Publications by authors named "Lei Zhu"

1,657 Publications

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Chemotherapy Combined With Recombinant Human Endostatin (Endostar) Significantly Improves the Progression-Free Survival of Stage IV Soft Tissue Sarcomas.

Front Oncol 2021 3;11:778774. Epub 2022 Jan 3.

Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Purpose: Our previously study showed that recombinant human endostatin (Endostar) combined with chemotherapy had significant activity to increase the mPFS in patients with advanced sarcomas with tolerable side effects. However, the small cohort size and short follow-up time made it difficult to screen sensitive sarcoma subtypes and determine whether there is an overall survival benefit. With the largest sarcoma cohort to our knowledge, we try to confirm the efficacy and safety of chemotherapy combined with Endostar in stage IV sarcomas, with the specific purpose of finding out the sensitive sarcoma types for this combined treatment.

Methods: After the exclusion of ineligible patients, 156 patients with stage IV bone and soft tissue sarcomas were included in this study according to the inclusion criteria.

Results: By the end of follow-up, the ORR was 10.7% (9/84) vs 1.4% (1/72) (p=0.041), the DCR was 26.2% (22/84) vs 5.6% (4/72) (p=0.001) in the combined group and chemotherapy group, respectively. The mPFS of combined group was significantly longer than the chemotherapy group (10.42 vs 6.87 months, p=0.003). The mOS were 26.84 months and 23.56 months, without significant difference (p= 0.481). In osteogenic sarcoma, there was no statistically significant difference in the mPFS between the two groups (p=0.59), while in the soft tissue sarcoma, the mPFS in the combined group was significantly higher than that of the chemotherapy group (11.27 vs 8.05 months, p=0.004). Specifically, undifferentiated polymorphic sarcoma (UPS) was the possible sarcoma subtypes that benefited from the combined therapy. For the 38 UPS patients (28 patients in the combined group and 10 patients in the chemotherapy group), the mPFS in the combined group was up to 14.88 months, while it was only 7.1 months in the chemotherapy group, with a significant difference (p=0.006). The most common adverse events in the combined group were myelosuppression, gastrointestinal reactions and abnormal liver function, without significant difference in two groups.

Conclusion: Chemotherapy plus Endostar could prolong mPFS and improve ORR and DCR in patients with stage IV soft tissue sarcoma, suggesting that the combined therapy could improve the patient prognosis in soft tissue sarcomas, especially the UPS patients.
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http://dx.doi.org/10.3389/fonc.2021.778774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761904PMC
January 2022

Does erythropoietin affect the outcome and complication rates of patient with traumatic brain injury? A pooled-analysis.

Neurol Sci 2022 Jan 19. Epub 2022 Jan 19.

Institute of Public Health, Medical College, Yangzhou University, Yangzhou, China.

Objective: The aim of this meta-analysis was to review the scientific literature published until April 18, 2021, to summarize existing knowledge on the efficacy and safety of erythropoietin (EPO) for traumatic brain injury (TBI).

Methods: This systematic review followed PRISMA guidelines. Randomized controlled trials (RCTs) reporting on the efficacy and safety of EPO in the treatment of TBI were systematically searched in relevant electronic databases according to a pre-designed search strategy. The primary outcomes are the mortality; and secondary outcomes are the good functional outcome (GFO) and adverse events (AEs).

Results: A total of 10 RCTs involving 2,402 participants fulfilled the inclusion criteria. The results showed that there is a significant difference in terms of the mortality (RR = 0.67, 95% CI = 0.54-0.84, P = 0.0003) and seizure rate (RR = 0.52, 95% CI = 0.29-0.96, P = 0.04) between the EPO groups compared to those in the control groups. However, compared with the control groups, the GFO in the EPO groups was not statistically significant (RR = 1.18, 95% CI = 0.93-1.48, P = 0.17).

Conclusions: Findings of the present meta-analysis suggest that the use of EPO could reduce mortality rate in patients with TBI, without increasing the incidence of AEs. EPO has potential research and application value in the treatment of TBI.
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http://dx.doi.org/10.1007/s10072-022-05877-4DOI Listing
January 2022

Treatment of Progressive Nodular Histiocytosis With Baricitinib.

JAMA Dermatol 2022 Jan 19. Epub 2022 Jan 19.

Dermatology Hospital, Southern Medical University, Guangzhou, China.

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http://dx.doi.org/10.1001/jamadermatol.2021.5579DOI Listing
January 2022

YB-1 recruits Drosha to promote splicing of pri-miR-192 to mediate the proangiogenic effects of HS.

Antioxid Redox Signal 2022 Jan 19. Epub 2022 Jan 19.

Fudan University School of Basic Medical Sciences, 58305, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai, China;

Aims: The genes targeted by miRNAs have been well studied. However, little is known about the feedback mechanisms to control the biosynthesis of miRNAs which are essential for the miRNA feedback networks in the cells. In this present study, we aimed to examine how hydrogen sulfide (H2S) promotes angiogenesis by regulating miR-192 biosynthesis.

Results: H2S promoted in vitro angiogenesis, and angiogenesis in Matrigel plugs embedded in mice by up-regulating miR-192. Knockdown of the H2S generating enzyme cystathionine γ-lyase (CSE) suppressed in vitro angiogenesis and this suppression was rescued by exogenous H2S donor NaHS. Plakophilin 4 (PKP4) served as a target gene of miR-192. H2S up-regulated miR-192 via the VEGFR2/Akt pathway to promote the splicing of primary miR-192 (pri-miR-192), and resulted in an increase in both the precursor- and mature forms of miR-192. H2S translocated YB-1 into the nuclei to recruit Drosha to bind with pri-miR-192 and promoted its splicing. NaHS treatment promoted angiogenesis in the hind-limb ischemia mouse model and the skin-wound-healing model in diabetic mice, with up-regulated miR-192 and down-regulated PKP4 upon NaHS treatment. In human atherosclerotic plaques, miR-192 levels were positively correlated with the plasma H2S concentrations. Innovation and conclusion: Our data reveal a role of YB-1 in recruiting Drosha to splice pri-miR-192 to mediate the pro-angiogenic effect of H2S. CSE/H2S/YB-1/Drosha/miR-192 is a potential therapeutic target pathway for treating diseases including organ ischemia and diabetic complications.
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http://dx.doi.org/10.1089/ars.2021.0105DOI Listing
January 2022

Absorption Enhancement of Black Carbon Aerosols Constrained by Mixing-State Heterogeneity.

Environ Sci Technol 2022 Jan 18. Epub 2022 Jan 18.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China.

Atmospheric black carbon (BC) has a large yet highly uncertain contribution to global warming. When mixed with non-BC/coating material during atmospheric aging, the BC light absorption can be enhanced through the lensing effect. Laboratory and modeling studies have consistently found strong BC absorption enhancement, while the results in ambient measurements are conflicting, with some reporting weak absorption enhancement even for particles with large bulk coating amounts. Here, from our direct field observations, we report both large and minor absorption enhancement factors for different BC-containing particle populations with large bulk non-BC-to-BC mass ratios. By gaining insights into the measured coating material distribution across each particle population, we find that the level of absorption enhancement is strongly dependent on the particle-resolved mixing state. Our study shows that the greater mixing-state heterogeneity results in the larger difference between observed and predicted absorption enhancement. We demonstrate that by considering the variability in coating material thickness in the optical model, the previously observed model measurement discrepancy of absorption enhancement can be reconciled. The observations and improved optical models reported here highlight the importance of mixing-state heterogeneity on BC's radiative forcing, which should be better resolved in large-scale models to increase confidence when estimating the aerosol radiation effect.
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http://dx.doi.org/10.1021/acs.est.1c06180DOI Listing
January 2022

The Application Value of ceMDCT in the Diagnosis of Gastric Cancer Extramural Vascular Invasion and Its Influencing Factors.

J Healthc Eng 2022 7;2022:4239600. Epub 2022 Jan 7.

Department of Gastrointestinal Surgery, The Second Hospital of Harbin Medical University, Harbin, China.

Objective: To investigate the value of enhanced multislice spiral CT (ceMDCT) in the diagnosis of extramural vascular invasion of gastric cancer and the influencing factors of extramural vascular invasion. There are different methods used in this paper.

Method: 131 patients with primary gastric cancer treated in our hospital from January 2017 to May 2019 were selected. All patients underwent surgical resection and ceMDCT examination before operation.

Result: There were 40 cases with extramural vascular invasion of gastric cancer by surgical pathological diagnosis. The kappa value of ceMDCT in diagnosing extramural vascular invasion of gastric cancer was 0.947, and the consistency was excellent. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were 100.00%, 96.70%, 93.02%, and 100.00%, respectively. The proportions of T3-T4, tumour diameter ≥5.0 cm, and growth pattern of proximal nodular + diffuse type in patients with gastric cancer extramural vascular invasion were 92.50%, 85.00%, and 65.00%, respectively, which were significantly higher than those in patients without extramural vascular invasion ( < 0.05). The logistic regression analysis results showed that T3-T4, tumour diameter ≥5.0 cm, proximal nodular + diffuse growth pattern were the risk factors for extrahepatic vascular invasion in gastric cancer (OR = 3.751, 2.901, and 3.367, < 0.05).

Conclusion: ceMDCT has good application value in diagnosing gastric cancer extramural vascular invasion. The occurrence of gastric cancer extramural vascular invasion is affected by T staging, tumour diameter, and tumour growth pattern.
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http://dx.doi.org/10.1155/2022/4239600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759867PMC
January 2022

Unfolded protein response alleviates acid-induced premature senescence by promoting autophagy in nucleus pulposus cells.

Cell Biol Int 2022 Jan 12. Epub 2022 Jan 12.

Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Acid-induced cellular senescence is a critical underlying mechanism of intervertebral disc (IVD) degeneration (IDD). Acid stimulation activates a variety of biological changes including autophagy, endoplasmic reticulum stress, and related unfolded protein response (UPR), which are important regulators of cellular senescence. However, the precise mechanism of acid-mediated UPR and autophagy in nucleus pulposus cell (NPC) senescence has not been fully elucidated. In this study, we used acid to mimic the acidic microenvironment of IVD, and rat NPCs were cultured with or without autophagy or UPR signaling small-interfering RNAs. The related proteins and genes were assessed by immunofluorescence staining assay, Western blot analyses, and quantitative real-time polymerase chain reaction to monitor the activation of these signals and classify the molecular mechanisms underlying the correlation between autophagy and UPR pathway. Cell cycle analyses, senescence-associated β-galactosidase staining, gene expression, and immunoblotting analyses were performed to observe NPC senescence. Results showed that acid stimulation not only induced NPC senescence, but also initiated UPR and autophagy. Silencing the binding immunoglobulin protein signaling of UPR or autophagy signaling promoted rat NPC senescence. Knock-down of the UPR also blocked NPC autophagy. Taken together, UPR inhibits NPC senescence under acidic condition by activating autophagy. Hence, UPR-dependent autophagy could be an effective biologic target for the treatment of IDD in the future.
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http://dx.doi.org/10.1002/cbin.11751DOI Listing
January 2022

Correlating Electronic Structure and Device Physics with Mixing Region Morphology in High-Efficiency Organic Solar Cells.

Adv Sci (Weinh) 2022 Jan 12:e2104613. Epub 2022 Jan 12.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.

The donor/acceptor interaction in non-fullerene organic photovoltaics leads to the mixing domain that dictates the morphology and electronic structure of the blended thin film. Initiative effort is paid to understand how these domain properties affect the device performances on high-efficiency PM6:Y6 blends. Different fullerenes acceptors are used to manipulate the feature of mixing domain. It is seen that a tight packing in the mixing region is critical, which could effectively enhance the hole transfer and lead to the enlarged and narrow electron density of state (DOS). As a result, short-circuit current (J ) and fill factor (FF) are improved. The distribution of DOS and energy levels strongly influences open-circuit voltage (V ). The raised filling state of electron Fermi level is seen to be key in determining device V . Energy disorder is found to be a key factor to energy loss, which is highly correlated with the intermolecular distance in the mixing region. A 17.53% efficiency is obtained for optimized ternary devices, which is the highest value for similar systems. The current results indicate that a delicate optimization of the mixing domain property is an effective route to improve the V , J , and FF simultaneously, which provides new guidelines for morphology control toward high-performance organic solar cells.
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http://dx.doi.org/10.1002/advs.202104613DOI Listing
January 2022

Osthole Blocks HMGB1 Release From the Nucleus and Confers Protective Effects Against Renal Ischemia-Reperfusion Injury.

Front Physiol 2021 22;12:735425. Epub 2021 Dec 22.

Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China.

Renal ischemia-reperfusion (IR) is one of the main causes of renal injury. In severe cases with serious consequences, IR-related renal damage progresses rapidly and can even lead to acute renal failure. Its clinical treatment is currently difficult. According to various studies at home and abroad, HMGB1 is released from the nucleus into the cytoplasm or extracellular space by damaged parenchymal cells during ischemia and hypoxia, and this plays an important role in the initiation of reperfusion injury as an early inflammatory factor and is closely related to the occurrence and development of renal diseases. In recent years, the protective effect of osthole on IR of tissues and organs has been a key topic among clinical researchers. Osthole can inhibit the inflammatory response, reduce cell apoptosis the progression, and improve the prognosis of IR, thus protecting the kidney. During the development of renal IR, finding a mechanism through which the osthole blocks the release of HMGB1 from the nucleus would be helpful in detecting targets for clinical treatment.
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http://dx.doi.org/10.3389/fphys.2021.735425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727455PMC
December 2021

Smoking cessation rate and factors affecting the success of quitting in a smoking cessation clinic using telephone follow-up.

Tob Induc Dis 2021 20;19:99. Epub 2021 Dec 20.

Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha City, China.

Introduction: China has the largest number of smokers in the world. The great majority of China's smokers desire to quit smoking (QS); however, the success rate of self-quitting is low. This study investigated the effects of smoking cessation (SC) clinics in a cancer hospital in Hunan province and determined the influencing factors of successful SC.

Methods: Smokers were recruited to QS by healthcare workers in the SC clinic from February 2015 to February 2019. SC counseling was provided and telephone follow-up was conducted at 1 week, and at 1, 3 and 6 months. Patients who continued SC during the follow-up period were considered to have QS.

Results: Of the 344 patients included in this study, 16.3% QS at one week, 26.5% at one month, 27.6% at three months, and 31.7% at six months. Age ≥60 years, previous SC attempts, immediate quit dates, and telephone follow-up times (3-4 calls) were predictive factors for smokers to SC at six months.

Conclusions: Age, previous attempts to QS, immediate quit dates and telephone follow-up times were independent predictors of SC success at six months. SC clinics and frequent telephone follow-up improve the success rate of SC, especially in patients who have previously tried to QS or in those who set immediate quit dates.
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http://dx.doi.org/10.18332/tid/143375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686120PMC
December 2021

Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis.

Scand J Gastroenterol 2022 Jan 7:1-12. Epub 2022 Jan 7.

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Ulcerative colitis is a chronic recurrent intestinal inflammatory disease, and its recurrence is difficult to predict. In this review, we summarized the objective indicators that can be used to evaluate intestinal inflammation, the purpose is to better predict the clinical recurrence of UC, formulate individualized treatment plan during remission of UC, and improve the level of diagnosis and treatment of UC. Based on the search results in the PUBMED database, we explored the accuracy and value of these methods in predicting the clinical recurrence of UC from the following three aspects: endoscopic and histological scores, serum biomarkers and fecal biomarkers. Colonoscopy with biopsy is the gold standard for assessing intestinal inflammation, but it is invasive, inconvenient and expensive. At present, there is no highly sensitive and specific endoscopic or histological score to predict the clinical recurrence of UC. Compared with serum biomarkers, fecal biomarkers have higher sensitivity and specificity because they are in direct contact with the intestine and are closer to the site of intestinal inflammation. Fecal calprotectin is currently the most studied and meaningful fecal biomarker. Lactoferrin and S100A12, as novel biomarkers, have no better performance than FC in predicting the recurrence of UC. FC is currently the most promising predictive marker, but it lacks an accurate cut-off value. Combining patient symptoms, incorporating multiple indicators to construct a UC recurrence prediction model, and formulating individualized treatment plans for high recurrence risk patients will be the focus of UC remission management.
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http://dx.doi.org/10.1080/00365521.2021.2022193DOI Listing
January 2022

Boosting RGB-D Saliency Detection by Leveraging Unlabeled RGB Images.

IEEE Trans Image Process 2022 12;31:1107-1119. Epub 2022 Jan 12.

Training deep models for RGB-D salient object detection (SOD) often requires a large number of labeled RGB-D images. However, RGB-D data is not easily acquired, which limits the development of RGB-D SOD techniques. To alleviate this issue, we present a Dual-Semi RGB-D Salient Object Detection Network (DS-Net) to leverage unlabeled RGB images for boosting RGB-D saliency detection. We first devise a depth decoupling convolutional neural network (DDCNN), which contains a depth estimation branch and a saliency detection branch. The depth estimation branch is trained with RGB-D images and then used to estimate the pseudo depth maps for all unlabeled RGB images to form the paired data. The saliency detection branch is used to fuse the RGB feature and depth feature to predict the RGB-D saliency. Then, the whole DDCNN is assigned as the backbone in a teacher-student framework for semi-supervised learning. Moreover, we also introduce a consistency loss on the intermediate attention and saliency maps for the unlabeled data, as well as a supervised depth and saliency loss for labeled data. Experimental results on seven widely-used benchmark datasets demonstrate that our DDCNN outperforms state-of-the-art methods both quantitatively and qualitatively. We also demonstrate that our semi-supervised DS-Net can further improve the performance, even when using an RGB image with the pseudo depth map.
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http://dx.doi.org/10.1109/TIP.2021.3139232DOI Listing
January 2022

Bevacizumab in combination with paclitaxel and platinum for previously treated advanced thymic epithelial tumors.

Med Oncol 2022 Jan 4;39(2):25. Epub 2022 Jan 4.

Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, No. 241, West Huaihai Road, Shanghai, 200030, China.

There are no optimal regimens for advanced thymic epithelial tumors (TETs) when frontline chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with a routine chemotherapeutic regimen. Patients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160 mg/m) and cisplatin (70 mg/m) or carboplatin (area under the curve, 6) plus Bevacizumab (7.5 mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred. Between March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years). The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression-free survival for thymoma and thymic carcinoma was 6 and 8 months, respectively. Hematological toxicities were the main side effects. Paclitaxel and platinum plus Bevacizumab showed promising effects in refractory or relapsed advanced TETs without severe toxicity. Even when applied as salvage therapy, this regimen resulted in a better ORR than frontline chemotherapy.
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http://dx.doi.org/10.1007/s12032-021-01620-9DOI Listing
January 2022

Correlation between CT images of lateral plateau and lateral meniscus injuries in patients with Schatzker II tibial plateau fractures:a retrospective study.

BMC Musculoskelet Disord 2022 Jan 3;23(1). Epub 2022 Jan 3.

Department of Orthopedics, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu Province, 213000, China.

Background: There is a great deal of controversy on whether routine MRI examination is needed for fresh fractures while the vast majority of patients with tibial plateau fractures (TPFs) receive preoperative X-ray and CT examinations. The purpose of the study was to analyze the exact correlation between CT images of lateral plateau and lateral meniscus injuries in Schatzker II TPFs.

Methods: A total of 296 patients with Schatzker II TPFs from August 2012 to January 2021 in two trauma centers were enrolled for the analysis. According to the actual situation during open reduction internal fixation (ORIF) and knee arthroscopic surgery, patients were divided into meniscus injury (including rupture, incarceration, etc.) and non-meniscus injury groups. The values of both lateral plateau depression (LPD) and lateral plateau widening (LPW) of lateral tibial plateau on CT images were measured, and their correlation with lateral meniscus injury was then analyzed. The relevant receiver operating characteristic (ROC) curve was drawn to evaluate the optimal cut-off point of the two indicators which could predict meniscus injury.

Results: The intra- and inter-observer reliabilities of LPD and LPW were acceptable (intraclass correlation coefficient (ICC) > 0.8). The average LPD was 13.2 ± 3.2 mm while the average value of the group without meniscus injury was 9.4 ± 3.2 mm. The difference between the two groups was statistically significant (P < 0.05). The average LPW was 8.0 ± 1.4 mm and 6.8 ± 1.6 mm in meniscus injury and non-meniscus injury groups with a significant difference (P < 0.05). The optimal predictive cut-off value of LPD and LPW was 7.9 mm (sensitivity-95.0%, specificity-58.8%, area under the curve (AUC-0.818) and 7.5 mm (sensitivity-70.0%, specificity - 70.6%, AUC - 0.724), respectively. The meniscus injury group mainly showed injuries involving the mid-body and posterior horn of lateral meniscus (98.1%, 157/160).

Conclusions: The mid-body and posterior horn of lateral meniscus injury is more likely to occur in patients with Schatzker II TPFs when LPD > 7.9 mm and/or LPW > 7.5 mm on CT. These findings will definitely provide guidance for orthopedic surgeons in treating such injuries. During the operation, more attention is required be paid to the treatment of the meniscus and the possible fracture reduction difficulties and poor alignment caused by meniscus rupture and incarceration should be fully considered in order to achieve better surgical results.
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http://dx.doi.org/10.1186/s12891-021-04967-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725471PMC
January 2022

Targeted Gene Knockouts by Protoplast Transformation in the Moss .

Authors:
Lei Zhu

Front Genome Ed 2021 17;3:719087. Epub 2021 Dec 17.

Department of Botany and Plant Sciences, University of California, Riverside, CA, United States.

Targeted gene knockout is particularly useful for analyzing gene functions in plant growth, signaling, and development. By transforming knockout cassettes consisting of homologous sequences of the target gene into protoplasts, the classical gene targeting method aims to obtain targeted gene replacement, allowing for the characterization of gene functions . The moss is a known model organism for a high frequency of homologous recombination and thus harbors a remarkable rate of gene targeting. Other moss features, including easy to culture, dominant haploidy phase, and sequenced genome, make gene targeting prevalent in . However, even gene targeting was powerful to generate knockouts, researchers using this method still experienced technical challenges. For example, obtaining a good number of targeted knockouts after protoplast transformation and regeneration disturbed the users. Off-target mutations such as illegitimate random integration mediated by nonhomologous end joining and targeted insertion wherein one junction on-target but the other end off-target is commonly present in the knockouts. Protoplast fusion during transformation and regeneration was also a problem. This review will discuss the advantages and technical challenges of gene targeting. Recently, CRISPR-Cas9 is a revolutionary technology and becoming a hot topic in plant gene editing. In the second part of this review, CRISPR-Cas9 technology will be focused on and compared to gene targeting regarding the practical use in . This review presents an updated perspective of the gene targeting and CRISPR-Cas9 techniques to plant biologists who may consider studying gene functions in the model organism .
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http://dx.doi.org/10.3389/fgeed.2021.719087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718793PMC
December 2021

The Pedicled Flap of Adductor Longus, a New Technique for Inguinal Reconstruction.

Front Surg 2021 14;8:639893. Epub 2021 Dec 14.

Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.

Reconstruction surgeries of the inguinal area pose a challenge for oncological and orthopedic surgeons, especially after radical local resection (RLR), radical inguinal lymph node dissection (RILND), or both. Although numerous surgical procedures have been reported, there is no report about a pedicle adductor longus flap method. The aim of this work is to show our experience about inguinal reconstruction with pedicled adductor longus flap and associated outcomes. A retrospective study of 16 patients with localized inguinal region interventions and reconstructed by adductor longus flap from March 2016 to July 2020. Patients' average age was 60.0 years (range = 38-79 years) and had postoperative follow-up of 10 months (ranging 2-19 months). All patients had unilateral inguinal region involvement-seven cases on the left and nine cases on the right. The patients' clinical course, operative course, and postoperative follow-up data were evaluated. All 16 patients recovered well post-operatively and did not require any re-intervention. Four patients experienced negligible discomfort around the groin area. Five patients experienced a minor strength deficit in thigh adduction compared with that of preoperative strength in the same or contralateral leg. The aforementioned complications resolved during the postoperative course and had no functional impact on their activity of daily living. All adductor longus flaps survived, completely filled the inguinal dead space, and wounds healed uneventfully within 3 weeks except for three patients who suffered delayed wound healing for more than 4 weeks. Other common complications such as infection, seroma, or wound dehiscence were not encountered in this series. The adductor longus flap is a reliable alternative method for inguinal region reconstruction following radical local resection (RLR), radical inguinal lymph node dissection (RILND), or both.
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http://dx.doi.org/10.3389/fsurg.2021.639893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717469PMC
December 2021

Corrigendum to 'dCA1-NAc shell glutamatergic projection mediates context-induced memory recall of morphine' [Pharmacol. Res. 172 (2021) 105857].

Pharmacol Res 2022 Jan 30;175:106044. Epub 2021 Dec 30.

NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2021.106044DOI Listing
January 2022

Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.

Invest Ophthalmol Vis Sci 2021 12;62(15):31

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Purpose: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms.

Methods: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was conducted to analyze the immune cell profiles of CDLNs from normal, EAU, and IL-38-treated mice.

Results: Administration of IL-38 attenuated EAU symptoms and reduced the proportion of T helper 17 (Th17) and T helper 1 (Th1) cells in the retinas and CDLNs. In scRNA-seq analysis, IL-38 downregulated the IL-17 signaling pathway and reduced the expression of Th17 cell pathogenicity-related genes (Csf2 and Il23r), findings which were also confirmed by flow cytometry. In vitro, IL-38 reduced the granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation function of IL-23 and inhibited IL-23R expression in Th17 cells. Moreover, when co-cultured with Th17 cells, IL-38 prevented IL-23 production in antigen-presenting cells (APCs).

Conclusions: Our data demonstrate the therapeutic effect of IL-38 on EAU, and suggest that the effect of IL-38 may be caused by dampening of the GM-CSF/IL-23R/IL-23 feedback loop between Th17 cells and APCs.
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http://dx.doi.org/10.1167/iovs.62.15.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727319PMC
December 2021

Glycolysis Changes the Microenvironment and Therapeutic Response Under the Driver of Gene Mutation in Esophageal Adenocarcinoma.

Front Genet 2021 8;12:743133. Epub 2021 Dec 8.

Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Esophageal cancer is one of the most leading and lethal malignancies. Glycolysis and the tumor microenvironment (TME) are responsible for cancer progressions. We aimed to study the relationships between glycolysis, TME, and therapeutic response in esophageal adenocarcinoma (EAC). We used the ESTIMATE algorithm to divide EAC patients into ESTIMATE and ESTIMATE groups based on the gene expression data downloaded from TCGA. Weighted gene co-expression network analysis (WGCNA) and Gene Set Enrichment Analysis (GSEA) were performed to identify different glycolytic genes in the TME between the two groups. The prognostic gene signature for overall survival (OS) was established through Cox regression analysis. Impacts of glycolytic genes on immune cells were assessed and validated. Next, we conducted the glycolytic gene mutation analysis and drug therapeutic response analysis between the two groups. Finally, the GEO database was employed to validate the impact of glycolysis on TME in patients with EAC. A total of 78 EAC patients with gene expression profiles and clinical information were included for analysis. Functional enrichment results showed that the genes between ESTIMATE and ESTIMATE groups ( = 39, respectively) were strongly related with glycolytic and ATP/ADP metabolic pathways. Patients in the low-risk group had probabilities to survive longer than those in the high-risk group ( < 0.001). Glycolytic genes had significant impacts on the components of immune cells in TME, especially on the T-cells and dendritic cells. In the high-risk group, the most common mutant genes were TP53 and TTN, and the most frequent mutation type was missense mutation. Glycolysis significantly influenced drug sensitivity, and high tumor mutation burden (TMB) was associated with better immunotherapeutic response. GEO results confirmed that glycolysis had significant impacts on immune cell contents in TME. We performed a comprehensive study of glycolysis and TME and demonstrated that glycolysis could influence the microenvironment and drug therapeutic response in EAC. Evaluation of the glycolysis pattern could help identify the individualized therapeutic regime.
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http://dx.doi.org/10.3389/fgene.2021.743133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693172PMC
December 2021

Meta-hologram enabled by a double-face copper-cladded metasurface based on reflection-transmission amplitude coding.

Opt Lett 2022 Jan;47(1):174-177

Here, we propose a double-face copper-cladded meta-hologram that can efficiently manipulate the amplitude of electromagnetic waves in both transmission and reflection spaces, depending on the polarization state of the incident electromagnetic wave. The proposed meta-hologram is validated by encoding the transmission-reflection amplitude information of two independent images into a single metasurface. The holographic images obtained from measurements agree qualitatively with simulation results. The proposed metasurface presents a novel, to the best of our knowledge, scheme for electromagnetic wavefront control in the whole space and overcomes the limitations of narrow frequency band operation.
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http://dx.doi.org/10.1364/OL.442464DOI Listing
January 2022

High GNG4 expression is associated with poor prognosis in patients with lung adenocarcinoma.

Thorac Cancer 2021 Dec 23. Epub 2021 Dec 23.

Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Background: The purpose of this study was to explore the reason for guanine nucleotide binding-protein gamma subunit-4 (GNG4) overexpression and the relationship between GNG4 overexpression and the poor prognosis of lung adenocarcinoma (LUAD) patients.

Methods: The genes and phenotypes related to GNG4 expression in patients with lung adenocarcinoma were analyzed by bioinformatics. The phenotype indicated by bioinformatic analysis was confirmed by experiments.

Results: GNG4 expression is elevated in lung adenocarcinoma, and overexpressed GNG4 is related to the poor prognosis of patients with lung adenocarcinoma. The hypoxic microenvironment of lung adenocarcinoma can promote GNG4 expression and GNG4 promotes the migration and proliferation of lung adenocarcinoma cells.

Conclusions: GNG4 expression in lung adenocarcinoma was significantly higher than in paired adjacent tissues. GNG4 overexpression is associated with a variety of malignant phenotypes of lung adenocarcinoma. Increased GNG4 expression is related to the hypoxic microenvironment in lung adenocarcinoma.
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http://dx.doi.org/10.1111/1759-7714.14265DOI Listing
December 2021

ECAP is a key negative regulator mediating different pathways to modulate salt stress-induced anthocyanin biosynthesis in Arabidopsis.

New Phytol 2021 Dec 23. Epub 2021 Dec 23.

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.

Anthocyanins are a subgroup of plant flavonoids with antioxidant activities and are often induced by various biotic and abiotic stresses in plants, probably to efficiently scavenge free radicals and reactive oxygen species. However, the regulatory mechanisms of salt stress-induced anthocyanin biosynthesis remain unclear. Using molecular and genetic techniques we demonstrated key roles of ECAP in differential salt-responsive anthocyanin biosynthesis pathways in Arabidopsis thaliana. ECAP, JAZ6/8 and TPR2 are known to form a transcriptional repressor complex, and negatively regulate jasmonate (JA)-responsive anthocyanin accumulation. In this study, we demonstrated that under moderate salt stress, the accumulation of anthocyanins is partially dependent on JA signaling, which degrades JAZ proteins but not ECAP. More interestingly, we found that high salinity rather than moderate salinity induces the degradation of ECAP through the 26S proteasome pathway, and this process is independent of JA signaling. Further analysis revealed that ECAP interacts with MYB75 (a transcription factor activating anthocyanin biosynthetic genes) and represses its transcriptional activity in the absence of high salinity. Our results indicated that plants adopt different strategies for fine-tuning anthocyanin accumulation under different levels of salt stress, and further elucidated the complex regulation of anthocyanin biosynthesis during plant development and responses to environmental stresses.
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http://dx.doi.org/10.1111/nph.17937DOI Listing
December 2021

Flexible Multiview Spectral Clustering With Self-Adaptation.

IEEE Trans Cybern 2021 Dec 15;PP. Epub 2021 Dec 15.

Multiview spectral clustering (MVSC) has achieved state-of-the-art clustering performance on multiview data. Most existing approaches first simply concatenate multiview features or combine multiple view-specific graphs to construct a unified fusion graph and then perform spectral embedding and cluster label discretization with k-means to obtain the final clustering results. They suffer from an important drawback: all views are treated as fixed when fusing multiple graphs and equal when handling the out-of-sample extension. They cannot adaptively differentiate the discriminative capabilities of multiview features. To alleviate these problems, we propose a flexible MVSC with self-adaptation (FMSCS) method in this article. A self-adaptive learning scheme is designed for structured graph construction, multiview graph fusion, and out-of-sample extension. Specifically, we learn a fusion graph with a desirable clustering structure by adaptively exploiting the complementarity of different view features under the guidance of a proper rank constraint. Meanwhile, we flexibly learn multiple projection matrices to handle the out-of-sample extension by adaptively adjusting the view combination weights according to the specific contents of unseen data. Finally, we derive an alternate optimization strategy that guarantees desirable convergence to iteratively solve the formulated unified learning model. Extensive experiments demonstrate the superiority of our proposed method compared with state-of-the-art MVSC approaches. For the purpose of reproducibility, we provide the code and testing datasets at https://github.com/shidan0122/FMICS.
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http://dx.doi.org/10.1109/TCYB.2021.3131749DOI Listing
December 2021

A novel hyperspectral compressive sensing framework of plant leaves based on multiple arbitrary-shape regions of interest.

PeerJ Comput Sci 2021 25;7:e802. Epub 2021 Nov 25.

College of Automation, Hangzhou Dianzi University, Hangzhou, Zhejiang Province, China.

Massive plant hyperspectral images (HSIs) result in huge storage space and put a heavy burden for the traditional data acquisition and compression technology. For plant leaf HSIs, useful plant information is located in multiple arbitrary-shape regions of interest (MAROIs), while the background usually does not contain useful information, which wastes a lot of storage resources. In this paper, a novel hyperspectral compressive sensing framework for plant leaves with MAROIs (HCSMAROI) is proposed to alleviate these problems. HCSMAROI only compresses and reconstructs MAROIs by discarding the background to achieve good reconstructed performance. But for different plant leaf HSIs, HCSMAROI has the potential to be applied in other HSIs. Firstly, spatial spectral decorrelation criterion (SSDC) is used to obtain the optimal band of plant leaf HSIs; Secondly, different leaf regions and background are distinguished by the mask image of the optimal band; Finally, in order to improve the compression efficiency, after discarding the background region the compressed sensing technology based on blocking and expansion is used to compress and reconstruct the MAROIs of plant leaves one by one. Experimental results of soybean leaves and tea leaves show that HCSMAROI can achieve 3.08 and 5.05 dB higher PSNR than those of blocking compressive sensing (BCS) at the sampling rate of 5%, respectively. The reconstructed spectra of HCSMAROI are especially closer to the original ones than that of BCS. Therefore, HCSMAROI can achieve significantly higher reconstructed performance than that of BCS. Moreover, HCSMAROI can provide a flexible way to compress and reconstruct different MAROIs with different sampling rates, while achieving good reconstruction performance in the spatial and spectral domains.
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http://dx.doi.org/10.7717/peerj-cs.802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641574PMC
November 2021

Association of Versican Gene Polymorphisms with Intracranial Aneurysm Susceptibility in the Eastern Chinese Population.

Neuropsychiatr Dis Treat 2021 7;17:3531-3537. Epub 2021 Dec 7.

Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People's Hospital of Huainan, Huainan, 232007, People's Republic of China.

Objective: The proteoglycan versican (VCAN) plays an important role in extracellular matrix (ECM) assembly, and diminished maintenance of the ECM has been increasingly regarded as an important factor in the development of intracranial aneurysms (IAs). Previous studies have revealed that single-nucleotide polymorphisms (SNPs) of the VCAN gene are associated with susceptibility to IAs in European or Japanese populations. However, the association between IA susceptibility and VCAN SNPs in the Eastern Chinese population remains unclear. This study aimed to investigate the associations of the SNPs rs251124, rs2287926, and rs173686 with IA susceptibility in the Eastern Chinese population.

Methods: A total of 162 patients with IA and 182 controls were enrolled in this study. The study was conducted between January 2017 and December 2020. SNP genotyping for rs251124, rs2287926, and rs173686 was performed using Kompetitive Allele Specific PCR (KASP) after DNA extraction. The SNP data were analysed with CFX Manager Software version 3.1 (Bio-Rad).

Results: rs251124 and rs173686 were significantly associated with susceptibility to IA. The frequency of rs251124-TT in IA was higher than in controls (OR =1.26, 95% CI: 1.07-1.49; P<0.01), and its risk mainly came from the T allele. Furthermore, logistic regression analysis showed that the T/T genotype and T allele of rs251124 were independent risk factors for IA (OR=1.726, 95% CI: 1.136-2.263; P=0.011). Moreover, the G/G genotype and G allele of rs173686 were associated with increased IA susceptibility (OR=2.52, 95% CI: 1.261-5.037; P=0.009).

Conclusion: The SNPs rs251124 and rs173686 were strongly associated with genetic susceptibility to IA in the Eastern Chinese population; however, no such association was found in the SNP rs2287926 of VCAN. Our findings suggest that the VCAN gene is an IA susceptible gene that should be further studied as a screening marker for IAs.
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http://dx.doi.org/10.2147/NDT.S338311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665873PMC
December 2021

Distinct architecture and composition of mouse axonemal radial spoke head revealed by cryo-EM.

Proc Natl Acad Sci U S A 2021 01;118(4)

State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China;

The radial spoke (RS) heads of motile cilia and flagella contact projections of the central pair (CP) apparatus to coordinate motility, but the morphology is distinct for protozoa and metazoa. Here we show the murine RS head is compositionally distinct from that of Our reconstituted murine RS head core complex consists of Rsph1, Rsph3b, Rsph4a, and Rsph9, lacking Rsph6a and Rsph10b, whose orthologs exist in the protozoan RS head. We resolve its cryo-electron microscopy (cryo-EM) structure at 3.2-Å resolution. Our atomic model further reveals a twofold symmetric brake pad-shaped structure, in which Rsph4a and Rsph9 form a compact body extended laterally with two long arms of twisted Rsph1 β-sheets and potentially connected dorsally via Rsph3b to the RS stalk. Furthermore, our modeling suggests that the core complex contacts the periodic CP projections either rigidly through its tooth-shaped Rsph4a regions or elastically through both arms for optimized RS-CP interactions and mechanosignal transduction.
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http://dx.doi.org/10.1073/pnas.2021180118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848523PMC
January 2021

Ectopic Expression of Induces Stenospermocarpy and Sugar Accumulation in Tomato Fruits.

Front Plant Sci 2021 17;12:759047. Epub 2021 Nov 17.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Seedless fruits are favorable in the market because of their ease of manipulation. Sucrose transporters (SUTs or SUCs) are essential for carbohydrate metabolism in plants. Whether SUTs participate directly in causing stenospermocarpy, thereby increasing fruit quality, remains unclear. Three , namely, , , and from , were characterized and ectopic expression in tomatoes. - and -overexpressing lines had similar flower and fruit phenotypes compared with those of the wild type. -overexpressing lines produced longer petals and pistils, an abnormal stigma, much less and shrunken pollen, and firmer seedless fruits. Moreover, produced fruits from all -overexpressing lines had a higher soluble solid content and sugar concentration. Transcriptomic analysis revealed more genes associated with carbohydrate metabolism and sugar transport and showed downregulation of auxin- and ethylene-related signaling pathways during early fruit development in -overexpressing lines relative to that of the wild type. Our findings demonstrated that stenospermocarpy can be induced by overexpression of through a consequential reduction in nutrient delivery to pollen at anthesis, with a subsequent downregulation of the genes involved in carbohydrate metabolism and hormone signaling. These commercially desirable results provide a new strategy for bioengineering stenospermocarpy in tomatoes and in other fruit plants.
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http://dx.doi.org/10.3389/fpls.2021.759047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637806PMC
November 2021

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas.

Front Immunol 2021 16;12:748820. Epub 2021 Nov 16.

Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in and frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the - neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.
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http://dx.doi.org/10.3389/fimmu.2021.748820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635231PMC
January 2022

The parasitophorous vacuole nutrient channel is critical for drug access in malaria parasites and modulates the artemisinin resistance fitness cost.

Cell Host Microbe 2021 12 3;29(12):1774-1787.e9. Epub 2021 Dec 3.

Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany. Electronic address:

Intraerythrocytic malaria parasites proliferate bounded by a parasitophorous vacuolar membrane (PVM). The PVM contains nutrient permeable channels (NPCs) conductive to small molecules, but their relevance for parasite growth for individual metabolites is largely untested. Here we show that growth-relevant levels of major carbon and energy sources pass through the NPCs. Moreover, we find that NPCs are a gate for several antimalarial drugs, highlighting their permeability properties as a critical factor for drug design. Looking into NPC-dependent amino acid transport, we find that amino acid shortage is a reason for the fitness cost in artemisinin-resistant (ART) parasites and provide evidence that NPC upregulation to increase amino acids acquisition is a mechanism of ART parasites in vitro and in human infections to compensate this fitness cost. Hence, the NPCs are important for nutrient and drug access and reveal amino acid deprivation as a critical constraint in ART parasites.
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http://dx.doi.org/10.1016/j.chom.2021.11.002DOI Listing
December 2021

One-step fabrication of novel MIL-53(Fe, Al) for synergistic adsorption-photocatalytic degradation of tetracycline.

Chemosphere 2021 Nov 26:133032. Epub 2021 Nov 26.

School of Urban Construction, Wuhan University of Science and Technology, Wuhan, 430065, PR China. Electronic address:

Bimetallic MOFs (MIL-53 (Fe, Al)) were successfully fabricated via a facile one-step solvothermal method for the removal of tetracycline (TC) from aqueous solutions. Tetracycline adsorption and photocatalytic experiments indicate that the optimum bimetallic synthetic molar ratio is 3:2 (40%MIL-53(Fe, Al)). The adsorption data are well fitted by the Freundlich model and pseudo-second-order adsorption kinetics. 40%MIL-53(Fe, Al) has an adsorption capacity of up to 402.033 mg/g. After the dark adsorption phase, 10 mg of 40%MIL-53(Fe, Al) can remove 94.33% of the tetracycline in a 70 mL aqueous solution (20 mg/L) under 50 min irradiation, while only 71.39% and 81.82% of the tetracycline are removed by MIL-53(Fe) and MIL-53(Al) under the same conditions. In addition, 40%MIL-53(Fe, Al) exhibits a significant adsorption-photocatalytic synergy (under direct irradiation without a dark adsorption phase), in which the pseudo-first-order kinetic constant increases by a factor of 3.11. Quenching experiments and ESR characterization indicate that ·O, ·OH, and h are the main active species in the photocatalytic process. Meanwhile, 40%MIL-53(Fe, Al) demonstrates good stability, with a tetracycline removal rate that still reaches 83.70% after 4 cycles. These results suggest that the prepared 40%MIL-53(Fe, Al) catalyst is a novel adsorption-photocatalytic material that can be used for the efficient treatment of tetracycline.
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http://dx.doi.org/10.1016/j.chemosphere.2021.133032DOI Listing
November 2021
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