Publications by authors named "Jian Li"

6,315 Publications

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Synergistic antibacterial effects of low-intensity ultrasound and peptide LCMHC against Staphylococcus aureus.

Int J Food Microbiol 2022 May 9;373:109713. Epub 2022 May 9.

College of Ocean Food and Biological Engineering, Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Jimei University, 43 Yindou Road, Xiamen, Fujian 361021, China. Electronic address:

The increasing demand for ready-to-eat fresh foods requires the use of non-thermal sterilization, hence, the application of antimicrobial peptides (AMPs) combined with ultrasound could serve as a novel food preservation method to prevent foodborne diseases. In this study, in silico tools were used to predict and screen potential AMPs from the antimicrobial amino acid sequence of myosin heavy chain of Larimichthys crocea. A novel AMP, designated as LCMHC, had strong antibacterial activity against Staphylococcus aureus when combined with low-intensity ultrasound treatment. The minimal inhibitory concentration (MIC) of LCMHC was 125 μg/mL when used alone but 31.25 μg/mL when combined with 0.3 W/cm ultrasound treatment. Structural analysis using circular dichroism (CD) revealed that peptide LCMHC has α-helical structure, which had slightly untwisting effect with increasing ultrasonic intensity. Transmission electron microscopy and permeability analysis of bacteria cell membrane showed that low-intensity ultrasound combined with peptide LCMHC could greatly improve the cell membrane permeability of S. aureus. Moreover, low intensity-ultrasound could assist the entry of more peptide LCMHC into bacterial cells to bind DNA. The findings here provide new insight into the potential application of peptide LCMHC combined with low-intensity ultrasound in the food industry.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2022.109713DOI Listing
May 2022

Titanium scaffold loaded with strontium and copper double-doped hydroxyapatite can inhibit bacterial growth and enhance osteogenesis.

J Biomater Appl 2022 May 20:8853282221080525. Epub 2022 May 20.

600870People's Liberation Army General Hospital of Western Theater Command, Chengdu, China.

Co-doping of multiple ions can effectively adjust the biological properties of hydroxyapatite (HA) for various biomedical applications. In this study, we prepared Sr and Cu double-doped hollow HA and characterized them by SEM, EDS, XRD, FTIR, and other methods. We found that Sr and Cu were uniformly distributed in the hollow carbonic acid HA microspheres. As the proportion of metal elements increases, the microspherical appearance and crystallinity properties also change. In addition, we also prepared porous titanium scaffolds through 3D printing technology and constructed composite scaffolds of porous titanium scaffolds, Sr and Cu double-doped HA, and gelatin. In vitro cell experiments and bacterial experiments, the composite scaffolds, especially the 10%Cu-10%Sr- HA/Gel/Ti group scaffolds, have good biocompatibility and integration with bone tissues, promoting the proliferation and differentiation of BMSCs while having excellent antibacterial properties. These composite scaffolds can simultaneously achieve bone defect filling, osteoblast differentiation, and antibacterial functions, owning broad clinical application prospects.
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http://dx.doi.org/10.1177/08853282221080525DOI Listing
May 2022

A Highly Effective, UV-Curable, Intumescent, Flame-Retardant Coating Containing Phosphorus, Nitrogen, and Sulfur, Based on Thiol-Ene Click Reaction.

Materials (Basel) 2022 May 7;15(9). Epub 2022 May 7.

The Ministry of Education Key Laboratory of Automotive Material, College of Materials Science and Engineering, Jilin University, Changchun 130025, China.

In this paper, a flame-retardant, UV-cured coating was prepared on the fiber composites' (FC) surface via a thiol-ene click reaction using pentaerythritol tetra(3-mercaptopropionate) (PETMP), triallyl cyanurate (TAC), and 2-hydroxyethyl methacrylate phosphate (PM-2). The synergistic effectiveness of phosphorus (P), nitrogen (N), and sulfur (S) was studied in detail by changing the proportion of these reactants. Sample S(NP) with a molar ratio of N and P elements of 3:2, and the thiol and vinyl groups of 4:6 had the highest LOI value (28.6%) and was self-extinguishing in the horizontal combustion test. It had the lowest peak heat release rate (PHRR) value (279.25 kW/m) and total smoke production (2.18 m). Moreover, the thermogravimetric analysis (TG) showed that the decomposition process of the coated composites was delayed. The conversion rate of the double bond and the thiol of S(NP) was 100% and 92.0%, respectively, which showed that the cross-linked network structure was successfully formed. The tensile strength and the flexural strength of coated composites improved, and the transparency of the coating can reach 90%. These characteristics showed that the UV-cured coatings could be used in industrial production to effectively prevent fires.
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http://dx.doi.org/10.3390/ma15093358DOI Listing
May 2022

Analysis of Clinical and Genetic Characterization of Three Ataxia-Telangiectasia Pedigrees With Novel Gene Mutations.

Front Pediatr 2022 2;10:877826. Epub 2022 May 2.

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

Objective: The clinical manifestations of ataxia-telangiectasia (AT) are very complex and are easily misdiagnosed and missed. The purpose of this study was to explore the clinical characteristics and genetic features of five pediatric patients with AT from three pedigrees in china.

Methods: Retrospectively collected and analyzed the clinical data and genetic testing results of five AT patients diagnosed by the Whole-exome sequencing followed by Sanger sequencing. The five patients with AT were from three pedigrees, including two female patients (case 1 and case 2) in pedigree I, one male patient (case 3) in pedigree II, and two male patients (case 4 and case 5) in pedigree III. According to the United Kingdom Association for Clinical Genomic Science Best Practice Guidelines for Variants Classification in Rare Disease 2020 to grade the genetic variants.

Results: Five patients had mainly clinical presentations including unsteady gait, dysarthria, bulbar conjunctive telangiectasia, cerebellar atrophy, intellectual disability, stunted growth, increase of alpha-fetoprotein in serum, lymphopenia. Notably, one patient with classical AT presented dystonia as the first symptom. One patient had recurrent infections, five patients had serum Immunoglobulin (Ig) A deficiency, and two patients had IgG deficiency. In three pedigrees, we observed five pathogenic variants of the gene, which were c.1339C>T (p.Arg447Ter), c.7141_7151delAATGGAAAAAT (p.Asn2381GlufsTer18), c.437_440delTCAA (p.Leu146GlnfsTer6), c.2482A>T (p.Lys828Ter), and c.5495_5496+2delAAGT (p.Glu1832GlyfsTer4). Moreover, the c.437_440delTCAA, c.2482A>T, and c.5495_5496+2delAAGT were previously unreported variants.

Conclusions: Pediatric patients with classical AT may present dystonia as the main manifestation, or even a first symptom, besides typical cerebellar ataxia, bulbar conjunctive telangiectasia, etc. Crucially, we also found three novel pathogenic gene variants (c.437_440delTCAA, c.2482A>T, and c.5495_5496+2delAAGT), expanding the pathogenic gene mutation spectrum.
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http://dx.doi.org/10.3389/fped.2022.877826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108171PMC
May 2022

Giant Negative Magnetoresistance beyond Chiral Anomaly in Topological Material YCuAs.

Adv Mater 2022 May 18:e2201597. Epub 2022 May 18.

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Physics, and Key Laboratory of Strongly-Coupled Quantum Matter Physics, Chinese Academy of Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China.

Large negative magnetoresistance (MR) effect, which usually emerges in various magnetic systems, is a technologically important property for spintronics. Recently, the so-called "chiral anomaly" in topological semimetals offers an alternative to generate considerable negative MR effect without utilizing magnetism. However, it requires that the applied magnetic field must be strictly along the electric current direction, which sets a strong limit for practical applications. Here, we discover a giant negative MR effect with a value of up to -40% in 9 T at 2 K in a nonmagnetic Dirac material YCuAs , which is not restricted to the specific configuration for applied magnetic fields. Based on magnetic susceptibility and nuclear magnetic resonance measurements, the giant negative MR effect is tightly connected with the unexpected spin-dependent scattering from vacancy-induced local moments, which is also beyond classical Kondo effect. The present work not only offers an alternative route for spintronics based on nonmagnetic topological materials, but also helps to further understand the negative MR effect in topological materials. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202201597DOI Listing
May 2022

Indoleamine 2,3-Dioxygenase 1 Deletion-Mediated Kynurenine Insufficiency in Vascular Smooth Muscle Cells Exacerbates Arterial Calcification.

Circulation 2022 May 18:101161CIRCULATIONAHA121057868. Epub 2022 May 18.

Center for Molecular and Translational Medicine, Georgia State University, Atlanta (L.Q., C.J.Y., P.S., J.L., Y.D., M.H.Z.).

Background: IDO1 (indoleamine 2,3-dioxygenase 1) is the rate-limiting enzyme for tryptophan metabolism. IDO1 malfunction is involved in the pathogenesis of atherosclerosis. Vascular smooth muscle cells (VSMCs) with an osteogenic phenotype promote calcification and features of plaque instability. However, it remains unclear whether aberrant IDO1-regulated tryptophan metabolism causes VSMCs osteogenic reprogramming and calcification.

Methods: We generated global apoE (apolipoprotein E) and IDO1 double knockout mice, and apoE knockout mice with specific deletion of IDO1 in VSMCs or macrophages. Arterial intimal calcification was evaluated by a Western diet-induced atherosclerotic calcification model.

Results: Global deficiency of IDO1 boosted calcific lesion formation without sex bias in vivo. Conditional IDO1 loss of function in VSMCs rather than macrophages promoted calcific lesion development and the abundance of RUNX2 (runt-related transcription factor 2). In contrast, administration of kynurenine via intraperitoneal injection markedly delayed the progression of intimal calcification in parallel with decreased RUNX2 expression in both and mice. We found that IDO1 deletion restrained RUNX2 from proteasomal degradation, which resulted in enhanced osteogenic reprogramming of VSMCs. Kynurenine administration downregulated RUNX2 in an aryl hydrocarbon receptor-dependent manner. Kynurenine acted as the endogenous ligand of aryl hydrocarbon receptor, controlled resultant interactions between cullin 4B and aryl hydrocarbon receptor to form an E3 ubiquitin ligase that bound with RUNX2, and subsequently promoted ubiquitin-mediated instability of RUNX2 in VSMCs. Serum samples from patients with coronary artery calcification had impaired IDO1 activity and decreased kynurenine catabolites compared with those without calcification.

Conclusions: Kynurenine, an IDO1-mediated tryptophan metabolism main product, promotes RUNX2 ubiquitination and subsequently leads to its proteasomal degradation via an aryl hydrocarbon receptor-dependent nongenomic pathway. Insufficient kynurenine exerts the deleterious role of IDO1 ablation in promoting RUNX2-mediated VSMCs osteogenic reprogramming and calcification in vivo.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057868DOI Listing
May 2022

Distribution of mature and newly regenerated nerve fibers after tooth extraction and dental implant placement: an immunohistological study.

J Oral Rehabil 2022 May 16. Epub 2022 May 16.

Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, P.R. China.

Background: The time-dependent peri-implant innervation needs to be elucidated in detail.

Objectives: To examine the distribution of mature and newly regenerated nerves around the implant with immunofluorescence during 28-days follow-up after implantation.

Methods: 35 male Sprague-Dawley rats were grouped into non-operated(n=5), extraction(n=5), and implant(n=25) groups. For rats in the extraction and implant groups, three right maxillary molars were extracted. One month later, a titanium implant was placed into the healed alveolar ridge in the implant group. The implant group was further divided into 5 subgroups according to day 1, 3, 7, 14, or 28 after implantation, on which day serial histological sections were prepared for immunohistochemistry. On day 28, the serial sections were also prepared in the non-operated and extraction groups. Soluble protein-100 and growth-associated protein-43 were used to immunolabel mature and newly regenerated nerve fibers respectively.

Results: In the peri-implant soft tissues, the number of both mature and newly regenerated nerves showed an increasing trend in 28 days. In the bone tissues, the number of mature or newly regenerated nerves in both areas at less than 100 μm and 100-200 μm from the implant surface on day 28 grew significantly compared with that on day 1 or 3. In addition, the closest distance from mature nerves to the implant surface decreased evidently.

Conclusion: The number of peri-implant nerves increased in 28 days since implantation. The innervation in the soft tissue took place faster than in the bone tissue. The mature nerves in the bone tissue approached the implant gradually.
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http://dx.doi.org/10.1111/joor.13338DOI Listing
May 2022

Hofmeister Effect Mediated Strong PHEMA-Gelatin Hydrogel Actuator.

ACS Appl Mater Interfaces 2022 May 16. Epub 2022 May 16.

Institute of Materials Research and Engineering, Agency for Science, Technology and Research, 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634, Singapore.

Hydrogels have become popular in biomedical applications, but their applications in muscle and tendon-like bioactuators have been hindered by low toughness and elastic modulus. Recently, a significant toughness enhancement of a single hydrogel network has been successfully achieved by the Hofmeister effect. However, little has been conducted for the Hofmeister effect on the hybrid hydrogels, although they have a special network structure consisting of two types of polymer components. Herein we fabricated hybrid poly(2-hydroxyethyl methacrylate) (PHEMA)-gelatin hydrogels with high mechanical performance and stimuli response. An ideal bicontinuous phase separation structure of the PHEMA (rigid) and gelatin (ductile) was observed with embedded microdisc-like gelatin in the three-dimensional polymeric network of PHEMA. A significant enhancement of mechanical performance by the Hofmeister effect was attributed to the salting-out-induced stronger and closer interphase interaction between PHEMA and gelatin. A superior comprehensive mechanical performance with fracture elongation over 650%, tensile strength of 5.2 MPa, toughness of 13.5 MJ/m, and modulus of 45.6 MPa was achieved with the salting-out effect. More specifically, the synergy of phase separation and Hofmeister effect enable the hydrogel to contract with an enhanced modulus in high-concentration salt solutions, while the same hydrogel swells and relaxes in dilute solutions, exhibiting an ionic stimulus response and excellent shape-memory properties like those of most artificial muscle. This is manifested in highly stretched, twisted, and knotted hydrogel strips that can rapidly recover their original shape in a dilute salt solution. The high strength and modulus, ionic stimuli response, and shape memory property make the hybrid hydrogel a promising material for bioactuators in various biomedical applications.
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http://dx.doi.org/10.1021/acsami.2c01922DOI Listing
May 2022

Relationship between lipoprotein(a) and revascularization after percutaneous coronary intervention in type 2 diabetes mellitus patients with acute coronary syndrome.

Curr Med Res Opin 2022 May 14:1-30. Epub 2022 May 14.

Department of Cardiology, the Affiliated Hospital of Qingdao University, China.

Background: As a residual risk factor for coronary heart disease, lipoprotein(a) [Lp(a)] is associated with the occurrence of cardiovascular events after percutaneous coronary intervention (PCI). The revascularization rate after PCI is high among diabetic patients. However, the relationship between Lp(a) and revascularization after PCI in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) remains unclear.

Methods: The investigation was a single-center, observational, retrospective cohort study. Patients with T2DM who were first diagnosed with ACS and underwent PCI were included in the study. As a result, 362 patients were enrolled and divided into three groups according to tertiles on basis of Lp(a) levels (11.48 mg/dL and 21.70 mg/dL). The incidence of major adverse cardiac events (MACEs), including cardiac death, revascularization due to myocardial ischemia, readmission due to angina, and nonfatal stroke, was evaluated. Subgroups were established according to the low-density lipoprotein cholesterol (LDL-C) level (70 mg/dL).

Results: During follow-up (median: 2.0 years), 69 MACEs occurred, and 76.81% of these patients underwent revascularization. The Lp(a) level in the MACE group was significantly higher than that in the non-MACE group (22.90 mg/dL vs. 14.10 mg/dL, P < 0.001). Kaplan-Meier analysis revealed that the incidence of adverse cardiovascular events was significantly higher in the high Lp(a) groups than in the low Lp(a) groups (P = 0.001), mainly because of the increased occurrence of revascularization irrespective of LDL-C level (<70 mg/dL; ≥70 mg/dL, both P < 0.05) rather than death, nonfatal stroke, or hospital readmission due to angina (both P > 0.05). The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) for Lp(a) in predicting the occurrence of MACE and revascularization were 0.664 and 0.668 respectively, both P < 0.05. Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with revascularization [medium Lp(a) category: HR (95% CI): 2.988 (1.164-7.671), P = 0.023; high Lp(a) category: HR (95% CI): 4.937 (2.023-12.052), P < 0.001].

Conclusion: Lp(a) was an independent predictor of revascularization in patients with ACS complicated with T2DM, regardless of LDL-C levels. This suggests that Lp(a) measurement may help identify high-risk diabetic patients with ACS.
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http://dx.doi.org/10.1080/03007995.2022.2078080DOI Listing
May 2022

Efficacy and Safety for the Use of Half-Dosed Pegylated Granulocyte Colony-Stimulating Factors in Preventing Febrile Neutropenia During Chemotherapy in Patients With Malignant Tumors: A Multicenter, Open-Labeled, Single-Arm Phase 2 Trial.

Front Oncol 2022 27;12:820324. Epub 2022 Apr 27.

Institute of Molecular Medicine and Experimental Immunology, University Clinic of Rheinische Friedrich-Wilhelms-University, Bonn, Germany.

Background: Prophylactic granulocyte-colony stimulating factor (G-CSF) has been shown to effectively prevent febrile neutropenia (FN) and grade 3/4 neutropenia during myelosuppressive treatment. The present study reports the clinical efficacy and safety of the prophylactic use of G-CSF with a half dose for cancer patients with an intermediate risk of FN combined with ≥1 patient-specific risk during multiple chemotherapy.

Methods: This multicenter, one-arm, and open-label clinical study involved 151 patients [median age, 54 years old (range, 46.0-62.5); 38.4% female] with malignant tumors, including >20 different cancers. These patients underwent a total of 604 cycles of chemotherapy and received a half dose of PEG-rhG-CSF administration prior to each cycle.

Results: The incidence rate of FN was 3.3% for this cohort during chemotherapy. Chemotherapy delay occurred in 6 (4.0%) patients for 12 (2.0%) cycles. Early termination of cancer treatment occurred in 14 (9.3%) patients. In this cohort, 23 (15.2%) patients required antibiotic use during courses of chemotherapy. A total of 28 (18.5%) patients experienced clear adverse effects during cancer treatment.

Conclusion: The prophylactic PEG-rhG-CSF with a half dose can both efficaciously and safely prevent neutropenia for patients of diverse cancers with an intermediate risk of FN combined with ≥1 patient-specific risk during chemotherapy.
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http://dx.doi.org/10.3389/fonc.2022.820324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095430PMC
April 2022

Demineralized Cortical Bone Matrix Augmented With Peripheral Blood-Derived Mesenchymal Stem Cells for Rabbit Medial Meniscal Reconstruction.

Front Bioeng Biotechnol 2022 27;10:855103. Epub 2022 Apr 27.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.

Tissue engineering is a promising treatment strategy for meniscal regeneration after meniscal injury. However, existing scaffold materials and seed cells still have many disadvantages. The objective of the present study is to explore the feasibility of peripheral blood-derived mesenchymal stem cells (PBMSCs) augmented with demineralized cortical bone matrix (DCBM) pretreated with TGF-β3 as a tissue-engineered meniscus graft and the repair effect. PBMSCs were collected from rabbit peripheral blood and subjected to three-lineage differentiation and flow cytometry identification. DCBM was prepared by decalcification, decellularization, and cross-linking rabbit cortical bone. Various characteristics such as biomechanical properties, histological characteristics, microstructure and DNA content were characterized. The cytotoxicity and the effects of DCBM on the adhesion and migration of PBMSCs were evaluated separately. The meniscus-forming ability of PBMSCs/DCBM complex induced by TGF-β3 was also evaluated at the molecular and genetic levels, respectively. Eventually, the present study evaluated the repair effect and cartilage protection effect of PBMSCs/DCBM as a meniscal graft in a rabbit model of medial meniscal reconstruction in 3 and 6 months. The results showed PBMSCs positively express CD29 and CD44, negatively express CD34 and CD45, and have three-lineage differentiation ability, thus can be used as tissue engineering meniscus seed cells. After the sample procedure, the cell and DNA contents of DCBM decreased, the tensile modulus did not decrease significantly, and the DCBM had a pore structure and no obvious cytotoxicity. PBMSCs could adhere and grow on the scaffold. Under induction of TGF-β3, PBMSCs/DCBM composites expressed glycosaminoglycan (GAG), and the related gene expression also increased. The results of the experiments that the PBMSCs/DCBM group had a better repair effect than the DCBM group and the control group at both 12 and 24 weeks, and the protective effect on cartilage was also better. Therefore, the application of DCBM augmented with PBMSCs for meniscus injury treatment is a preferred option for tissue-engineered meniscus.
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http://dx.doi.org/10.3389/fbioe.2022.855103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091599PMC
April 2022

Artificial Intelligence-Based Spiral CT 3D Reconstruction in Transcatheter Aortic Valve Implantation.

Comput Math Methods Med 2022 4;2022:5794681. Epub 2022 May 4.

Department of Catheterization Room, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000 Shandong, China.

To evaluate the clinical application effect of spiral computed tomography (CT) three-dimensional (3D) reconstruction based on artificial intelligence in transcatheter aortic valve implantation (TAVI), a CT 3D reconstruction model based on deep convolutional neural networks (DCNN) was established in this research, which was compared with the model-based iterative reconstruction (MBIR) and used in clinical practice. Then, 62 patients with aortic stenosis (AS) who underwent TAVI surgery were recruited as the research objects. The accuracy, sensitivity, and specificity of the multislice spiral CT scan (MSCT) and transthoracic echocardiography (TTE) in predicting the type of TAVI surgical valve were compared and analyzed. The results showed that the mean absolute error (MAE) (0.01) and root mean square error (RMSE) (0.086) of the MBIR model were higher than the reconstruction model in this research. The structural similarity (SSIM) (0.831) and peak signal-to noise ratio (PSNR) (32.77 dB) of the MBIR model were lower than the reconstruction model, and the differences were considerable ( < 0.05). Of the valve models selected based on the TTE measurement results, 35 cases were accurately predicted and 27 cases were incorrectly predicted. The accuracy of MSCT was 87.1%, the specificity was 98.84%, and the sensitivity was 92.87%; all of which were significantly higher than TTE ( < 0.05). In summary, compared with the MBIR reconstruction model, the imaging results of the model established in this research were closer to the real image. Compared with TTE, MSCT had higher accuracy, sensitivity, and specificity and can provide more accurate preoperative predictions for patients undergoing TAVI surgery.
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http://dx.doi.org/10.1155/2022/5794681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095377PMC
May 2022

Bioinspired Polyurethane Using Multifunctional Block Modules with Synergistic Dynamic Bonds.

ACS Macro Lett 2021 05 12;10(5):510-517. Epub 2021 Apr 12.

Key Laboratory of Functional Polymer Materials of Ministry of Education and College of Chemistry, Nankai University, Tianjin 300071, China.

Nature embraces an intriguing strategy to create high-performance biomaterials, such as spider silk which presents an unparalleled combination of stiffness, tensile strength, and toughness via hierarchical structures. However, to fabricate synthetic polymers with such excellent properties remains a challenging task. Inspired by the integration of multiblock backbone and densely H-bonding assemblies in spider silk as well as the delicate iron-catecholate complexes in mussel byssus, we proposed a novel molecular design with multifunctional block modules to obtain polymer materials that exhibit excellent mechanical property, self-healing ability, and reprocessability. It was achieved by introducing reversible iron-catechol (DOPA-Fe) cross-links and quadruple H-bonds bearing 2-ureido-4-[1]-pyrimidinone (UPy) dimers as multifunctional blocks into a segmented polyurethane backbone with urethane blocks and semicrystalline polycaprolactone (PCL) blocks. These two types of dynamic cross-linking knots served as the sacrificial bonds to dissipate energy efficiently under external stress burden, endowing the dual physical cross-linked networks with increased toughness and breaking elongation. Moreover, the DOPA-Fe complexes could increase the crystallization of PCL, leading to remarkably enhanced Young's modulus and tensile strength. Solid-state NMR revealed the formation of quadruple H-bonds in UPy dimers and the presence of DOPA-Fe complexes, which restricted the mobility of the mobile phase and enhanced the crystallinity of the PCL domain. This work provides a feasible way to develop bioinspired materials with self-healable and reprocessable features, in addition to balanced enhancement of both stiffness and toughness.
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http://dx.doi.org/10.1021/acsmacrolett.1c00054DOI Listing
May 2021

Inwardly rectifying potassium channels mediate polymyxin-induced nephrotoxicity.

Cell Mol Life Sci 2022 May 15;79(6):296. Epub 2022 May 15.

Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia.

Polymyxin antibiotics are often used as a last-line defense to treat life-threatening Gram-negative pathogens. However, polymyxin-induced kidney toxicity is a dose-limiting factor of paramount importance and can lead to suboptimal treatment. To elucidate the mechanism and develop effective strategies to overcome polymyxin toxicity, we employed a whole-genome CRISPR screen in human kidney tubular HK-2 cells and identified 86 significant genes that upon knock-out rescued polymyxin-induced toxicity. Specifically, we discovered that knockout of the inwardly rectifying potassium channels Kir4.2 and Kir5.1 (encoded by KCNJ15 and KCNJ16, respectively) rescued polymyxin-induced toxicity in HK-2 cells. Furthermore, we found that polymyxins induced cell depolarization via Kir4.2 and Kir5.1 and a significant cellular uptake of polymyxins was evident. All-atom molecular dynamics simulations revealed that polymyxin B spontaneously bound to Kir4.2, thereby increasing opening of the channel, resulting in a potassium influx, and changes of the membrane potential. Consistent with these findings, small molecule inhibitors (BaCl and VU0134992) of Kir potassium channels reduced polymyxin-induced toxicity in cell culture and mouse explant kidney tissue. Our findings provide critical mechanistic information that will help attenuate polymyxin-induced nephrotoxicity in patients and facilitate the design of novel, safer polymyxins.
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http://dx.doi.org/10.1007/s00018-022-04316-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108107PMC
May 2022

Gender difference in working from home and psychologicaldistress - A national survey of U.S. employees during the COVID-19 pandemic.

Ind Health 2022 May 16. Epub 2022 May 16.

Department of Environmental Health Sciences, Fielding School of Public Health, University of California Los Angeles, United States.

TheCOVID-19 pandemic has precipitated broad and extensive changes in the waypeople live and work. While the general subject of working from home hasrecently drawn increased attention, few studies have assessed genderdifferences in vulnerability to the potential mental health effects of workingfrom home. Using data from 1,585workers who participated in the Health, Ethnicity, and Pandemic (HEAP) study, anational survey conducted in the U.S. during the COVID-19 pandemic in October2020, associations of working from home with psychological distress wereexamined with weighted logistic regression among 1,585 workers and stratified bygender. It was found that workers who worked from home had higher odds ofpsychological distress (aOR and 95% CI = 2.62 [1.46, 4.70]) compared to workerswho did not work from home, adjusting for demographic factors, socioeconomicstatus, and health behaviors. In gender-stratified analyses, this positiveassociation between working from home and psychological distress was significantin women (aOR and 95% CI = 3.68 [1.68, 8.09]) but not in men. These resultshave implications for female workers' mental health in the transition towardsworking from home in the COVID-19 pandemic era.
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http://dx.doi.org/10.2486/indhealth.2022-0077DOI Listing
May 2022

Eu- and Tb-Based Coordination Complexes of Poly(-Isopropyl,-methylacrylamide---dimethylacrylamide) Copolymer: Synthesis, Characterization and Property.

Polymers (Basel) 2022 Apr 29;14(9). Epub 2022 Apr 29.

Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China.

This contribution reports the syntheses, structural analyses and properties of europium (Eu)- and terbium (Tb)-based coordination complexes of poly(-isopropyl,-methylacrylamide---dimethylacrylamide) (poly(iPMAm--DMAm)) copolymer, named as poly-Eu(III) and poly-Tb(III), respectively. In greater detail, poly(iPMAm--DMAm) is first prepared by random copolymerization of -isopropyl,-methylacrylamide (iPMAm) and -dimethylacrylamide (DMAm) via group transfer polymerization (GTP). Next, poly(iPMAm--DMAm) is used as the polymer matrix for chelating with Eu and Tb cations at its side amide groups, to produce poly-Eu(III) and poly-Tb(III). Their structural characterizations by FT-IR spectroscopy and XPS confirm the formation of polymeric complexes. The study on their fluorescence emission characteristics and luminescence lifetime demonstrates that Poly-Eu(III) shows four strong emission peaks at 578, 593, 622, and 651 nm, which are responsible for the electron transitions from the excited state to the multiplet (J = 0, 1, 2, 3) states, respectively, and poly-Tb(III) also displays four emission peaks at 489, 545, 588, and 654 nm, mainly due to the electron transitions of → (i = 6, 5, 4, 3). The luminescence lifetimes of poly-Eu(III) (τ) and poly-Tb(III) (τ) are determined to be 4.57 and 7.50 ms, respectively. In addition, in aqueous solutions, poly-Eu(III) and poly-Tb(III) are found to exhibit thermoresponsivity, with their cloud temperatures (s) locating around 36.4 and 36.8 °C, respectively. Finally, the cytotoxicity study on the human colon carcinoma cells LoVo and DLD1 suggests that the luminescent Eu and Tb in the chelated state with poly(iPMAm--DMAm) show much better biocompatibility and lower toxicity than their inorganic salts.
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http://dx.doi.org/10.3390/polym14091815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100629PMC
April 2022

Bioavailability Enhancement of Cepharanthine via Pulmonary Administration in Rats and Its Therapeutic Potential for Pulmonary Fibrosis Associated with COVID-19 Infection.

Molecules 2022 Apr 24;27(9). Epub 2022 Apr 24.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-β1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.
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http://dx.doi.org/10.3390/molecules27092745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104485PMC
April 2022

Public Interest, Risk, Trust, and Personal Protective Equipment Purchase and Usage: Face Masks Amid the COVID-19 Pandemic.

Int J Environ Res Public Health 2022 May 1;19(9). Epub 2022 May 1.

The College of Economics and Management, Huazhong Agricultural University, Wuhan 430070, China.

This analysis considers public interest in COVID-19-related issues as well as individuals' risk perception and trust in society in their demand for face masks during the pandemic. Through a national survey, we examine demand during both the outbreak and the recovery stage of the pandemic and differentiate demand into purchasing and usage. The examination allows us to observe the evolvement of demand over time and stockpiling. We find that public interest and risk perception had a more significant association with mask demand during the outbreak stage, and trust was more connected with mask demand during the recovery stage. While stocking was evident in both stages, consumers were much less price sensitive in the outbreak stage. Overall, the relationship between most factors and mask demand was smaller in the recovery stage. Our research is useful for policymakers to assess the creation and termination of temporary legislation to help manage the value chain of personal protective equipment during a major public health crisis.
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http://dx.doi.org/10.3390/ijerph19095502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101231PMC
May 2022

High-FOM Temperature Sensing Based on Hg-EIT-Like Liquid Metamaterial Unit.

Nanomaterials (Basel) 2022 Apr 19;12(9). Epub 2022 Apr 19.

School of Information and Communication Engineering, Sichuan Provincial Engineering Research Center of Communication Technology for Intelligent IoT, University of Electronic Science and Technology of China, Chengdu 611731, China.

High-performance temperature sensing is a key technique in modern Internet of Things. However, it is hard to attain a high precision while achieving a compact size for wireless sensing. Recently, metamaterials have been proposed to design a microwave, wireless temperature sensor, but precision is still an unsolved problem. By combining the high-quality factor (Q-factor) feature of a EIT-like metamaterial unit and the large temperature-sensing sensitivity performance of liquid metals, this paper designs and experimentally investigates an Hg-EIT-like metamaterial unit block for high figure-of-merit (FOM) temperature-sensing applications. A measured FOM of about 0.68 is realized, which is larger than most of the reported metamaterial-inspired temperature sensors.
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http://dx.doi.org/10.3390/nano12091395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103140PMC
April 2022

The Use of Molecular Dynamics Simulation Method to Quantitatively Evaluate the Affinity between HBV Antigen T Cell Epitope Peptides and HLA-A Molecules.

Int J Mol Sci 2022 Apr 22;23(9). Epub 2022 Apr 22.

Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China.

Chronic hepatitis B virus (HBV), a potentially life-threatening liver disease, makes people vulnerable to serious diseases such as cancer. T lymphocytes play a crucial role in clearing HBV virus, while the pathway depends on the strong binding of T cell epitope peptide and HLA. However, the experimental identification of HLA-restricted HBV antigenic peptides is extremely time-consuming. In this study, we provide a novel prediction strategy based on structure to assess the affinity between the HBV antigenic peptide and HLA molecule. We used residue scanning, peptide docking and molecular dynamics methods to obtain the molecular docking model of HBV peptide and HLA, and then adopted the MM-GBSA method to calculate the binding affinity of the HBV peptide-HLA complex. Overall, we collected 59 structures of HLA-A from Protein Data Bank, and finally obtained 352 numerical affinity results to figure out the optimal bind choice between the HLA-A molecules and 45 HBV T cell epitope peptides. The results were highly consistent with the qualitative affinity level determined by the competitive peptide binding assay, which confirmed that our affinity prediction process based on an HLA structure is accurate and also proved that the homologous modeling strategy for HLA-A molecules in this study was reliable. Hence, our work highlights an effective way by which to predict and screen for HLA-peptide binding that would improve the treatment of HBV infection.
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http://dx.doi.org/10.3390/ijms23094629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105472PMC
April 2022

Risk factors associated with preterm birth after IVF/ICSI.

Sci Rep 2022 May 13;12(1):7944. Epub 2022 May 13.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.

In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.
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http://dx.doi.org/10.1038/s41598-022-12149-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106684PMC
May 2022

Dietary Fiber Supplementation in Replacement Gilts Improves the Reproductive Performance From the Second to Fifth Parities.

Front Vet Sci 2022 26;9:839926. Epub 2022 Apr 26.

Institute of Animal Nutrition and Key Laboratory for Animal Disease-Resistance Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, China.

This study examined the effects of soluble fiber (SF) supplementation (0.8%), containing 17.4% rhamnose, 4.1% fucose, 11.1% arabinose, 30.6% xylose, and 16.4% galactose during the prepubescent phase on the subsequent performance from the second to fifth parities. After the first parity, 56 and 55 post-weaning sows in the control (CON) and SF groups had their reproductive performance monitored in succeeding parities. Circulating concentrations of anti-mullerian hormone (AMH) were greater in the SF group than in the CON group at 205 d of age and the first post-weaning day ( < 0.05). The SF treatment at the prepubescent phase resulted in an enhanced reproductive performance from parities three to five. In Parity three, the SF sows had 1.32 total born ( = 0.044), 1.43 born alive ( = 0.023) and 1.40 born effective, which was significantly more than in the CON group ( = 0.022). In Parity four, the SF sows had 1.1 total born ( = 0.058), 1.28 born alive ( = 0.019), and 1.06 born effective, significantly more than in the CON group ( = 0.049). In Parity five, the SF gilts had 1.43 total born ( = 0.075), 1.53 born alive ( = 0.067) and 1.65 born effective, significantly more than in the CON group ( = 0.020). No effects were observed for the removal of sows and backfat thickness at the mating in each parity between groups ( > 0.05). Collectively, gilts that received an extra 0.8% SF during the prepubescent phase increased their subsequent litter size as breeding sows. These results showed that nutritional decisions at the replacement phase could influence lifetime fertility.
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http://dx.doi.org/10.3389/fvets.2022.839926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088012PMC
April 2022

False-positive mpMRI and true-negative Ga-PSMA PET/CT xanthogranulomatous prostatitis: a case report.

Transl Androl Urol 2022 Apr;11(4):561-566

Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Xanthogranulomatous prostatitis (XGP) is a rare disorder of the prostate. It presents as a hard fixed nodule on digital rectal examination (DRE), and may cause obstructive urinary symptoms and elevated serum prostate-specific antigen (PSA) levels, therefore mimicking prostate cancer (PCa) clinically and biochemically. Radiological features of XGP overlap with those of PCa, and the 2 conditions cannot be distinguished by pelvic multiparametric magnetic resonance imaging (mpMRI). Ga-labelled prostate-specific membrane antigen (Ga-PSMA) with positron emission tomography/computed tomography (PET/CT) has shown its potential in the initial diagnosis and staging of PCa; however, the imaging characteristics of XGP on Ga-PSMA PET/CT have yet to be reported.

Case Description: We report the case of a 56-year-old man who had slowly progressing dysuria for 10 years, which was significantly worse for 1 week, and a PSA level of 49.19 ng/L. Ultrasound revealed a hypoechoic lesion in the left periphery of the prostate, which was hypointense with capsular irregularity on axial T2-weighted imaging (T2WI), hyperintense on the diffusion weighted imaging (DWI), and hypointense on the apparent diffusion coefficient (ADC) maps resulting in a Prostate Imaging-Reporting and Data System (PI-RADS) score of 5. The patient was highly suspected of having high-risk PCa and underwent a Ga-PSMA PET/CT for staging. The PET/CT images showed no PSMA uptake in the involved region. Considering that a small proportion of cases of PCa do not express PSMA, a subsequent targeted biopsy was performed, guided by mpMRI. Histopathological examination showed a large number of foamy macrophages in the neutrophile granulocyte infiltrate, and XGP was finally diagnosed. After treatment with antibiotic levofloxacin, the patient's PSA returned to normal, and his dysuria symptoms had disappeared at the 2-month follow-up.

Conclusions: Non-uptake of PSMA in a lesion may still provide information for a diagnosis by exclusion or regular follow-up checks in patients that are highly suspected to have PCa in clinic or on mpMRI.
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http://dx.doi.org/10.21037/tau-21-1068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085930PMC
April 2022

Dual-functional antitumor conjugates improving the anti-metastasis effect of combretastatin A4 by targeting tubulin polymerization and matrix metalloproteinases.

Eur J Med Chem 2022 May 5;238:114439. Epub 2022 May 5.

School of Pharmacy, Xinxiang Medical University, Xinxiang, 453003, China. Electronic address:

This study prepared different novel conjugates containing tubulin and MMP inhibitors and assessed their anticancer effects. Typically, the conjugate 15g, which contained combretastatin A4 (CA4) and 2-(4-((diethoxyphosphono)(o-tolyl)methylamino)phenyl)acetic acid (19g) connected by an ester bond, showed the maximum effect against proliferation. Particularly, the conjugate yielded a reduced IC value of 0.05 μM in controlling the proliferation of HepG2 cells compared to CA4 alone (0.09 μM). Systematic research indicated that 15g suppressed tubulin polymerization, induced cell cycle arrest at the G2/M phase, led to reactive oxidative stress (ROS) generation of HepG2 cells, and resulted in apoptosis by the mitochondrial-dependent apoptotic pathway. Moreover, 15g showed a potent effect on resistant metastasis by decreasing the levels of the proteins MMP2 and MMP9 in the HepG2 cells. Therefore, this conjugate is a potentially effective approach to improve the anti-metastatic effect of CA4 with high safety.
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http://dx.doi.org/10.1016/j.ejmech.2022.114439DOI Listing
May 2022

Research article: Three-year Follow-up of Neoadjuvant PD-1 inhibitor (Sintilimab) in Non-Small Cell Lung Cancer.

J Thorac Oncol 2022 May 9. Epub 2022 May 9.

Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Background: Programmed death receptor-1 (PD-1) inhibitors have been proved to be feasible and efficacy in multiple cancers, including non-small cell lung cancer (NSCLC). But few studies have evaluated the effectiveness of PD-1 inhibitor as neoadjuvant therapy with a long-term follow-up. Here, in this phase 1b study with a 3-year follow-up, we reported the clinical outcomes of patients who received the PD-1 inhibitor as neoadjuvant therapy.

Methods: Two doses of sintilimab (intravenously, 200 mg) were used for patients with stage IA-IIIB NSCLC (registration number: ChiCTR-OIC-17013726). Then surgery was performed within 29 to 43 days after the first dose. And all patients underwent positron emission tomography-computed tomography (PET-CT) at enrollment and before surgery to evaluate tumor metabolism after administration of PD-1 inhibitor. We also evaluated the expression of programmed cell death ligand 1 (PD-L1) as an exploratory analysis in 32 eligible patients. Safety was the primary endpoint. Overall survival (OS), disease-free survival (DFS), event survival (EFS), and major pathologic response (MPR) were the key secondary endpoints.

Results: With the mean 37.8 months follow-up, 3-year OS rates were 88.5% and the 3-year DFS rate was 75.0% among patients who underwent R0 resection. In patients with positive PD-L1 expression, 3-year OS and DFS rates were 95.5% and 81.8%, respectively. Eight patients had recurrent tumors, including local recurrence, lung metastasis, brain metastasis and bone metastasis. Patients with PD-L1 ≥ 1% had more favorable clinical outcomes than the other subgroup (HR, 0.275; 95% CI, 0.078 to 0.976). No more new adverse events (AEs) have occurred in the 3-year follow-up since we first reported them in the former publication.

Conclusions: This is the first study to report the long-term survival probability of NSCLC patients receiving PD-1 inhibitors as the neoadjuvant treatment. The three-year follow-up revealed that patients with positive PD-L1 expression and high tumor mutation burden have favorable clinical outcomes.
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http://dx.doi.org/10.1016/j.jtho.2022.04.012DOI Listing
May 2022

Comprehensive Analyses of Mutation-Derived Long-Chain Noncoding RNA Signatures of Genome Instability in Kidney Renal Papillary Cell Carcinoma.

Front Genet 2022 25;13:874673. Epub 2022 Apr 25.

Department of Pediatrics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

The role of long-chain noncoding RNA (lncRNA) in genomic instability has been demonstrated to be increasingly importance. Therefore, in this study, lncRNAs associated with genomic instability were identified and kidney renal papillary cell carcinoma (KIRP)-associated predictive features were analysed to classify high-risk patients and improve individualised treatment. The training ( = 142) and test ( = 144) sets were created using raw RNA-seq and patient's clinical data of KIRP obtained from The Cancer Genome Atlas (TCGA).There are 27 long-chain noncoding RNAs (lncRNAs) that are connected with genomic instability, these lncRNAs were identified using the 'limma' R package based on the numbers of somatic mutations and lncRNA expression profiles acquired from KIRP TCGA cohort. Furthermore, Cox regression analysis was carried out to develop a genome instability-derived lncRNA-based gene signature (GILncSig), whose prognostic value was confirmed in the test cohort as well as across the entire KIRP TCGA dataset. A GILncSig derived from three lncRNAs (BOLA3-AS1, AC004870, and LINC00839), which were related with poor KIRP survival, was identified, which was split up into high- and low-risk groups. Additionally, the GILncSig was found to be an independent prognostic predictive index in KIRP using univariate and multivariate Cox analysis. Furthermore, the prognostic significance and characteristics of GilncSig were confirmed in the training test and TCGA sets. GilncSig also showed better predictive performance than other prognostic lncRNA features. The function of lncRNAs in genomic instability and the genetic diversity of KIRP were elucidated in this work. Moreover, three lncRNAs were screened for prediction of the outcome of KIRP survival and novel insights into identifying cancer biomarkers related to genomic instability were discussed.
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http://dx.doi.org/10.3389/fgene.2022.874673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082950PMC
April 2022

The Long-Term Outcome in a Cohort of 52 Patients With Symptomatic Intramedullary Spinal Cavernous Hemangioma After Microsurgery and Emergency Rescue Surgery.

Front Med (Lausanne) 2022 25;9:872824. Epub 2022 Apr 25.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Background: Surgery is the mainstay treatment for patients with symptomatic intramedullary spinal cavernous hemangioma (ISCH), however the time of surgical intervention remains controversial. In this study, we proposed emergency rescue surgery (ERS) for patients in deteriorative type. The prognostic factors of patients with ISCH after microsurgery and the clinical effect of ERS were analyzed.

Methods: From January 2013 to November 2019, 52 patients with symptomatic ISCH treated by microsurgical treatment were collected, ranging in age from 17 to 66 years old (mean: 45.8 ± 13.5 years). The course of the disease ranged from 2 days to 20 years. Of 52 lesions, 17 lesions were in the cervical segment, 25 in the thoracic segment, and 10 in the lumbosacral segment; while seven cases were at the ventral surface, 25 cases at the dorsal surface, and 20 cases at the central spinal cord. The sagittal diameter ranged from 1 to 58 mm (median: 17.3 mm). The transverse diameter ratio ranged from 20 to 80% (median: 50.7%). Thirty-two patients were diagnosed as deteriorative type and 22 were treated by ERS.

Results: At 12 months after surgery, all patients were followed up, and no residual or recurrence was found in all patients. Twenty-five patients (48.1%) showed spinal cord functional improvement after surgery; 25 (48.1%) had no functional change; 2 (3.8%) got worse. For deteriorative patients, ERS group had a significantly higher improvement rate than the non-ERS group (χ = 5.393, = 0.02); For all 52 patients, the factors as a lesion at the ventral surface (Z = 10.453, = 0.015), or lumbosacral segment (χ = 9.259, = 0.010) and longer course of disease (Z = -2.021, = 0.043) were potential risks in functional recovery in univariate analysis; and in multiple-factor analysis, the lesion at the lumbosacral segment (OR = 4.004, 95% CI: 1.341~11.961, = 0.013) was the independent risk factors for the functional recovery.

Conclusions: Microsurgical resection is safe and effective for symptomatic ISCH. The ERS is an effective way to improve deteriorative patients' spinal cord function at long-term follow-up. The lesion at the lumbosacral segment is one of the poor prognostic factors.
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http://dx.doi.org/10.3389/fmed.2022.872824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084226PMC
April 2022

Supramolecular Detoxification of Macromolecular Biotoxin through the Complexation by a Large-Sized Macrocycle.

Adv Healthc Mater 2022 May 11:e2200270. Epub 2022 May 11.

Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin, 300387, P. R. China.

Biotoxins are diverse, complex, and hypertoxic, ultimately serving as grave and lasting menaces to humanity. Here, it is aimed to introduce a new detoxification methodology for macromolecular biotoxin through complexation by a very large macrocycle. A 25-mer peptide isolated from Lycosa erythrognatha spider venom (LyeTxI) is selected as the model macromolecular biotoxin. Quaterphen[4]arene, with a side length of ≈1.6 nm, has a sufficient cavity to bind LyeTxI. Hence, the water-soluble derivative of Quaterphen[4]arene (H) is designed and synthesized. H exhibits an overall host-guest complexation toward LyeTxI, resulting in a considerably high association constant of (7.01 ± 0.18) × 10  m . This encapsulation of peptide is interesting as traditional macrocycles can only engulf the amino acid residues of peptides due to their limited cavity size. In vitro assay verifies that complexation by H inhibits the interactions of LyeTxI with cell membranes, thereby reducing its cytotoxicity, suppressing hemolysis, and decreasing the release of lactate dehydrogenase. Notably, the intravenous administration of H has a significant therapeutic effect on LyeTxI-poisoned mice, alleviating inflammation and tissue damage, and markedly improving the survival rate from 10% to 80%. An efficient and potentially versatile approach is provided to detoxify macromolecular biotoxins, with giant macrocycle serving as an antidote.
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http://dx.doi.org/10.1002/adhm.202200270DOI Listing
May 2022

SNAIL Induces EMT and Lung Metastasis of Tumours Secreting CXCL2 to Promote the Invasion of M2-Type Immunosuppressed Macrophages in Colorectal Cancer.

Int J Biol Sci 2022 11;18(7):2867-2881. Epub 2022 Apr 11.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

There is increasing evidence that tumour-associated macrophages (TAMs) are critical in the formation of lung metastases. However, the molecular mechanisms of tumour interactions with TAMs via EMT are largely unknown. The mechanism of lung metastasis was studied in patient tissues. The mechanism of SNAIL regulation of the interaction between mesenchymal cells and M2 macrophages was elucidated using coculture of M2 macrophages and Transwell assays and in nude mice and NOD-SCID mice. We demonstrated for the first time that SNAIL and CXCL2 were abnormally overexpressed in colorectal cancer, especially lung metastasis, and were associated with poor prognosis in colorectal cancer patients. We demonstrated that SNAIL promoted the secretion of CXCL2 by mesenchymal cells and induced the activation of M2 macrophages. We found that CXCL2 attracted M2-type macrophages to infiltrate and promote tumour metastasis. These findings suggest that SNAIL promotes epithelial tumour transformation, and that transformed mesenchymal cells secrete CXCL2, which promotes M2 macrophage infiltration and tumour cell metastasis. These findings elucidate the tumour-TAM interaction in the metastatic microenvironment, which is mediated by tumour-derived CXCL2 and affects lung metastasis. This study also provides a theoretical basis for the occurrence of secondary lung cancer.
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http://dx.doi.org/10.7150/ijbs.66854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066124PMC
May 2022

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results.

Nat Med 2022 May 9. Epub 2022 May 9.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.

Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers ( NCT03874897 ). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 10, 3.75 × 10 or 5.0 × 10 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.
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http://dx.doi.org/10.1038/s41591-022-01800-8DOI Listing
May 2022
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