Publications by authors named "Yuan Liu"

3,440 Publications

  • Page 1 of 1

A novel umami electrochemical biosensor based on [email protected]/TiC MXene immobilized T1R1-VFT.

Food Chem 2022 Jul 30;397:133838. Epub 2022 Jul 30.

Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

The bioelectronic tongues based on taste receptors have been emerging with human-like taste perception. However, the practical applications of the receptor-based biosensors were restricted by their narrow and low dynamic ranges. Here, a novel immobilization strategy based on [email protected]/TiC MXene was developed to immobilize the umami ligand binding domain (T1R1-VFT), to fabricate an umami biosensor for umami substances detection. Through the synergic effect of [email protected] and TiC MXene, the capacity to load T1R1-VFT was effectively increased, and the response signal was also amplified by approximately 3 times. The proposed biosensor showed an ultrawide dynamic range of 10-10 M, and a high upper limit of detection, which was closer to the human taste threshold and suitable for detecting foods rich in umami substances. Additionally, the biosensor was successfully applied to detect real samples and analyze the synergistic effects of binary umami substances.
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http://dx.doi.org/10.1016/j.foodchem.2022.133838DOI Listing
July 2022

Generation of Human Domain Antibody Fragments as Potential Insecticidal Agents against by Cadherin-Based Screening.

J Agric Food Chem 2022 Aug 9. Epub 2022 Aug 9.

School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa.

New insecticidal genes and approaches for pest control are a hot research area. In the present study, we explored a novel strategy for the generation of insecticidal proteins. The midgut cadherin of () was used as a target to screen materials that have insecticidal activity. After three rounds of panning, the phage-displayed human domain antibody B1F6, which not only binds to the cadherin CR9-CR11 but also significantly inhibits Cry1Ac toxins from binding to CR9-CR11, was obtained from a phage-displayed human domain antibody (DAb) library. To better analyze the relevant activity of B1F6, soluble B1F6 protein was expressed by BL21 (DE3). The cytotoxicity assays demonstrated that soluble B1F6 induced Sf9 cell death when expressing cadherin on the cell membrane. The insect bioassay results showed that soluble B1F6 protein (90 μg/cm) caused 49.5 ± 3.3% larvae mortality. The midgut histological results showed that soluble B1F6 caused damage to the midgut epithelium of larvae. The present study explored a new strategy and provided a basic material for the generation of new insecticidal materials.
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http://dx.doi.org/10.1021/acs.jafc.2c02000DOI Listing
August 2022

Limited diagnostic value of liver stiffness for clinically significant portal hypertension in HBV-related cirrhosis.

Abdom Radiol (NY) 2022 Aug 9. Epub 2022 Aug 9.

Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.

Purpose: Hepatic venous pressure gradient (HVPG) is the gold standard for portal pressure in cirrhosis, but most previous studies focused on the diagnostic value of clinically significant portal hypertension (CSPH) based on the correlation between liver stiffness (LS) and HVPG in hepatitis C virus (HCV) patients and alcoholic liver. Therefore, it is necessary to clarify the diagnostic value of LS for CSPH and the correlation with HVPG in hepatitis B virus (HBV) patients.

Methods: A total of 137 patients from the Fifth Medical Center of PLA General Hospital were divided into HBV group and non-HBV group according to etiology. Correlation analysis and ROC were used to analyze the correlation between LS and HVPG and the diagnostic value of CSPH.

Results: There was a good correlation between LS and HVPG in the total cohort and non-HBV cohort (r = 0.398, P < 0.001; r = 0.575, P < 0.001, respectively). However, the correlation between LS and HVPG was acceptable in the HBV cohort (r = 0.316, P = 0.002). When adjustment for age, MELD score, and INR, the result was still the same. Similar results were observed in the prediction for CSPH. LS showed good diagnostic value for CSPH in the total cohort and non-HBV cohort (AUC = 0.732, AUC = 0.829, respectively). However, it performed poorly in the HBV cohort (AUC = 0.689).

Conclusion: The etiology of HBV might affect the diagnostic performance of LS for predicting CSPH.
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http://dx.doi.org/10.1007/s00261-022-03632-zDOI Listing
August 2022

Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with hearing loss in clinical practice.

Int J Pediatr Otorhinolaryngol 2022 Jul 31;161:111258. Epub 2022 Jul 31.

Medical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China; Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China. Electronic address:

Background: Hearing loss (HL) is a prevalent sensorineural disorder, and is among the most etiologically heterogeneous disorders. With the advent of next-generation sequencing (NGS) technologies, hundreds of candidate genes can be analyzed simultaneously in a cost-effective manner.

Methods: Ninety-four patients from 87 families diagnosed with non-syndromic or syndromic HL were enrolled. A custom-designed HL panel and clinical exome sequencing (CES) were applied to explore molecular etiology in the cohort, and the efficacy of the two panels was examined.

Results: The etiologic diagnosis for HL has been identified for 36 out of 87 probands (41.4%), 28 with an autosomal recessive (AR) inheritance pattern and 8 with an autosomal dominant (AD) pattern. Candidate variants in 18 different genes were identified in the study cohort, 10 with AR inheritance pattern and 8 with AD pattern. Fourteen of the variants identified in the study were novel.

Conclusions: The custom-designed HL panel covers almost all known HL-associated genes, and can be used as an effective clinical diagnostic platform; CES evaluates all exons related to clinical symptoms, and is also suitable for clinical diagnosis of HL. Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice.
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http://dx.doi.org/10.1016/j.ijporl.2022.111258DOI Listing
July 2022

Controllable Piezo-flexoelectric Effect in Ferroelectric BaSrTiO Materials for Harvesting Vibration Energy.

ACS Appl Mater Interfaces 2022 Aug 8. Epub 2022 Aug 8.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, P. R. China.

The rapid development of the automotive and aerospace industries has led to an increasingly urgent need for electromechanical coupling materials and devices. Here, we have demonstrated the tunable piezo-flexoelectric effect in ferroelectric BaSrTiO materials for scavenging vibration energy. The positive peak output current of an ITO/BaSrTiO/Ag cantilever device based on the flexoelectric effect is only 45 nA at room temperature, which is promoted to 90 nA by the piezo-flexoelectric effect. In addition, the piezo-flexoelectric current of the device can be further boosted to 270 nA by increasing the working temperature to 41.0 °C with a corresponding enhancement ratio of 348.28%. The significantly improved piezo-flexoelectric current is ascribed to the ultrahigh dielectric constant, which is related to the tetragonal-cubic phase transition of the BaSrTiO materials. This work reveals the temperature-modulated piezo-flexoelectric effect in ferroelectric BaSrTiO materials, providing a convenient route for scavenging and sensing of vibration energy.
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http://dx.doi.org/10.1021/acsami.2c09767DOI Listing
August 2022

Corrigendum: Biomarking and induction of apoptosis in ovarian cancer using bifunctional polyethyleneimine-caged platinum nanoclusters.

Front Oncol 2022 20;12:983959. Epub 2022 Jul 20.

Department of Light Chemical Engineering, School of Textiles, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fonc.2022.898917.].
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http://dx.doi.org/10.3389/fonc.2022.983959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346211PMC
July 2022

Angiotensin 1-7 and its analogue decrease blood pressure but aggravate renal damage in preeclamptic mice.

Exp Anim 2022 Aug 8. Epub 2022 Aug 8.

Department of Nephrology, Shanghai Fifth People's Hospital, Fudan University.

Preeclampsia (PE) is a multisystem disease that affects the health of both the pregnant women and the fetus during pregnancy. Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) play a significant role in the pathogenesis of PE. This study aimed to determine the effects of Angiotensin 1-7 (Ang 1-7) and its analogue AVE0991 on AT1-AA-induced PE model. Pregnant mice were divided into five groups: the normal pregnant group, AT1-AA-induced preeclampsia group, and AT1-AA-induced preeclampsia group treated with Losartan, Ang 1-7, and AVE0991, respectively. AT1-AA-induced PE model was established on gestational day 13 by tail intravenous injection of purified AT1-AA polyclonal antibody from serum of guinea pigs. Blood urea nitrogen (BUN), urine albumin and urinary creatinine were measured on day 18 of pregnancy. The systolic blood pressure (SBP) was measured from gestational day 13 to day 18. Renal structure changes were observed via light and electron microscopy. Compared with the normal pregnant group (NP group), AT1-AA-induced preeclampsia group (PE group) exhibited elevated blood pressure and proteinuria, consistent with the characteristics of PE. Ang 1-7 or AVE0991 treatment decreased blood pressure without showing renoprotective effects. The findings indicated that Ang 1-7 and its analogue reduced blood pressure but aggravated renal damage in AT1-AA-induced PE mice.
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http://dx.doi.org/10.1538/expanim.22-0029DOI Listing
August 2022

Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression.

Apoptosis 2022 Aug 5. Epub 2022 Aug 5.

Department of Immunology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Liver ischemia reperfusion injury (IRI) is a serious complication of certain liver surgeries, and it is difficult to prevent. As a potential drug-free treatment, mild hypothermia has been shown to promote positive outcomes in patients with IRI. However, the protective mechanism remains unclear. We established in vivo and in vitro models of hepatic ischemia reperfusion (IR) and mild hypothermia pretreatment. Hepatocytes were transfected with RNA-binding motif protein 3 (RBM3) overexpression plasmids, and IR was performed. Cell, culture medium, blood and tissue samples were collected to assess hepatic injury, oxidative stress, apoptosis and changes in RBM3 expression in the liver. Upregulation of RBM3 expression by mild hypothermia reduced the aminotransferase release, liver tissue injury and mitochondrial injury induced by liver IR. Hepatic IR-induced p38 and c-Jun N-terminal kinase (JNK) signaling pathway activation, oxidative stress injury and apoptosis could be greatly reversed by mild hypothermia. Overexpression of RBM3 mimicked the hepatoprotective effect of mild hypothermia. Mild hypothermia protects the liver from ischemia reperfusion-induced p38 and JNK signaling pathway activation, oxidative stress injury and apoptosis through the upregulation of RBM3 expression.
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http://dx.doi.org/10.1007/s10495-022-01757-6DOI Listing
August 2022

Efficacy of the intraoperative opioid-sparing anesthesia on quality of patients' recovery in video-assisted thoracoscopic surgery: a randomized trial.

J Thorac Dis 2022 Jul;14(7):2544-2555

Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: We aimed to explore the impact of opioid-sparing anesthesia on patients' quality of recovery after video-assisted thoracoscopic surgery (VATS). We tested the primary hypothesis that our predefined opioid-sparing anesthesia provides better quality of patients' recovery compared to routine anesthesia in VATS.

Methods: Patients between 18 and 70 years, scheduled for elective VATS, had an American Society of Anesthesiologists (ASA) class I-III under general anesthesia, were randomly allocated to: routine anesthesia group and opioid-sparing anesthesia group. Patients in the opioid-sparing anesthesia group were mainly given preoperative thoracic paravertebral blockade with intraoperative withholding longer acting opioids. Patients in routine anesthesia group received opioid-based anesthesia. The primary outcome was the Quality of Recovery-15 scale (QoR-15) at 6 hours after surgery. The secondary outcomes included QoR-15 at 24 and 48 hours after surgery, Overall Benefit of Analgesia Score Satisfaction with pain treatment (OBAS) and acute pain intensity at 6, 24 and 48 hours after surgery, and clinical outcomes of recovery after surgery.

Results: A total of 159 patients were included in final analysis. The median difference in QoR-15 between opioid-sparing anesthesia and routine anesthesia was 4 (95% CI: 1-6) at 6 hours, 8 (95% CI: 4-12) at 24 hours and 4.7 (95% CI: 1-6) at 48 hours after surgery respectively; 73.4% of patient showed good recovery in opioid-sparing anesthesia group, compared to 53.8% in routine anesthesia group at 24 hours after surgery (P=0.01). Patients demonstrated lower OBAS in opioid-sparing anesthesia group compared to routine anesthesia at all time points after surgery (P<0.05). The pain at most was significantly lower in opioid-sparing anesthesia group compared to routine anesthesia at 6 and 48 hours after surgery (P<0.05). Patients exhibited faster recovery with opioid-sparing anesthesia on time to mobilize and time to first flatus (P<0.01).

Conclusions: Our intraoperative opioid-sparing anesthesia cannot improve patients' recovery at 6 hours after VATS lung surgery, but it demonstrates better outcomes at 24 hours after surgery compared to routine anesthesia, reaching to a clinically important difference.

Trial Registration: This study is registered in the Chinese Clinical Trial Registry, ChiCTR2000031609.
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http://dx.doi.org/10.21037/jtd-22-50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344409PMC
July 2022

Study on the predictive ability of emergency CHADS score and CHADS-VASc score for coronary artery disease and prognosis in patients with acute ST-segment elevation myocardial infarction.

J Thorac Dis 2022 Jul;14(7):2611-2620

Department of Outpatient, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

Background: Acute ST-segment elevation myocardial infarction (STEMI) has a high morbidity and mortality rate. The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (2 points) (CHADS) and CHADS score with 2 points assigned for age >75 years-vascular disease (CHADS-VASc) scores are widely used for risk stratification management of non-valvular atrial fibrillation stroke and have high prognostic value in cardiovascular disease. This study aims to investigate the predictive value of the emergency CHADS and CHADS-VASc score on coronary artery lesions and prognosis in patients with acute STEMI.

Methods: A total of 524 patients with STEMI from May 2018 to October 2021 were selected for emergency CHADS and CHADS-VASc. Clinical data and laboratory indicators were collected. Patients were evaluated for coronary artery disease (CAD) and prognosis. Logistic regression and the receiver operating characteristic (ROC) curve were used to analyze the data.

Results: In severe group, CysC levels, CHADS, CHADS-VASc score and the proportion of diabetes, stroke or transient ischemic attack (TIA), congestive heart failure, smoking history, Killip class ≥2 was higher than that in mild and moderate group. In poor prognosis group, levels of serum creatinine (Crea), CysC, hemoglobin (Hb), CHADS, CHADS-VASc score and the proportion of hypertension, diabetes, stroke or TIA, congestive heart failure, smoking history, and Killip class ≥2 was higher than that in good prognosis group. Diabetes (OR, 3.678; 95% CI: 2.876-5.872, 0.008), CHADS (OR, 3.829; 95% CI: 2.310-5.832, 0.003) and CHADS-VASc score (OR, 4.671; 95% CI: 3.125-6.187, 0.000) were independent risk factors for the severity of CAD (P<0.05). Diabetes (OR, 3.287; 95% CI: 2.231-5.123, 0.012), Killip class ≥2 (OR, 2.212; 95% CI: 1.023-2.987, 0.045), LVEF (OR, 3.110; 95% CI: 2.124-5.031, 0.023), CHADS (OR, 3.228; 95% CI: 2.133-5.886, 0.005) and CHADS-VASc score (OR, 3.988; 95% CI: 2.987-5.873, 0.001) were independent risk factors for prognosis of acute STEMI patients. Area under curve (AUC) value of CHADS-VASc score in evaluating CAD and prognosis was 0.947, 0.931, higher than that of the CHADS score (0.836, 0.812) (P<0.05).

Conclusions: Multiple factors jointly affect the severity and prognosis of CAD in patients with acute STEMI. The CHADS-VASc score is better than the CHADS score in predicting the severity of coronary artery lesions and prognosis of patients, providing theoretical support for clinical practice.
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http://dx.doi.org/10.21037/jtd-22-763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344425PMC
July 2022

Source Apportionment, Hydrodynamic Influence, and Environmental Stress of Pharmaceuticals in a Microtidal Estuary with Multiple Outlets in South China.

Environ Sci Technol 2022 Aug 3. Epub 2022 Aug 3.

State Key Laboratory of Marine Pollution (SKLMP), City University of Hong Kong, Hong Kong SAR, China.

Pharmaceutical residues in the environment are of great concern as ubiquitous emerging contaminants. This study investigated the presence of 40 pharmaceuticals in water and sediment of the Pearl River Estuary (PRE) in the wet season of 2020. Among psychiatric drugs, only diazepam was found in water samples while six of them were detected in the sediment. The Σantibiotics levels ranged from 6.18 to 35.9 ng/L and 2.63 to 140 ng/g dry weight in water and sediment samples, respectively. Fluoroquinolones and tetracyclines were found well settling in the outlet sediment, while sulfonamides could be released from disturbed sediment under stronger tidal wash-out conditions. After entering the marine waters, pharmaceuticals tended to deposit at the PRE mouth by the influence of the plume bulge and onshore invasion of deep shelf waters. Low ecological risks to the aquatic organisms and of causing antimicrobial resistance were identified. Likewise, hydrological modeling results revealed insignificant risks: erythromycin-HO and sulfamethoxazole discharged through the outlets constituted 30.8% and 6.74% of their environmental capacity, respectively. Source apportionment revealed that pharmaceutical discharges through the Humen and Yamen outlets were predominantly of animal origin. Overall, our findings provide strategic insights on environmental regulations to further minimize the environmental stress of pharmaceuticals in the PRE.
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http://dx.doi.org/10.1021/acs.est.2c02384DOI Listing
August 2022

Chromium in Chinese coals: geochemistry and environmental impacts associated with coal-fired power plants.

Environ Geochem Health 2022 Aug 2. Epub 2022 Aug 2.

State Key Laboratory of Coal Combustion, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.

Chromium (Cr), one of the prime hazardous trace elements in coals, may engender adverse effects on eco-environment and threaten human health during utilization of coal. Based on the samples obtained in our laboratory and published literature, the abundance and modes of occurrence of Cr in Chinese coals, and the environmental impacts associated with coal-fired power plants (CFPPs) were elucidated in this study. With a total of 1397 sets of data, the mean concentration of Cr in Chinese coals was calculated as 21.33 μg/g by the "reserve-concentration" weighted calculation method. Spatially, the average Cr contents increased gradually from North China to South China. Temporally, coals from T, E-N and P were relatively enriched in Cr compared to the other geological time. The Cr concentration in coal varied with different coal ranks. The geological factors accounted for Cr enrichment in coals could be divided into the primary, secondary and epigenetic processes. Higher percentages of organically Cr occurred in low-rank coals, while inorganically associated Cr was mainly found in clay minerals. After coal combustion, most of Cr was enriched in solid wastes (e.g., fly ash and bottom ash). The leaching of Cr from solid wastes in the rainy season (especially acid rain) needs to be a concern for CFPPs. It was estimated that the atmospheric emission of Cr from CFPPs increased annually from 2015 to 2019 and reached approximately 159 tons in 2019.
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http://dx.doi.org/10.1007/s10653-022-01337-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345389PMC
August 2022

Altered temporal-parietal morphological similarity networks in non-small cell lung cancer patients following chemotherapy: an MRI preliminary study.

Brain Imaging Behav 2022 Aug 2. Epub 2022 Aug 2.

Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases, and chemotherapy-related brain changes (known as "chemobrain") in NSCLC patients were found in previous studies. However, the effects of platinum-based chemotherapy on brain structural networks are still unclear. Structural magnetic resonance imaging (sMRI) data were collected from 32 NSCLC patients following platinum-based chemotherapy, 36 NSCLC patients without chemotherapy, and 39 healthy controls. Clinical physiological indicators of patients were collected. Then, morphological similarity networks were constructed using MRI data, and topological properties were calculated using graph theory method. Differences between three groups were investigated using one-way ANOVA and two-sample t-test, and relations between topological properties and clinical physiological indicators were calculated. We found that degree and nodal efficiency in temporal-parietal networks were significantly reduced in NSCLC patients following platinum-based chemotherapy compared to healthy controls/patients without chemotherapy (F-test, p < 0.001; post hoc t-test, p < 0.01, Bonferroni corrected). These changes (p < 0.05) were positively correlated with clinical measures, including thrombocytes, granulocytes and hemoglobin, and were negatively correlated with measures of triglycerides and cholesterol levels. Network properties including clustering coefficient (F(2,104) = 41.435, p < 0.001), number of K-edges (F(2,104) = 40.304, p < 0.001), density of K-edges (F(2,104) = 40.304, p < 0.001), global efficiency (F(2,104) = 42.585, p < 0.001) and small-world (F(2,104) = 37.132, p < 0.001) were also significantly reduced (post hoc t-test, p < 0.01, Bonferroni corrected). These results indicate that platinum-based chemotherapy might cause cerebrovascular damage and clinical indicators' changes, which then cause the properties of morphological similarity networks' changes in the temporal and parietal lobes. This study may help us better understand the "chemobrain" in NSCLC patients.
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http://dx.doi.org/10.1007/s11682-022-00709-7DOI Listing
August 2022

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study.

Lancet Reg Health West Pac 2022 Sep 26;26:100520. Epub 2022 Jul 26.

Shanghai Municipal Center for Disease Control and Prevention, No. 1380 Zhongshan West Street, Changning District, Shanghai City 200051, China.

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China.

Methods: In 2020-2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death).

Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions.

Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms.

Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].
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http://dx.doi.org/10.1016/j.lanwpc.2022.100520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335373PMC
September 2022

ROS-stimulated Protein Lysine Acetylation Is Required for Crown Root Development in Rice.

J Adv Res 2022 Jul 28. Epub 2022 Jul 28.

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, 430070 Wuhan, China. Electronic address:

Introduction: As signal molecules in aerobic organisms, locally accumulated ROS have been reported to balance cell division and differentiation in the root meristem. Protein posttranslational modifications such as lysine acetylation play critical roles in controlling a variety of cellular processes. However, the mechanism by which ROS regulate root development is unknown. In addition, how protein lysine acetylation is regulated and whether cellular ROS levels affect protein lysine acetylation remain unclear.

Objectives: We aimed to elucidate the relationship between ROS and protein acetylation by exploring a rice mutant plant that displays a decreased level of ROS in postembryonic crown root (CR) cells and severe defects in CR development.

Methods: First, proteomic analysis was used to find candidate proteins responsible for the decrease of ROS detected in the wox11 mutant. Then, biochemical, molecular, and genetic analyses were used to study WOX11-regulated genes involved in ROS homeostasis. Finally, acetylproteomic analysis of wild type and wox11 roots treated with or without potassium iodide (KI) and peroxide (HO) were used to study the effects of ROS on protein acetylation in rice CR cells.

Results: We demonstrated that WOX11 was required to maintain ROS homeostasis by upregulating peroxidase genes in the crown root meristem. Acetylproteomic analysis revealed that WOX11-dependent peroxide (HO) levels in CR cells promoted lysine acetylation of many non-histone proteins enriched for nitrogen metabolism and peptide/protein synthesis pathways. Further analysis revealed that the redox state affected histone deacetylases (HDACs) activity, which was likely related to the high levels of protein lysine acetylation in CR cells.

Conclusion: WOX11-controlled ROS level in CR meristem cells is required for protein lysine acetylation which represents a mechanism of ROS-promoted CR development in rice.
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http://dx.doi.org/10.1016/j.jare.2022.07.010DOI Listing
July 2022

Blade needle therapy versus conventional acupuncture for knee osteoarthritis: A meta-analysis.

Medicine (Baltimore) 2022 Jul 29;101(30):e29647. Epub 2022 Jul 29.

Guangxi University of Chinese Medicine, Nanning, China.

Background: This study investigated the hypothesis that the efficacy of blade needle therapy for the treatment of knee osteoarthritis (KOA) is superior to that of conventional acupuncture. In addition, the efficacy of blade needle therapy versus conventional acupuncture for the treatment of KOA was analyzed in a meta-analysis.

Methods: Randomized controlled trials (RCTs) of blade needle therapy and conventional acupuncture for treating KOA were retrieved from the electronic databases CNKL, Wanfang, VIP, PubMed, EMBASE and the Cochrane Library from the commencement of each database to July of 2021. Data were extracted and evaluated by 2 reviewers independently. RevMan 5.3 software was used to conduct the meta-analysis after the studies were evaluated.

Results: A total of 11 RCTs were included, all from China, involving 1142 patients. The meta-analysis results showed that the effective rate of the blade needle group was better than that of the conventional acupuncture group (OR = 3.61, 95% CI [2.56-5.10], P < .00001).

Conclusion: The efficacy of blade needle treatment for KOA is superior to that of conventional acupuncture, but more high-quality studies are needed for future validation due to the low proportion of high-quality studies included and the possible bias factor.
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http://dx.doi.org/10.1097/MD.0000000000029647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333476PMC
July 2022

Impact of Lymph Node Dissection on Survival and Tumor Recurrence for Patients with Resected cT1-2N0 Small Cell Lung Cancer.

Ann Surg Oncol 2022 Jul 29. Epub 2022 Jul 29.

Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: The role of lymph node (LN) dissection for early-stage small cell lung cancer (SCLC) remains unclear. Therefore, this study aimed to investigate the impact of LN dissection on patient survival and tumor recurrence for patients with cT1-2N0M0 SCLC.

Methods: Patients with cT1-2N0M0 SCLC who underwent intent-to-cure surgery at our institution between 2011 and 2019 were retrospectively reviewed. The survival outcomes of patients with systematic LN dissection (n = 112) and LN sampling (n = 35) were compared before and after propensity score-matching (PSM), as were the outcomes for patients with (pN+) and without (pN0) pathologic nodal metastasis. The prognostic impact of LN dissection was evaluated through multivariable analysis.

Results: The dissection group displayed significantly better overall survival (66.4% vs. 48.4%; P = 0.009) and recurrence-free survival (RFS) (63.5% vs. 37.6%;, P = 0.003) than the sampling group at 5 years. The rate of local recurrence was significantly lower in the dissection group than in the sampling group (11.6% vs. 42.9%; P < 0.001). After adjustment by multivariable analysis and PSM, LN dissection retained its independent favorable effects. The overall nodal upstaging rate was 37.6%, and the dissection group had a tendency of better RFS in both the pN0 (P = 0.05) and pN+ (P = 0.036) patients.

Conclusion: Systematic LN dissection is associated with improved survival of patients who undergo surgery for cT1-2N0 SCLC. Further studies are warranted to verify the necessity of LN dissection in the surgery for SCLC.
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http://dx.doi.org/10.1245/s10434-022-12215-7DOI Listing
July 2022

Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis.

Rheumatology (Oxford) 2022 Jul 29. Epub 2022 Jul 29.

Department of Rheumatology and Immunology, Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China.

Objective: To evaluate the use of Janus kinase inhibitor (JAKi) in treating JDM and develop cytokine biomarkers of active disease.

Methods: This study involved a retrospective cohort study that evaluated JAKi in 101 JDM patients as well as a cross-sectional study of cytokines in 128 JDM patients and 30 controls between November 2017 and December 2021 in the Affiliated Children's Hospital of Capital Institute of Pediatrics (China).

Results: During the median follow-up period of 19 months, 65.5% of the patients improved rashes, and CAT-BM scores decreased. 39.6% of JDM patients eliminated glucocorticoids. Muscle strength was improved in all patients who had abnormal muscle strength before JAKi use. Patients and parents provided positive subjective reviews of JAKi, and no serious adverse events were reported. Potential side effects of JAKi included abnormal leukopenia (14/95) and cough (16/83), which affected over 10% of the JDM patients. In the cytokine analysis, 12/34 cytokines were significantly elevated in active JDM patients. Compared with active JDM patients with multiple phenotypes, active JDM patients with only rashes demonstrated lower cytokine levels. Anti-NXP2-positive active patients had lower cytokine levels compared with those without positive anti-NXP2 antibodies. Among all increased cytokines, IL-1RA changed most dramatically, reaching over 793 times the mean of normal values. We developed a panel composed of 6 cytokines to differentiate active or stable status in our cohort (AUC = 0.8486, P < 0.05).

Conclusion: The preliminary evidence suggested that JAKi is a relatively safe and effective alternative for JDM patients. Cytokine profiles could well reflect the inflammatory status of JDM patients.
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http://dx.doi.org/10.1093/rheumatology/keac399DOI Listing
July 2022

Genome-wide analysis of MYB family genes in and their potential roles in terpenoid biosynthesis.

Plant Direct 2022 Jul 22;6(7):e424. Epub 2022 Jul 22.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China.

Terpenoids are a class of significant bioactive components in the woody vine of . Previous studies have shown that MYB transcription factors play important roles in plant secondary metabolism, growth, and developmental processes. However, the MYB involved in terpenoid biosynthesis in are unknown. To identify MYB (TwMYB) genes that are involved in terpenoid biosynthesis, we conducted the genome-wide analysis of the TwMYB gene family. A total of 207 TwMYBs were identified including 84 1R-TwMYB, 117 R2R3-TwMYB, four 3R-TwMYB, and two 4R-TwMYB genes. The most abundant R2R3-TwMYBs together with their Arabidopsis homologs were categorized into 26 subgroups. Intraspecific collinearity analysis found that the 74.9% of the TwMYBs may be generated by segmental duplication events, and 36.7% of duplicated gene pairs were derived from the specific whole genome duplication (WGD) event in . In addition, interspecies collinearity analysis found that 16 TwMYB genes formed homologous gene pairs with MYB genes in seven representative species, which indicated they may have a key role in evolution. Notably, we found that the TwMYB genes were differentially expressed in various tissues by expression pattern analysis. In order to further select the candidate genes related to terpenoid biosynthesis, the assay of Methyl jasmonate (MeJA) induction and analysis of phylogenetic tree was conducted. It was speculated that six candidate TwMYB genes (, , , , , and ) are involved in regulating terpenoid biosynthesis. This study is the first systematic analysis of the TwMYB gene family and will lay a foundation for the functional characterization of TwMYB genes in the regulation of terpenoid biosynthesis.
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http://dx.doi.org/10.1002/pld3.424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307386PMC
July 2022

Bioassay-based identification and removal of target and suspect toxicants in municipal wastewater: Impacts of chemical properties and transformation.

J Hazard Mater 2022 09 20;437:129426. Epub 2022 Jun 20.

Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 510443, China.

Municipal wastewater contains numerous chemicals and transformation products with highly diverse physiochemical properties and intrinsic toxicity; thus, it is imperative but challenging to identify major toxicants. Herein, toxicity identification evaluation (TIE) was applied to identify major toxicants in a typical municipal wastewater treatment plant (WWTP). Impacts of chemical properties on the removal of contaminants and toxicity at individual treatment stages were also examined. The WWTP influent caused 100% death of Daphnia magna and zebrafish embryos, and toxicity characterization suggested that organics, metals, and volatiles all contributed to the toxicity. Toxicity identification based on 189 target and approximately one-thousand suspect chemicals showed that toxicity contributions of organic contaminants, metals, and ammonia to D. magna were 77%, 4%, and 19%, respectively. Galaxolide, pyrene, phenanthrene, benzo[a]anthracene, fluoranthene, octinoxate, silver, and ammonia were identified as potential toxicants. Comparatively, the detected transformation products elicited lower toxicity than their respective parent contaminants. In contrast, the analyzed contaminants showed negligible contributions to the toxicity of zebrafish embryos. Removal efficiencies of these toxicants in WWTP were highly related to their hydrophobicity. Diverse transformation and removal efficiencies of contaminants in WWTPs may influence the chemical compositions in effluent and ultimately the risk to aquatic organisms in the receiving waterways.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129426DOI Listing
September 2022

Rhamnazin Inhibits Hepatocellular Carcinoma Cell Aggressiveness In Vitro via Glutathione Peroxidase 4-Dependent Ferroptosis.

Tohoku J Exp Med 2022 Jul 28. Epub 2022 Jul 28.

Department of Pharmacy, The First Affiliated Hospital of Soochow University.

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http://dx.doi.org/10.1620/tjem.2022.J061DOI Listing
July 2022

3D porous carbon conductive network with highly dispersed Fe-Nx sites catalysts for oxygen reduction reaction.

Nanotechnology 2022 Jul 27. Epub 2022 Jul 27.

School of Physics and Electronic Engineering, Jiangsu University, #301 Xuefu Road, Zhenjiang, 212013, CHINA.

Intrinsic activity and reactive numbers are considered two important factors in oxygen reduction reaction (ORR) catalysts. Herein, we report the rational design and synthesis of a strongly coupled hybrid material comprising of FeZn nanoparticles (FeZn NPs) supported by a three-dimensional carbon conductive network (FeZn [email protected]) for increased ORR performance. Fe-N-C sites can offer high intrinsic activity owing to the unique bonding and oxygen vacancies, and the carbon conductive network facilitates the exposure active sites, increasing electron transport. Because of the synergetic effect of the conductive networks containing Fe-N-C and polyaniline, the catalysts exhibited ORR activity in an alkaline medium via a four-electron transfer process. FeZn [email protected] exhibited outstanding performance with a limited current density (6.2 mA cm-2), the Tafel slope (81.19 mV dec-1), and stability (23 mV negative shift after 2000 cycles), which were superior to those of 20% Pt/C (5.7 mA cm-2, 75.1 mV dec-1, 36 mV negative shift after 2000 cycles). This research highlights the effect of conductive networks expanding pathways and reducing the resistance of mass transport, which is a facile method to generate superior ORR electrocatalysts.
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http://dx.doi.org/10.1088/1361-6528/ac8487DOI Listing
July 2022

Boryl-Dictated Site-Selective Intermolecular Allylic and Propargylic C-H Amination.

J Am Chem Soc 2022 Aug 27;144(31):14380-14387. Epub 2022 Jul 27.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou510006, China.

For internal alkenes possessing two or more sets of electronically and sterically similar allylic protons, the site-selectivity for allylic C-H functionalization is fundamentally challenging. Previously, the negative inductive effect from an electronegative atom has been demonstrated to be effective for several inspiring regioselective C-H functionalization reactions. Yet, the use of an electropositive atom for a similar purpose remains to be developed. α-Aminoboronic acids and their derivatives have found widespread applications. Their current syntheses rely heavily on functional group manipulations. Herein we report a boryl-directed intermolecular C-H amination of allyl -methyliminodiacetyl boronates (B(MIDA)s) and propargylic B(MIDA)s to give α-amino boronates with an exceptionally high level of site-selectivities (up to 300:1). A wide variety of highly functionalized secondary and tertiary α-amino boronates are formed in generally good to excellent yields, thanks to the mildness of the reaction conditions. The unsaturated double and triple bonds within the product leave room for further decorations. Mechanistic studies reveal that the key stabilization effect of the B(MIDA) moiety on its adjacent developing positive charge is responsible for the high site-selectivity and that a closed transition state might be involved, as the reaction is fully stereoretentive. An activation effect of B(MIDA) is also found.
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http://dx.doi.org/10.1021/jacs.2c06117DOI Listing
August 2022

Electrochemical Signal Amplification Strategies and Their Use in Olfactory and Taste Evaluation.

Biosensors (Basel) 2022 Jul 26;12(8). Epub 2022 Jul 26.

Tianjin Key Laboratory of Food Biotechnology, College of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, China.

Biosensors are powerful analytical tools used to identify and detect target molecules. Electrochemical biosensors, which combine biosensing with electrochemical analysis techniques, are efficient analytical instruments that translate concentration signals into electrical signals, enabling the quantitative and qualitative analysis of target molecules. Electrochemical biosensors have been widely used in various fields of detection and analysis due to their high sensitivity, superior selectivity, quick reaction time, and inexpensive cost. However, the signal changes caused by interactions between a biological probe and a target molecule are very weak and difficult to capture directly by using detection instruments. Therefore, various signal amplification strategies have been proposed and developed to increase the accuracy and sensitivity of detection systems. This review serves as a reference for biosensor and detector research, as it introduces the research progress of electrochemical signal amplification strategies in olfactory and taste evaluation. It also discusses the latest signal amplification strategies currently being employed in electrochemical biosensors for nanomaterial development, enzyme labeling, and nucleic acid amplification techniques, and highlights the most recent work in using cell tissues as biosensitive elements.
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http://dx.doi.org/10.3390/bios12080566DOI Listing
July 2022

ITGβ6 Facilitates Skeletal Muscle Development by Maintaining the Properties and Cytoskeleton Stability of Satellite Cells.

Life (Basel) 2022 Jun 21;12(7). Epub 2022 Jun 21.

Agricultural Technology Innovation Center in Mountainous Areas of Hebei Province, Hebei Agricultural University, Baoding 071000, China.

Integrin proteins are important receptors connecting the intracellular skeleton of satellite cells and the extracellular matrix (ECM), playing an important role in the process of skeletal muscle development. In this research, the function of ITGβ6 in regulating the differentiation of satellite cells was studied. Transcriptome and proteome analysis indicated that is a key node connecting ECM-related proteins to the cytoskeleton, and it is necessary for the integrity of the membrane structure and stability of the cytoskeletal system, which are essential for satellite cell adhesion. Functional analysis revealed that the ITGβ6 protein could affect the myogenic differentiation potential of satellite cells by regulating the expression of PAX7 protein, thus regulating the formation of myotubes. Moreover, ITGβ6 is involved in muscle development by regulating cell-adhesion-related proteins, such as β-laminin, and cytoskeletal proteins such as PXN, DMD, and VCL. In conclusion, the effect of ITGβ6 on satellite cell differentiation mainly occurs before the initiation of differentiation, and it regulates terminal differentiation by affecting satellite cell characteristics, cell adhesion, and the stability of the cytoskeleton system.
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http://dx.doi.org/10.3390/life12070926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318838PMC
June 2022

Modifications of microplastics in urban environmental management systems: A review.

Water Res 2022 Jul 9;222:118843. Epub 2022 Jul 9.

Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, China; Center for Environmental Microplastics Studies, Jinan University, Guangzhou 511443, China. Electronic address:

Microplastics (MPs) are a worldwide environmental pollution issue. Besides the natural environmental stresses, various treatments in urban environmental management systems induce modifications on MPs, further affecting their environmental behavior. Investigating these modifications and inherent mechanisms is crucial for assessing the environmental impact and risk of MPs. In this review, up-to-date knowledge regarding the modifications of MPs in urban environmental management systems was summarized. Variations of morphology, chemical composition, hydrophilicity and specific surface area of MPs were generalized. The aging and degradation of MPs during drinking water treatment, wastewater treatment, sewage sludge treatment and solid waste treatment were investigated. A high abundance of MPs occurred in sewage sludge and aging solid waste, while digestion and composting contributed to significant decomposition and reduction of MPs. These treatments have become converters for MPs before entering the environment. Several novel technologies for MPs removal were listed; However, no appropriate methods can be put into actual application by now, except the membrane separation. The corresponding effects of degradation on the behaviors of MPs, including adsorption, sinking and contaminant leakage, were discussed. Finally, three priorities for research were proposed. This critical review provides viewpoints and references for risk evaluation of MPs after treatments in urban environmental management systems.
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http://dx.doi.org/10.1016/j.watres.2022.118843DOI Listing
July 2022

Association between smoking and COVID-19 severity: A multicentre retrospective observational study.

Medicine (Baltimore) 2022 Jul 22;101(29):e29438. Epub 2022 Jul 22.

Department of Orthopedics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

The relationship between smoking and coronavirus disease 2019 (COVID-19) severity remains unclear. This study aimed to investigate the effect of smoking status (current smoking and a smoking history) on the clinical severity of COVID-19. Data of all enrolled 588 patients, who were referred to 25 hospitals in Jiangsu province between January 10, 2020 and March 14, 2020, were retrospectively reviewed. Univariate and multivariate regression, random forest algorithms, and additive interaction were used to estimate the importance of selective predictor variables in the relationship between smoking and COVID-19 severity. In the univariate analysis, the proportion of patients with a current smoking status in the severe group was significantly higher than that in the non-severe group. In the multivariate analysis, current smoking remained a risk factor for severe COVID-19. Data from the interaction analysis showed a strong interaction between the number of comorbidities in patients with COVID-19 and smoking. However, no significant interaction was found between smoking and specific comorbidities, such as hypertension, diabetes, etc. In the random forest model, smoking history was ranked sixth in mean decrease accuracy. Active smoking may be significantly associated with an enhanced risk of COVID-19 progression towards severe disease. However, additional prospective studies are needed to clarify the complex relationship between smoking and COVID-19 severity.
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http://dx.doi.org/10.1097/MD.0000000000029438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302364PMC
July 2022

Circ_0000520 interacts with miR-512-5p to upregulate KIAA0100 to promote malignant behaviors in lung cancer.

Histol Histopathol 2022 Jul 22:18498. Epub 2022 Jul 22.

Department of Respiratory and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai, China.

Background: CircRNAs function as pivotal molecules to regulate the malignant development of lung cancer. This study was designed to research the functional role and how it acted in lung cancer progression.

Methods: Circ_0000520, microRNA-512-5p (miR-512-5p) and Breast cancer-overexpressed gene 1 (KIAA0100) levels were measured through reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used to examine cell proliferation. Cell cycle and apoptosis were evaluated via flow cytometry. The protein levels were determined using western blot. Cell migration and invasion were assessed by wound healing assay and transwell assay. The circ_0000520 function in vivo was explored by tumor xenograft assay. The molecular interaction was analyzed via Dual-luciferase reporter assay.

Results: Circ_0000520 was obviously upregulated in lung cancer tissues and cells. Silence of circ_0000520 inhibited proliferation, cell cycle progression, migration, invasion and angiogenesis but promoted cell apoptosis. Circ_0000520 downregulation reduced tumor growth of lung cancer in vivo. Circ_0000520 served as a miR-512-5p sponge. The oncogenic function of circ_0000520 was partly achieved by sponging miR-512-5p in lung cancer. KIAA0100 was a target of miR-512-5p and miR-512-5p inhibited the malignant behaviors of lung cancer cells via downregulating KIAA0100. Circ_0000520 targeted miR-512-5p to regulate the level of KIAA0100.

Conclusion: All these data demonstrated that circ_0000520 was able to drive the progression of lung cancer via the mediation of miR-512-5p/KIAA0100 axis. Circ_0000520 might be a potential biomarker for lung cancer.
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http://dx.doi.org/10.14670/HH-18-498DOI Listing
July 2022

A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade.

Clin Lung Cancer 2022 Jun 22. Epub 2022 Jun 22.

Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.

Background: There is an urgent and unmet need for more effective treatment options for patients with metastatic and recurrent non-small-cell lung cancer (NSCLC) who progressed on platinum-based therapy, immune checkpoint inhibitors (ICI), and targeted therapies. Currently, the combination of docetaxel (D) and ramucirumab (R) is the next best salvage therapy with a modest historical progression free survival (PFS) of 4.5 months and 6-month PFS rate of 37% predating the era of ICI use. Anecdotal reports in patients who progressed on ICI suggest a higher response rate to docetaxel compared to historical experience. Furthermore, tumor related angiogenesis promotes tumor growth and may contribute to immune escape in patients treated with ICI. Therapeutic combination with anti-angiogenic, ICI, and chemotherapy have independently demonstrated clinical efficacy without additive toxicities in NSCLC patients.

Patients And Methods: This multicenter, single arm, open label, phase 2 study will evaluate the safety and preliminary efficacy of the combination of docetaxel 75 mg/m, ramucirumab 10 mg/kg, and pembrolizumab 200 mg in up to 41 patients with metastatic or recurrent NSCLC after progression on concomitant or sequential platinum-based chemotherapy and ICI. This treatment will be given intravenously on the same day every 3 weeks until disease progression, occurrence of severe side effects, or no clinical benefit. The primary endpoint is 6-month PFS rate.

Conclusions: This is the first study to evaluate the safety and efficacy of ICI combined with docetaxel and ramucirumab. The findings could provide valuable information for developing new treatment strategies for NSCLC patients.
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http://dx.doi.org/10.1016/j.cllc.2022.06.003DOI Listing
June 2022

Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood.

J Immunother Cancer 2022 Jul;10(7)

Winship Cancer Institute, Emory University, Atlanta, Georgia, USA

Purpose: Checkpoint therapy is now the cornerstone of treatment for patients with renal cell carcinoma (RCC) with advanced disease, but biomarkers are lacking to predict which patients will benefit. This study proposes potential immunological biomarkers that could developed for predicting therapeutic response in patients with RCC.

Methods: Using flow cytometry, RNA sequencing, and T-cell receptor (TCR) sequencing, we investigated changes in T cells in the peripheral blood of patients with advanced RCC after receiving immunotherapy. We used immunofluorescence (IF) imaging and flow cytometry to investigate how intratumoral T cells in patients' tumors (resected months/years prior to receiving checkpoint therapy) predicted patient outcomes after immunotherapy.

Results: We found that a small proportion of CD4 and CD8 T cells in the blood activate following checkpoint therapy, expressing the proliferation marker Ki67 and activation markers HLA-DR and CD38. Patients who had the highest increase in these HLA-DR +CD38+CD8 T cells after treatment had the best antitumor immune response and experienced clinical benefit. Using RNA sequencing, we found that while these cells expanded in most patients, their phenotype did not drastically change during treatment. However, when we analyzed the TCR repertoire of these HLA-DR +CD38+CD8+T cells, we found that only patients who clinically benefitted had a burst of new clonotypes enter this pool of activated cells. Finally, we found that abundant T cells in the untreated tumors predicted clinical benefit to checkpoint therapy on disease progression.

Conclusions: Together, these data suggest that having a strong pre-existing immune response and immediate peripheral T-cell activation after checkpoint therapy is a predictor of clinical benefit in patients with RCC.
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http://dx.doi.org/10.1136/jitc-2022-004803DOI Listing
July 2022
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