2,3-dioxygenase (IDO), the founding members, promote dioxygenation through a two-step monooxygenation pathway. However, the new members of the superfamily, including PrnB, SfmD, TyrH, and MarE, expand its boundaries and mediate monooxygenation on a broader set of aromatic substrates. We found that the enlarged superfamily contains eight clades of proteins. Overall, this protein group is a more sizeable, structure-based, histidine-ligated heme-dependent, and functionally diverse superfamily for aromatics oxidation. The concept of TDO superfamily or heme-dependent dioxygenase superfamily is no longer appropriate for defining this growing superfamily. Hence, there is a pressing need to redefine it as a heme-dependent aromatic oxygenase (HDAO) superfamily. The revised concept puts HDAO in the context of thiol-ligated heme-based enzymes alongside cytochrome P450 and peroxygenase. It will update what we understand about the choice of heme axial ligand. Hemoproteins may not be as stringent about the type of axial ligand for oxygenation, although thiolate-ligated hemes (P450s and peroxygenases) more frequently catalyze oxygenation reactions. Histidine-ligated hemes found in HDAO enzymes can likewise mediate oxygenation when confronted with a proper substrate.
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http://dx.doi.org/10.1073/pnas.2106561118DOI Listing
October 2021

bFGF could be a biomarker of malignancy in RSPE syndrome: an ambispective single-center cohort analysis of 51 patients.

Arthritis Res Ther 2021 10 15;23(1):261. Epub 2021 Oct 15.

Department of Rheumatology & Immunology and Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, China.

Objectives: Remitting seronegative symmetrical synovitis with pitting edema (RSPE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RSPE.

Methods: A total of 51 patients with RSPE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy.

Results: A total of forty-eight RSPE patients (94.1%) were available with follow-up data; 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor; and 2 patients were solid tumors. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RSPE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RSPE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL], and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RSPE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RSPE.

Conclusions: This study indicated that bFGF was elevated in RSPE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RSPE.
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http://dx.doi.org/10.1186/s13075-021-02638-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518293PMC
October 2021

Eco-green C, O co-doped porous BN adsorbent for aqueous solution with superior adsorption efficiency and selectivity.

Chemosphere 2021 Oct 8;288(Pt 2):132520. Epub 2021 Oct 8.

School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130, PR China; Hebei Key Laboratory of Boron Nitride Micro and Nano Materials, Hebei University of Technology, Tianjin, 300130, PR China. Electronic address:

Toxic dyes in wastewater will become a significant hazard to human health if they are not treated effectively. Therefore, it is significant to separate and remove dyes from the aqueous solution. C and O co-doped BN (BCNO) with high adsorption capacity and outstanding cycle efficiency is a simple and efficient adsorbent for the cationic dye malachite green (MG). Glucose is characterized as an eco-friendly and cheap source of C and O. Benefited by the high specific surface area (1515.6 m/g), the maximum adsorption capacity of MG is 1511.1 mg/g. Besides, the curves of adsorption fitting correspond to the Langmuir model and the pseudo-second-order model, respectively. Moreover, after 5 cycles, the adsorption efficiency reached 78% of the first time and the adsorption capacity remained above 780 mg/g. Furthermore, in the selectivity adsorption study, the cationic dyes (MG, neutral red (NR), methylene blue (MB)) can be removed more effectively in the binary dye system of MG-methyl orange (MO), NR-MO, MB-MO, MG-Orange II (OR), MB-OR, or NR-OR. BCNO-2 has a promising application in the removal of cationic dyes from complex dye wastewaters.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132520DOI Listing
October 2021

Ontogenetic moulting behavior of the Cambrian oryctocephalid trilobite .

PeerJ 2021 23;9:e12217. Epub 2021 Sep 23.

College of Resources and Environmental Engineering, Key Laboratory of Karst Georesources and Environment, Ministry of Education, Guizhou University, Guiyang, Guizhou Province, China.

Moulting behaviors in trilobites are a crucial strategy during development. Previous studies have demonstrated inter-and intraspecific variability of moulting behavior in trilobites. Currently, ecdysial motifs for trilobites are considered not stable even within species and fewer detailed studies dealt with moulting behaviors in a single species of trilobite during development. Here a large sample of meraspid to holaspid exuviae of (131 specimens) from the Cambrian Balang Formation of South China has allowed description of the reasonably complete ontogenic moulting sequence. Both ontogenetic stage and body size reveal gradual transition of configuration from Somersault configuration to Henningsmoen's configuration during development. Somersault configuration is exclusive till meraspid degree five and exists in subsequent growth stages. This suggests that opening of the facial and rostral sutures allowing the emergence forward of the post-ecdysial trilobite was prevalent in early growth stages. In later development, Henningsmoen's configuration (showing disarticulation of the cranidium) became more dominant. This study indicates that gradual transition of ontogenetic moulting behavior occurred in oryctocephalid trilobites in the early Cambrian.
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http://dx.doi.org/10.7717/peerj.12217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465991PMC
September 2021

Physiological and transcriptomic analyses of the effects of exogenous melatonin on drought tolerance in maize (Zea mays L.).

Plant Physiol Biochem 2021 Oct 5;168:128-142. Epub 2021 Oct 5.

College of Agronomy, Northwest A&F University, Yangling Shaanxi, 712100, China. Electronic address:

Water deficit inhibits maize (Zea mays L.) seedling growth and yield. Application of exogenous melatonin can improve drought tolerance of corn, but little is known regarding the transcriptional mechanisms of melatonin-mediated drought tolerance in maize. Increased understanding of the effects of melatonin on maize plants under drought stress is vital to alleviate the adverse effects of drought on food production in the future. The aim of this investigation was to use physiological and transcriptome analyses for exploring the possible mechanisms of exogenous melatonin against drought stress in maize. In this study, maize seedlings were subjected to drought stress and some were treated with exogenous melatonin. The physiological results showed that melatonin inhibited HO accumulation and promoted the scavenging of excessive reactive oxygen species to reduce oxidative damage in maize leaves. Transcriptomic analysis identified 957 differentially expressed genes between melatonin and non-melatonin treatment groups. Further detailed analyses suggested that melatonin-regulated genes are mainly related to glutathione metabolism, calcium signaling transduction, and jasmonic acid biosynthesis. Some transcription factor families, such as WRKY, AP2/ERF-ERF, MYB, NAC, and bZIP, were also activated by exogenous melatonin. Moreover, crosstalk between melatonin and other hormones that mediate drought tolerance was observed. In conclusion, the combination of physiological and transcriptome analyses revealed some mechanisms underlying the role of melatonin in alleviating drought; knowledge of these mechanisms may assist in successful maize cultivation under drought stress.
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http://dx.doi.org/10.1016/j.plaphy.2021.09.044DOI Listing
October 2021

[email protected] Nanoclusters Potentiate Efficacy of Cancer Immunotherapy.

Adv Mater 2021 Oct 7:e2104037. Epub 2021 Oct 7.

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.

Although immunotherapy such as immune checkpoint inhibitors has shown promising efficacy in cancer treatment, the responsiveness among patients is relatively limited. Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity has become an emerging strategy for enhancing tumor immunotherapy. Herein, [email protected] (bovine serum albumin) nanoclusters synthesized via a self-assembly approach are reported, where the released zinc ions under acidic tumor microenvironment significantly enhance cGAS/STING signals. Meanwhile, intracellular zinc ions can produce reactive oxygen species, which is further facilitated by the generated H S gas from [email protected] via specifically inhibiting catalase in hepatocellular carcinoma cells. It is found that the nanoclusters activate the cGAS/STING signals in mice, which promotes the infiltration of CD8 T cells at the tumor site and cross-presentation of dendritic cells, leading to an improved immunotherapy efficacy against hepatocellular carcinoma.
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http://dx.doi.org/10.1002/adma.202104037DOI Listing
October 2021

Low-Dose Interleukin-2 as an Alternative Therapy for Refractory Lupus Nephritis.

Rheumatol Ther 2021 Oct 7. Epub 2021 Oct 7.

Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South street, Beijing, 100044, China.

Introduction: Low-dose interleukin-2 (IL-2) selectively restores disturbances of regulatory T cells (Treg) and conventional T cells, resulting in the induction of remission in patients with systemic lupus erythematosus. However, to date no research has been carried out on the efficacy of low-dose IL-2 in the treatment of refractory lupus nephritis (LN). The aim of the study reported here was to investigate the renal response to low-dose IL-2 in patients with refractory LN.

Methods: The study population comprised ten patients with refractory LN who failed to achieve complete response or who had relapsed while being treated with at least two conventional immunosuppressive agents. One treatment cycle consisted of IL-2 at a dose of 1 million IU administered subcutaneously every other day for 2 weeks followed by a 2-week break. All patients received three cycles of IL-2 and were then followed up for another 12 weeks without any increase in the dose of previous immunosuppressive agents and steroids.

Results: Of the ten patients enrolled in the study, seven (70%) achieved ≥ 50% improvement in proteinuria at 12 weeks after initiating treatment with IL-2. Median proteinuria was significantly reduced by 50.3% at week 12, from 1.83 (interquartile range [IQR] 1.23-3.21)  g/24 h at baseline to 0.91 (IQR 0.52-1.60)  g/24 h at 12 weeks (P = 0.005). This was accompanied by a 71% reduction in urine erythrocytes, from 64/µl (IQR 24-102/µl) at baseline to 18/µl (IQR 2-20/µl) at 12 weeks (P = 0.018). Anti-dsDNA was decreased from 27.9 (IQR 7.6-40.28) IU/ml at baseline to 14.1 (IQR 7.3-20.12) IU/ml (P = 0.021) at week 12, while complements C3 and C4 were slightly increased (P = 0.445, P = 0.241, respectively). A significant expansion of Treg cells, from 9.3% at baseline to 16.6% at 12 weeks, was also found (P < 0.05). No serious adverse events occurred during the treatment period.

Conclusions: Low-dose IL-2 therapy may have a promising role in the treatment of refractory LN as an alternative and safe therapeutic approach. It may be used as multi-target combination therapy in clinical practice.
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http://dx.doi.org/10.1007/s40744-021-00381-1DOI Listing
October 2021

An Automatic Knee Osteoarthritis Diagnosis Method Based on Deep Learning: Data from the Osteoarthritis Initiative.

J Healthc Eng 2021 27;2021:5586529. Epub 2021 Sep 27.

National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Osteoarthritis (OA) is the most common form of arthritis. According to the evidence presented on both sides of the knee bones, radiologists assess the severity of OA based on the Kellgren-Lawrence (KL) grading system. Recently, computer-aided methods are proposed to improve the efficiency of OA diagnosis. However, the human interventions required by previous semiautomatic segmentation methods limit the application on large-scale datasets. Moreover, well-known CNN architectures applied to the OA severity assessment do not explore the relations between different local regions. In this work, by integrating the object detection model, YOLO, with the visual transformer into the diagnosis procedure, we reduce human intervention and provide an end-to-end approach to automatic osteoarthritis diagnosis. Our approach correctly segments 95.57% of data at the expense of training on 200 annotated images on a large dataset that contains more than 4500 samples. Furthermore, our classification result improves the accuracy by 2.5% compared to the traditional CNN architectures.
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http://dx.doi.org/10.1155/2021/5586529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490030PMC
September 2021

Adequate Silicone Oil Tamponade by Utilizing the Space of Anterior Segment for Complicated Retinal Detachment: Technique, Efficacy, and Safety.

Asia Pac J Ophthalmol (Phila) 2021 Sep 26. Epub 2021 Sep 26.

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China.

Purpose: To evaluate the efficacy and safety of adequate silicone oil (SO) tamponade procedure in patients with complicated retinal detachment.

Methods: Thirty-one eyes in 31 patients were enrolled in this prospective case series. Adequate SO tamponade was performed by injecting the SO into the vitreous cavity and the entire anterior chamber, followed by posterior capsulotomy and inferior peripheral iridotomy. Preoperative and follow-up data including retinal anatomic reattachment and SO status, best-corrected visual acuity, intraocular pressure, surgical complications and management were collected and analyzed.

Results: Twenty-nine eyes presented with complete retinal reattachment after subsequent SO removal with a primary success rate of 93.5%. Seventeen patients (54.8%) had complete anterior chamber SO migration to the vitreous cavity within the first postoperative day. The average time for anterior chamber SO migration was 2.3 ± 1.8 days. No oil-fluid interface in the vitreous cavity was observed in all the eyes, indicating a relatively adequate SO tamponade. Acute intraocular pressure elevation occurred in 16 (51.6%) eyes and was controllable under medication (n = 16) and anterior chamber paracentesis (n = 1). Two patients developed recurrent retinal detachment and received SO removal and a secondary adequate SO tamponade. At final follow-up, all the eyes had SO removal for at least 3 months and retinas maintained completely attached.

Conclusions: The adequate SO tamponade procedure offers a simple, safe, and efficacious treatment alternative for complicated retinal detachment.
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http://dx.doi.org/10.1097/APO.0000000000000436DOI Listing
September 2021

The Euscaphis japonica genome and the evolution of malvids.

Plant J 2021 Sep 29. Epub 2021 Sep 29.

College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Malvids is one of the largest clades of rosids and include 58 families and exhibit remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from ILS and hybridization event during the diversification of the ancestral population of malvids. E. japonica experienced two polyploidisation events: the ancient whole genome triplication event (WGT) shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event (WGD), unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. A total of 1,012 candidate positively selected genes (PSGs) in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence, and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.
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http://dx.doi.org/10.1111/tpj.15518DOI Listing
September 2021

Genome-wide identification of soybean Shaker K channel gene family and functional characterization of GmAKT1 in transgenic Arabidopsis thaliana under salt and drought stress.

J Plant Physiol 2021 Nov 22;266:153529. Epub 2021 Sep 22.

College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, Jilin, 130118, China; College of Tropical Crops, Hainan University, Haikou, 570228, China. Electronic address:

Potassium is a major cationic nutrient involved in numerous physiological processes in plants. The uptake of K is mediated by K channels and transporters, and the Shaker K channel gene family plays an essential role in K uptake and stress resistance in plants. However, little is known regarding this family in soybean. In this study, 14 members of the Shaker K channel gene family were identified in soybean and were classified into five groups. Protein domain analysis revealed that Shaker K channel gene members have an ion transport domain (ion trans), a cyclic nucleotide-binding domain, ankyrin repeat domains, and a dimerization domain in the potassium ion channel. Quantitative real-time polymerase chain reaction analysis indicated that the expression of eight genes (notably GmAKT1) in soybean leaves and roots was significantly increased in response to salt and drought stress. Furthermore, the overexpression of GmAKT1 in Arabidopsis enhanced root length, K concentration, and fresh/dry weight ratio compared with wild-type plants subjected to salt and drought stress; this suggests that GmAKT1 improves the tolerance of soybean to abiotic stress. Our results provide important insight into the characterization of Shaker K channel gene family members in soybean and highlight the function of GmAKT1 in soybean plants under salt and drought stress.
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http://dx.doi.org/10.1016/j.jplph.2021.153529DOI Listing
November 2021

Oncology clinic-based germline genetic testing for exocrine pancreatic cancer enables timely return of results and unveils low uptake of cascade testing.

J Med Genet 2021 Sep 23. Epub 2021 Sep 23.

Department of Surgery, McGill University, Montreal, Québec, Canada

Background: Traditional medical genetics models are unable to meet the growing demand for germline genetic testing (GT) in patients with exocrine pancreatic cancer (PC). This study investigates the impact of an ambulatory oncology clinic-based GT model.

Methods: From 2012 to 2021, patients with PC were prospectively enrolled and considered for GT. Two chronological cohorts were compared: (1) the preuniversal genetic testing (pre-UGT) cohort, which received GT based on clinical criteria or family history; and (2) the post-UGT cohort, where an 86-gene panel was offered to all patients with PC.

Results: Of 847 eligible patients, 735 (86.8%) were enrolled (pre-UGT, n=579; post-UGT, n=156). A higher proportion of the post-UGT cohort received prospective GT (97.4% vs 58.5%, p<0.001). The rate of pathogenic germline alterations (PGA) across both cohorts was 9.9%, with 8.0% of PGAs in PC susceptibility genes. The post-UGT cohort had a higher prevalence of overall PGAs (17.2% vs 6.6%, p<0.001) and PGAs in PC susceptibility genes (11.9% vs 6.3%, p<0.001). The median turnaround time from enrolment to GT report was shorter in the post-UGT cohort (13 days vs 42 days, p<0.001). Probands with a PGA disclosed their GT results to 84% of their first-degree relatives (FDRs). However, only 31% of informed FDRs underwent GT, and the number of new cases per index case was 0.52.

Conclusion: A point-of-care GT model is feasible and expedites access to GT for patients with PC. Strategies to increase the uptake of cascade testing are needed to maximise the clinical impact of an oncology clinic-based GT model.
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http://dx.doi.org/10.1136/jmedgenet-2021-108054DOI Listing
September 2021

Transparent qubit manipulations with spin-orbit coupled two-electron nanowire quantum dot.

Sci Rep 2021 Sep 22;11(1):18839. Epub 2021 Sep 22.

Department of Physics and Key Laboratory of Low Dimensional Quantum Structures and Quantum Control of Ministry of Education, Hunan Normal University, Changsha, 410081, China.

We report on the first set of exact orthonormalized states to an ac driven one-dimensional (1D) two-electron nanowire quantum dot with the Rashba-Dresselhaus coexisted spin-orbit coupling (SOC) and the controlled magnetic field orientation and trapping frequency. In the ground state case, it is shown that the spatiotemporal evolutions of probability densities occupying internal spin states and the transfer rates between different spin states can be adjusted by the ac electric field and the intensities of SOC and magnetic field. Effects of the system parameters and initial-state-dependent constants on the mean entanglement are revealed, where the approximately maximal entanglement associated with the stronger SOC and its insensitivity to the initial and parametric perturbations are demonstrated numerically. A novel resonance transition mechanism is found, in which the ladder-like time-evolution process of expected energy and the transition time between two arbitrary exact states are controlled by the ac field strength. Using such maximally entangled exact states to encode qubits can render the qubit control more transparent and robust. The results could be extended to 2D case and to an array of two-electron quantum dots with weak neighboring coupling for quantum information processing.
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http://dx.doi.org/10.1038/s41598-021-98152-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458319PMC
September 2021

Real-time dynamics and structures of supported subnanometer catalysts via multiscale simulations.

Nat Commun 2021 Sep 14;12(1):5430. Epub 2021 Sep 14.

Department of Chemical and Biomolecular Engineering, 150 Academy St., University of Delaware, Newark, Delaware, DE, 19716, United States.

Understanding the performance of subnanometer catalysts and how catalyst treatment and exposure to spectroscopic probe molecules change the structure requires accurate structure determination under working conditions. Experiments lack simultaneous temporal and spatial resolution and could alter the structure, and similar challenges hinder first-principles calculations from answering these questions. Here, we introduce a multiscale modeling framework to follow the evolution of subnanometer clusters at experimentally relevant time scales. We demonstrate its feasibility on Pd adsorbed on CeO(111) at various catalyst loadings, temperatures, and exposures to CO. We show that sintering occurs in seconds even at room temperature and is mainly driven by free energy reduction. It leads to a kinetically (far from equilibrium) frozen ensemble of quasi-two-dimensional structures that CO chemisorption and infrared experiments probe. CO adsorption makes structures flatter and smaller. High temperatures drive very rapid sintering toward larger, stable/metastable equilibrium structures, where CO induces secondary structure changes only.
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http://dx.doi.org/10.1038/s41467-021-25752-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440615PMC
September 2021

Integrated farming with intercropping increases food production while reducing environmental footprint.

Proc Natl Acad Sci U S A 2021 Sep;118(38)

Agriculture and Agri-Food Canada, Swift Current Research and Development Centre, Swift Current, SK S9H 3X2, Canada

Food security has been a significant issue for the livelihood of smallholder family farms in highly populated regions and countries. Industrialized farming in more developed countries has increased global food supply to meet the demand, but the excessive use of synthetic fertilizers and pesticides has negative environmental impacts. Finding sustainable ways to grow more food with a smaller environmental footprint is critical. We developed an integrated cropping system that incorporates four key components: 1) intensified cropping through relay planting or intercropping, 2) within-field strip rotation, 3) soil mulching with available means, such as crop straw, and 4) no-till or reduced tillage. Sixteen field experiments, conducted with a wide range of crop inputs over 12 consecutive years (2006 to 2017), showed that the integrated system with intercropping generates significant synergies-increasing annual crop yields by 15.6 to 49.9% and farm net returns by 39.2% and decreasing the environmental footprint by 17.3%-when compared with traditional monoculture cropping. We conclude that smallholder farmers can achieve the dual goals of growing more food and lowering the environmental footprint by adopting integrated farming systems.
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http://dx.doi.org/10.1073/pnas.2106382118DOI Listing
September 2021

Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1.

J Cell Mol Med 2021 Oct 12;25(19):9319-9330. Epub 2021 Sep 12.

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Long non-coding RNA DLX6 antisense RNA 1 (DLX6-AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6-AS1, microRNA (miR)-193b-3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6-AS1/miR-193b-3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6-AS1, miR-193b-3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6-AS1/miR-193b-3p-related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6-AS1 and HOXA1 were up-regulated, and miR-193b-3p was down-regulated in TC. Depleted DLX6-AS1 or restored miR-193b-3p disturbed cell growth and promoted autophagy. DLX6-AS1 targeted miR-193b-3p and positively regulated HOXA1. miR-193b-3p inhibition mitigated the impaired tumorigenesis induced by down-regulated DLX6-AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6-AS1 depletion hinders TC cell growth and promotes autophagy via up-regulating miR-193b-3p and down-regulating HOXA1.
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http://dx.doi.org/10.1111/jcmm.16868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500975PMC
October 2021

Crystal structure of human cysteamine dioxygenase provides a structural rationale for its function as an oxygen sensor.

J Biol Chem 2021 Sep 8;297(4):101176. Epub 2021 Sep 8.

Department of Chemistry, The University of Texas at San Antonio, Texas, USA. Electronic address:

Cysteamine dioxygenase (ADO) plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis in humans by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O as a cosubstrate. However, as the only thiol dioxygenase that processes both small-molecule and protein substrates, how ADO handles diverse substrates of disparate sizes to achieve various reactions is not understood. The knowledge gap is mainly due to the three-dimensional structure not being solved, as ADO cannot be directly compared with other known thiol dioxygenases. Herein, we report the first crystal structure of human ADO at a resolution of 1.78 Å with a nickel-bound metal center. Crystallization was achieved through both metal substitution and C18S/C239S double mutations. The metal center resides in a tunnel close to an entry site flanked by loops. While ADO appears to use extensive flexibility to handle substrates of different sizes, it also employs proline and proline pairs to maintain the core protein structure and to retain the residues critical for catalysis in place. This feature distinguishes ADO from thiol dioxygenases that only oxidize small-molecule substrates, possibly explaining its divergent substrate specificity. Our findings also elucidate the structural basis for ADO functioning as an oxygen sensor by modifying N-degron substrates to transduce responses to hypoxia. Thus, this work fills a gap in structure-function relationships of the thiol dioxygenase family and provides a platform for further mechanistic investigation and therapeutic intervention targeting impaired oxygen sensing.
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http://dx.doi.org/10.1016/j.jbc.2021.101176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503633PMC
September 2021

Tetrahydropalmatine attenuates MSU crystal-induced gouty arthritis by inhibiting ROS-mediated NLRP3 inflammasome activation.

Int Immunopharmacol 2021 Nov 3;100:108107. Epub 2021 Sep 3.

The First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210029, PR China. Electronic address:

Activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory responses of monosodium urate (MSU) crystal-induced gouty arthritis. Therefore, the molecular basis of NLRP3 inflammasome is very valuable in developing potential therapeutic drugs for gout. Tetrahydropalmatine (THP), the main active component of the traditional Chinese medicinal herb Corydalis yanhusuo, has shown prominent anti-inflammatory and analgesic activities, but to date, these effects have not been investigated exhaustively on gout. This study indicated that THP attenuated pain and swelling in an MSU-induced acute gout model by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration. THP exerted its actions by suppressing NLRP3 inflammasome activation and subsequent formation of caspase-1. Furthermore, results showed that THP alleviated MSU-induced reactive oxygen species (ROS) generation, upstream of NLRP3 inflammasome activation, by an increase in the activities of antioxidant enzymes both in vitro and in vivo. In conclusion, our study suggests that THP suppressed ROS-mediated NLRP3 inflammasome activation in MSU-induced inflammatory responses, which highlights its therapeutic potential in gouty arthritis.
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http://dx.doi.org/10.1016/j.intimp.2021.108107DOI Listing
November 2021

TNFAIP3-upregulated RIP3 exacerbates acute pancreatitis via activating NLRP3 inflammasome.

Int Immunopharmacol 2021 Nov 1;100:108067. Epub 2021 Sep 1.

Department of Emergency Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, PR China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, PR China. Electronic address:

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Accumulating studies have revealed the involvement of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) in the progression of AP. Here, the current study was conducted to elucidate the role of TNFAIP3 and the underlying molecular mechanisms on the progression of AP. The in vivo animal model and in vitro cell model of AP were generated by retrograde injection of sodium taurocholate and stimulation of cerulein into AR42J cells, respectively. Relationships among TNFAIP3, receptor interacting protein 3 (RIP3) and nod-like receptor protein 3 (NLRP3) were predicted on bioinformatics websites and verified by co-immunoprecipitation. AR42J cells were transfected with overexpressing plasmid or shRNA to study the effects of TNFAIP3/RIP3/NLRP3 axis on cell proliferation and apoptosis, secretion of inflammatory cytokines and production of ROS. The effect of TNFAIP3/RIP3/NLRP3 axis in AP was further confirmed in vivo. High expression of TNFAIP3 was observed in AP pancreatic tissues and AP cell model. TNFAIP3 increased RIP phosphorylation through deubiquitination. RIP activated the NLRP3 inflammasome. Silencing of TNFAIP3 or RIP3T led to elevated proliferation and inhibited apoptosis in AR42J cells, accompanied by decreased inflammatory cytokine levels and ROS production. The protective role of inhibited TNFAIP3 in AP was confirmed evidenced by reduced levels of AMY, LIPA, and ROS in vivo. Collectively, overexpressed TNFAIP3 could contribute to the progression of AP by activating RIP3/NLRP3 axis, providing a potential therapeutic target for AP treatment.
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http://dx.doi.org/10.1016/j.intimp.2021.108067DOI Listing
November 2021

Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer.

J Hematol Oncol 2021 08 30;14(1):134. Epub 2021 Aug 30.

Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies globally. Despite aggressive and multimodal treatment regimens, the overall survival of HCC patients remains poor. MAIN: Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with covalently closed structures and tissue- or organ-specific expression patterns in eukaryotes. They are highly stable and have important biological functions, including acting as microRNA sponges, protein scaffolds, transcription regulators, translation templates and interacting with RNA-binding protein. Recent advances have indicated that circRNAs present abnormal expression in HCC tissues and that their dysregulation contributes to HCC initiation and progression. Furthermore, researchers have revealed that some circRNAs might serve as diagnostic biomarkers or drug targets in clinical settings. In this review, we systematically evaluate the characteristics, biogenesis, mechanisms and functions of circRNAs in HCC and further discuss the current shortcomings and potential directions of prospective studies on liver cancer-related circRNAs.

Conclusion: CircRNAs are a novel class of ncRNAs that play a significant role in HCC initiation and progression, but their internal mechanisms and clinical applications need further investigation.
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http://dx.doi.org/10.1186/s13045-021-01145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407006PMC
August 2021

Source-specific risk apportionment and critical risk source identification of antibiotic resistance in Fenhe River basin, China.

Chemosphere 2021 Aug 25;287(Pt 1):131997. Epub 2021 Aug 25.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, No. 19, Xinjiekouwai Street, Beijing, 100875, China.

A comprehensive understanding of the sources and distribution of antibiotic resistance risk is essential for controlling antibiotic pollution and resistance. Based on surface water samples collected from the Fenhe River basin in the flood season, using the positive matrix factorization (PMF) model, the risk quotient (RQ) method and the multiple attribute decision making (MADM) method, the resistance risk and source-specific resistance risk of antibiotics were analyzed in this study. The results showed that sulfonamides (SAs) were the dominant antibiotics with a mean concentration of 118.30 ng/L, whereas tetracyclines (TCs) and macrolides (MLs) had the highest detection frequencies (100%). The significant resistance risk rate of antibiotics in the entire river basin was 48%, but no high risk occurred. The significant resistance risk rate of quinolones (QNs) was the highest (100%), followed by that of MLs and TCs. Owing to human activities, the most serious resistance risk occurred in the midstream of the river basin. The resistance risk was the lowest upstream. The antibiotics were mainly contributed by six sources. Pharmaceutical wastewater was the main source, accounting for 30%, followed by livestock discharge (22%). The resistance risk from the six sources showed clear differences, but none of the sources caused a high risk of antibiotic resistance. Pharmaceutical wastewater poses the greatest risk of antibiotic resistance in the Fenhe River basin and is widely distributed. The second greatest source was livestock discharge, which was mainly concentrated in the upstream and midstream areas. The critical sources upstream, midstream, and downstream were all pharmaceutical wastewater, whereas the sequences of other sources were different because different areas were affected by different human activities. The proposed method might provide an important reference for the identification the key source of antibiotics and management of antibiotic pollution, as well as help for the management of antibiotics in Fenhe and Shanxi Province.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131997DOI Listing
August 2021

Dendrite-Free and Ultra-Long-Life Lithium Metal Anode Enabled via a Three-Dimensional Ordered Porous Nanostructure.

ACS Appl Mater Interfaces 2021 Sep 26;13(35):41744-41752. Epub 2021 Aug 26.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Constructing a stable non-dendritic lithium metal anode is the key to the development of high-energy batteries in the future. Herein, we fabricated nitrogen-doped carbon photonic crystals in situ in the macropores of carbon papers as a porous skeleton and confined hosts for metallic lithium. The large specific surface area of the carbon photonic crystal reduces the current density of the electrode. The three-dimensional ordered microstructure promotes uniform charge distribution and uniform lithium deposition and inhibits the volume expansion of metallic lithium. The as-prepared lithium metal anode exhibits prominent electrochemical performance with a small hysteresis of less than 95 mV beyond 180 cycles at an extremely high current density of 15 mA cm. When the as-prepared lithium metal anode is coupled with the sulfur cathode, the obtained full cell displays enhanced capacitive properties and cycle life. Compared with the bare Li anode, the full cell exhibits more than 300 cycles of cell life and a 70 mA h g higher discharge capacity.
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http://dx.doi.org/10.1021/acsami.1c12576DOI Listing
September 2021

Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in China.

Thromb Haemost 2021 Aug 24. Epub 2021 Aug 24.

Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Objective:  This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events.

Methods:  Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events.

Results:  Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.92 ± 9.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65-1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91-1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53-1.23) between the clopidogrel- and ticagrelor-treated groups.

Conclusion:  In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.
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http://dx.doi.org/10.1055/s-0041-1735193DOI Listing
August 2021
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