Publications by authors named "Yu Xia"

1,221 Publications

  • Page 1 of 1

Characterization of the immune cell infiltration landscape in myxofibrosarcoma to aid immunotherapy.

Front Immunol 2022 22;13:916915. Epub 2022 Jul 22.

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

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice.
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http://dx.doi.org/10.3389/fimmu.2022.916915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353264PMC
July 2022

SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US.

JAMA Oncol 2022 Aug 4. Epub 2022 Aug 4.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1001/jamaoncol.2022.3048DOI Listing
August 2022

Pyridine dicarbanion-bonded Ag organometallic nanoclusters: synthesis and on-surface oxidative coupling reaction.

Chem Sci 2022 Jul 14;13(27):8095-8103. Epub 2022 Jun 14.

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University Beijing 100084 China

Highly reactive organometallic nanoclusters generated in metal-catalyzed reactions are pivotal in the comprehension of catalytic mechanisms. Herein, we develop a two-step synthetic method to achieve three unprecedented aryl dicarbanion-bonded Ag nanoclusters by using protective macrocyclic ligands. Firstly, various aryl dicarbanion-Ag cluster intermediates are acquired a silver-mediated annulation reaction within a macrocyclic ligand. These Ag cluster precursors are released from the surrounding macrocycle by protonation, and further undergo an inter-cluster coupling to generate bipyridine products and low-valence silver atoms. The remaining resurgent diide-Ag clusters assemble with low-valence silver atoms to yield a series of organometallic Ag nanoclusters. These Ag nanoclusters feature a unique open-shell electronic structure as well as a chiral cluster architecture due to the asymmetric arrangements of surrounding aryl dianion ligands. Furthermore, the pyridyl diide ligands on the surface of the nanocluster further experience an intra-cluster oxidative coupling to produce bipyridine coupling products and large nanoparticles. The coupling reaction-driven cluster-to-cluster transformation is comprehensively tracked by high resolution mass spectroscopy. This work is not only reminiscent of the detailed evolution of cluster species upon the occurrence of coupling reactions, but also reproduces novel inter- and intra-cluster coupling steps at different reaction stages.
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http://dx.doi.org/10.1039/d2sc00989gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278448PMC
July 2022

Water-solid contact electrification causes hydrogen peroxide production from hydroxyl radical recombination in sprayed microdroplets.

Proc Natl Acad Sci U S A 2022 Aug 1;119(32):e2209056119. Epub 2022 Aug 1.

Department of Chemistry, Stanford University, Stanford, CA 94305.

Contact electrification between water and a solid surface is crucial for physicochemical processes at water-solid interfaces. However, the nature of the involved processes remains poorly understood, especially in the initial stage of the interface formation. Here we report that HO is spontaneously produced from the hydroxyl groups on the solid surface when contact occurred. The density of hydroxyl groups affects the HO yield. The participation of hydroxyl groups in HO generation is confirmed by mass spectrometric detection of O in the product of the reaction between 4-carboxyphenylboronic acid and O-labeled HO resulting from O plasma treatment of the surface. We propose a model for HO generation based on recombination of the hydroxyl radicals produced from the surface hydroxyl groups in the water-solid contact process. Our observations show that the spontaneous generation of HO is universal on the surfaces of soil and atmospheric fine particles in a humid environment.
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http://dx.doi.org/10.1073/pnas.2209056119DOI Listing
August 2022

Corrigendum to 'Building capacity for macrophage modulation and stem cell recruitment in high-stiffness hydrogels for complex periodontal regeneration: Experimental studies in vitro and in rats' [Acta Biomaterialia 88 (2019) 162-180].

Acta Biomater 2022 Jul 25. Epub 2022 Jul 25.

State Key Laboratory of Military Stomatology Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China; National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China; Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China. Electronic address:

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http://dx.doi.org/10.1016/j.actbio.2022.07.027DOI Listing
July 2022

The Transcription Factors and Synergistically Activate the Expression of in Wheat, Which Positively Regulates the Development of Microspore in .

Int J Mol Sci 2022 Jul 20;23(14). Epub 2022 Jul 20.

Key Laboratory of Crop Heterosis of Shaanxi Province, Wheat Breeding Engineering Research Center, Ministry of Education, College of Agronomy, Northwest A&F University, Yangling 712100, China.

Pollen fertility plays an important role in the application of heterosis in wheat ( L.). However, the key genes and mechanisms underlying pollen abortion in K-type male sterility remain unclear. is an essential gene for pollen development in wheat. Here, we explored the mechanism involved in its transcriptional regulation during pollen development, focusing on a 1315-bp promoter region. Several -acting elements were identified in the promoter, including binding motifs for AtAMS and AtMYB103 (CANNTG and CCAACC, respectively). Evolutionary analysis indicated that and were the homologs of and , respectively, and encoded nucleus-localized transcription factors containing 557 and 352 amino acids, respectively. and were specifically expressed in wheat anthers, and their expression levels were highest in the early uninucleate stage; this expression pattern was consistent with that of . Meanwhile, we found that TaTDRL and TaMYB03 directly interacted, as evidenced by yeast two-hybrid and bimolecular fluorescence complementation assays, while yeast one-hybrid and dual-luciferase assays revealed that both TaTDRL and TaMYB103 could bind the promoter and synergistically increase its transcriptional activity. Furthermore, TaTDRL-EAR and TaMYB103-EAR transgenic plants displayed abnormal microspore morphology, reduced pollen viability, and lowered seed setting rates. Additionally, the expression of , a homolog, was significantly lower in the two repressor lines than in the corresponding overexpression lines or WT plants. In summary, we identified a potential transcriptional regulatory mechanism associated with wheat pollen development.
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http://dx.doi.org/10.3390/ijms23147996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321142PMC
July 2022

Ameliorating Effects of against Intestinal Inflammation and Barrier Dysfunction Induced by High Fat Diet in Obese Mice.

Int J Mol Sci 2022 Jul 11;23(14). Epub 2022 Jul 11.

Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

Tripartite Motif 67 (TRIM67) is an important member of TRIM family proteins, which participates in different cellular processes including immune response, proliferation, differentiation, carcinogenesis, and apoptosis. In recent years, a high fat diet (HFD) has remained one of the main causes of different metabolic diseases and increases in intestinal permeability as well as inducing intestinal inflammation. The current study investigated the protective effects of in the ileum and colon of obese mice. 4-week-old wild-type (WT) C57BL/6N mice and knockout (KO) C57BL/6N mice were selected and randomly divided into four sub-groups, which were fed with control diet (CTR) or HFD for 14 weeks. Samples were collected at the age of 18 weeks for analysis. To construct an in vitro obesity model, over-expressed IPEC-J2 cells (porcine intestinal cells) with were stimulated with palmitic acid (PA), and its effects on the expression level of , inflammatory cytokines, and barrier function were evaluated. The KO mice showed pathological lesions in the ileum and colon and this effect was more obvious in KO mice fed with HFD. In addition, KO mice fed with a HFD or CTR diet had increased intestinal inflammation, intestinal permeability, and oxidative stress compared to that WT mice fed with these diets, respectively. Moreover, IPEC-J2 cells were transfected with TRIM67 plasmid to perform the same experiments after stimulation with PA, and the results were found consistent with the in vivo evaluations. Taken together, our study proved for the first time that HFD and KO mice have synergistic damaging effects on the intestine, while plays an important protective role in HFD-induced intestinal damage.
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http://dx.doi.org/10.3390/ijms23147650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317707PMC
July 2022

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201).

Front Oncol 2022 7;12:925236. Epub 2022 Jul 7.

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

Background: Nearly all anti-PD-1 antibodies are of the IgG4 isotype, and thus possess residual FcR effector functions. Such anti-PD-1 antibodies are also associated with immune tolerance and escape due to instability of the CH3 domain and Fc-Fc interaction. In this trial, we examined the efficacy and safety of penpulimab, a novel IgG1 anti-PD-1 antibody that does not bind to the Fc receptor, in patients with refractory or relapsed classical Hodgkin lymphoma (R/R cHL).

Methods: Adult patients (≥18 years of age) with R/R cHL received 200 mg penpulimab once biweekly until disease progression or unacceptable toxicities for a maximum of 24 months. The primary endpoint was objective response rate (ORR) based on the Independent Radiology Review Committee per Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs).

Results: A total of 94 patients were enrolled. The median follow-up was 15.8 months. The ORR was 89.4% (95% CI 80.8%, 95.0%) in the full analysis set (85 patients). Forty (47.1%) patients achieved complete remission, 36 (42.4%) patients achieved partial remission. The 12-month PFS rate was 72.1% (95% CI 60.5%, 80.8%) and the 18-month OS rate was 100%. Totally 97.9% (92/94) of patients experienced at least one TRAE. The rate of grade 3 and above TRAEs was 26.6% (25/94). In addition, 51 (54.3%) patients experienced an irAE, and 4 (4.3%) patients developed grade 3 or above irAEs. No irAE-related death occurred.

Conclusions: Penpulimab was effective and safe in patients with R/R cHL.
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http://dx.doi.org/10.3389/fonc.2022.925236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301139PMC
July 2022

Plant regeneration via callus-mediated organogenesis in commercial variety of Chuanbeichai No. 1 in DC.

Plant Biotechnol Rep 2022 Jul 16:1-11. Epub 2022 Jul 16.

School of Life Science and Engineering, Southwest University of Science and Technology, 59 Qinglong Road, Mianyang, 621010 Sichuan China.

DC is an important medicinal plant with many active ingredients that are used for the treatment of different types of diseases and valued in pharmaceutical markets. In vitro shoot regeneration can efficiently contribute to the improvement of In the present study, we investigated the effects of the explant type and plant growth regulators (PGRs) on embryogenic callus induction and plant regeneration in . Our investigation demonstrated that 2 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) combined with 1 mg/L thidiazuron (TDZ) played a major role in promoting callus induction from leaf, hypocotyl and stem 2 explants, whereas the most effective treatment for stem 1 callus formation was Murashige and Skoog (MS) medium supplemented with 1 mg/L 2,4-D, 0.5 mg/L 6-benzyladenine (BA) and 0.5 mg/L kinetin (Kin). The highest shoot regeneration rate (57.14%) was obtained from hypocotyl-induced calli in MS medium with 0.5 mg/L Kin after 12 weeks of cultivation. This regeneration protocol can be used in large-scale cultivation and may be useful for future genetic modifications of
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http://dx.doi.org/10.1007/s11816-022-00772-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288091PMC
July 2022

Xpert MTB/RIF Ultra outperformed the Xpert assay in tuberculosis lymphadenitis diagnosis: a prospective head-to-head cohort study.

Int J Infect Dis 2022 Jul 21. Epub 2022 Jul 21.

National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, Beijing, China. Electronic address:

Objectives: Xpert MTB/RIF Ultra (Xpert-Ultra) has shown better sensitivity in comparison with Xpert MTB/RIF (Xpert) in extra-pulmonary tuberculosis, while the head-to-head comparison of these methods in tuberculosis lymphadenitis had barely been performed.

Methods: Patients with undiagnosed lymphadenopathy were recruited prospectively and consecutively, and fine-needle aspirates biopsy (FNA) or lymph node tissue was collected. The specimen was subjected to smear, culture, Xpert and Xpert-Ultra assays. Culture and/or smear for AFB or AFB observed on histopathology were performed as a reference.

Results: 106 participants were recruited, including 41 confirmed TB, 33 probableTB and 32 non-TB lymphadenopathy. The head-to-head comparison for Mtb detection showed that Xpert-Ultra produced the highest sensitivity when compared with smear, culture and Xpert (75.7% vs. 5.4 %, 13.5% and 48.7%).When Xpert-Ultra outcomes were integrated for diagnosis, the percentage of confirmed TB lymphadenitis case increased from 55.4% (41/74) to 85.1% (63/74). The sensitivities of Xpert-Ultra and Xpert on tissue were 73.6% (95%CI,59.4-84.3) and 39.6% (95%CI,26.8-54.0), respectively. The sensitiviyt of Xpert-Ultra on FNA samples (81.0%,95%CI 57.4-93.7) was higher than that of Xpert (71.4%,95% CI 47.7-87.8).

Conclusions: Xpert-Ultra detected significantly more TB lymphadenitis cases than Xpert or culture. This superiority was particularly distinct using lymph node tissue than FNA detection.
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http://dx.doi.org/10.1016/j.ijid.2022.07.039DOI Listing
July 2022

Moraxella occupied the largest proportion in the nasal microbiome in healthy children, which potential protect them from COVID-19.

Microb Pathog 2022 Jul 21;170:105685. Epub 2022 Jul 21.

Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, PR China. Electronic address:

Background: In the prevalence of COVID-19, infection symptoms are different in children and adults. In this study to investigate the differences in the upper respiratory tract microbiome profile between healthy children and adults and to explore which microbiome protect them from COVID-19.

Methods: Thirty healthy children and 24 healthy adults were enrolled between October 2020 and January 2021. Nasal and throat swabs were obtained at enrollment, and DNA was extracted. We performed 16S rDNA sequencing to compare the alpha and beta diversity of the nasal and throat microbiomes between children and adults and assessed potential microbiome biomarkers.

Results: In the nasal microbiome, there were significant differences between healthy children and adults, and Moraxella occupied the largest proportion in healthy children. Notably, there was no significant difference between healthy children and adults in the throat microbiome, and it was predominated by Firmicutes. In the function analysis, compared with adults, there was increased enrichment in pathways related to amino acid metabolism and lipid metabolism, in children.

Conclusions: In the upper respiratory tract microbiome profiles, Moraxella may be involved in protecting children from COVID-19 infections and may be involved the amino acid metabolism and lipid metabolism.
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http://dx.doi.org/10.1016/j.micpath.2022.105685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299982PMC
July 2022

From functional genomics of vero cells to CRISPR-based genomic deletion for improved viral production rates.

Biotechnol Bioeng 2022 Jul 23. Epub 2022 Jul 23.

Department of Bioengineering, McGill University, Montreal, Québec, Canada.

Despite their wide use in the vaccine manufacturing field for over 40 years, one of the main limitations to recent efforts to develop Vero cells as high-throughput vaccine manufacturing platforms is the lack of understanding of virus-host interactions during infection and cell-based virus production in Vero cells. To overcome this limitation, this manuscript uses the recently generated reference genome for the Vero cell line to identify the factors at play during influenza A virus (IAV) and recombinant vesicular stomatitis virus (rVSV) infection and replication in Vero host cells. The best antiviral gene candidate for gene editing was selected using Differential Gene Expression analysis, Gene Set Enrichment Analysis and Network Topology-based Analysis. After selection of the ISG15 gene for targeted CRISPR genomic deletion, the ISG15 genomic sequence was isolated for CRISPR guide RNAs design and the guide RNAs with the highest knockout efficiency score were selected. The CRISPR experiment was then validated by confirmation of genomic deletion via PCR and further assessed via quantification of ISG15 protein levels by western blot. The gene deletion effect was assessed thereafter via quantification of virus production yield in the edited Vero cell line. A 70-fold and an 87-fold increase of total viral particles productions in ISG15 Vero cells was achieved for, respectively, IAV and rVSV while the ratio of infectious viral particles/total viral particles also significantly increased from 0.0316 to 0.653 for IAV and from 0.0542 to 0.679 for rVSV-GFP.
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http://dx.doi.org/10.1002/bit.28190DOI Listing
July 2022

A computational study of the HO + SO → HOSO + O reaction catalyzed by a water monomer, a water dimer and small clusters of sulfuric acid: kinetics and atmospheric implications.

Phys Chem Chem Phys 2022 Aug 3;24(30):18205-18216. Epub 2022 Aug 3.

Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.

Herein, the reaction mechanisms and kinetics for the HO + SO → HOSO + O reaction catalyzed by a water monomer, a water dimer and small clusters of sulfuric acid have been studied theoretically by quantum chemical methods and the Master Equation/Rice-Ramsperger-Kassel-Marcus (ME/RRKM) rate calculations. The calculated results show that when HO is introduced into the HO + SO reaction, it not only enhances the stability of the reactant complexes by 9.0 kcal mol but also reduces the energy of the transition state by 8.7 kcal mol. As compared with HO, catalysts (HO), HSO, HSO⋯HO and (HSO) are more effective energetically, which not only results from a higher binding energy of 21.3-26.0 kcal mol for the reactant complexes but also from a reduction of the energy of the transition states by 8.6-17.2 kcal mol. Effective rate constant calculations show that, as compared with HO, catalysts (HO), HSO, HSO⋯HO and (HSO) can never become more efficient catalysts within the altitude range of 0-15 km due to their relatively lower concentrations. Besides, at 0 km altitude, the enhancement factor for the HO and ('/) (HO)-assisted HO + SO reaction within the temperature range of 280-320 K was respectively calculated to be 0.31%-0.34% and 0.16%-0.27%, while the corresponding enhancement factor of HO and (HO) at higher altitudes of 5-15 km was respectively found only 0.002%-0.12% and 0.00001%-0.022%, indicating that the contributions of HO and (HO) are not apparent in the gas-phase reaction of HO with SO especially at higher altitude. Overall, the present work will give a new insight into how a water monomer, a water dimer and small clusters of sulfuric acid catalyze the HO + SO → HOSO + O reaction.
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http://dx.doi.org/10.1039/d1cp03318bDOI Listing
August 2022

S-1 and oxaliplatin combined with nanoparticle albumin-bound paclitaxel adjuvant chemotherapy for advanced gastric adenocarcinoma.

Chin Med J (Engl) 2022 Jul 22. Epub 2022 Jul 22.

First Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, China.

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http://dx.doi.org/10.1097/CM9.0000000000002003DOI Listing
July 2022

Dexamethasone Sensitizes Acute Monocytic Leukemia Cells to Ara-C by Upregulating FKBP51.

Front Oncol 2022 4;12:888695. Epub 2022 Jul 4.

Department of Central Laboratory, Shandong Provincial Hospital, Shandong University, Jinan, China.

In this study, we demonstrated that the expression of FK506 binding protein 51 (FKBP51) is upregulated in acute monocytic leukemia (AML-M5) cells by dexamethasone and aimed to investigate the possible effects of FKBP51 on the growth and cytarabine sensitivity of AML-M5 cells. THP-1 and U937cells were used to establish AML-M5 cell models with FKBP51 overexpression and knockdown, respectively. Cell proliferation, apoptosis and response to cytarabine were investigated by cell cycle, CCK-8 and Flow cytometry analyses. The mice experiment was conducted to detect the role of FKBP51 on AML-M5 cells proliferation and antileukemia effect of Ara-C/Dexamethasone co-therapy . Western blots were employed to determine protein expression levels. FKBP51 upregulation significantly attenuated THP-1 cell proliferation and sensitized the cells to cytarabine treatment which was further enhanced by dexamethasone. These effects were indicated by decreases in cell viability, S-G2/M phase cell cycle distribution, cytarabine 50% inhibitory concentration (IC50) values and increases in apoptosis and were supported by decreased phosphorylation levels of AKT, GSK3β and FOXO1A and decreased levels of BCL-2 and increased levels of P21 and P27. In contrast, FKBP51 knockdown led to excessive U937 cell proliferation and cytarabine resistance, as indicated by increased cell viability and S-G2/M phase cell cycle distribution, decreased apoptosis, increased phosphorylation levels of AKT, GSK3β and FOXO1A, and increased BCL-2 and decreased P21 and P27 expression. In addition, an AKT inhibitor blocked cell cycle progression and reduced cell viability in all groups of cells. Furthermore, SAFit2, a specific FKBP51 inhibitor, increased U937 cell viability and cytarabine resistance as well as AKT phosphorylation. In conclusion, FKBP51 decelerates proliferation and improves the cytarabine sensitivity of AML-M5 cells by inhibiting AKT pathways, and dexamethasone in combination with Ara-C improves the chemosensitivity of AML-M5.
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http://dx.doi.org/10.3389/fonc.2022.888695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290766PMC
July 2022

Non-antibiotics matter: Evidence from a one-year investigation of livestock wastewater from six farms in East China.

Sci Total Environ 2022 Jul 16;846:157418. Epub 2022 Jul 16.

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

Livestock wastewater is an important source of pharmaceuticals in aquatic environments; however, most related studies only focused on antibiotics. This study investigated 18 pharmaceutical active compounds (PhACs), including 12 antibiotics and 6 non-antibiotics, in livestock wastewater during a one-year survey of six livestock farms in East China. The results showed that four non-antibiotic PhACs-caffeine, N,N-diethyl-m-toluamide, gemfibrozil, and diclofenac-exhibited high detection frequencies (80% to 97%), high concentrations (median 0.43 to 3.79 μg/L), poor removal efficiencies (3% to 53%), and high environmental risks. A ranking system was developed to prioritize PhACs based on their occurrence, removal, and environmental risks in livestock wastewater; diclofenac, N,N-diethyl-m-toluamide, sulfamethazine, sulfadiazine, and gemfibrozil, were identified as the top five priority PhACs that should be considered first. Finally, a preliminary source apportionment protocol using four priority PhACs was proposed to trace the emission originating from treated and untreated livestock wastewater and to indicate the major contributor (cattle or swine farms) in the region. To the best of our knowledge, this is the first long-term investigation on the pollution characteristics of non-antibiotics in livestock wastewater in China, and our findings highlight the importance of considering non-antibiotics and the prioritized PhACs for the pollution control of PhACs in livestock wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157418DOI Listing
July 2022

Structural Determinants of Yeast Protein-Protein Interaction Interface Evolution at the Residue Level.

J Mol Biol 2022 Jul 16;434(19):167750. Epub 2022 Jul 16.

Department of Bioengineering, Faculty of Engineering, McGill University, Montreal, QC, Canada. Electronic address:

Interfaces of contact between proteins play important roles in determining the proper structure and function of protein-protein interactions (PPIs). Therefore, to fully understand PPIs, we need to better understand the evolutionary design principles of PPI interfaces. Previous studies have uncovered that interfacial sites are more evolutionarily conserved than other surface protein sites. Yet, little is known about the nature and relative importance of evolutionary constraints in PPI interfaces. Here, we explore constraints imposed by the structure of the microenvironment surrounding interfacial residues on residue evolutionary rate using a large dataset of over 700 structural models of baker's yeast PPIs. We find that interfacial residues are, on average, systematically more conserved than all other residues with a similar degree of total burial as measured by relative solvent accessibility (RSA). Besides, we find that RSA of the residue when the PPI is formed is a better predictor of interfacial residue evolutionary rate than RSA in the monomer state. Furthermore, we investigate four structure-based measures of residue interfacial involvement, including change in RSA upon binding (ΔRSA), number of residue-residue contacts across the interface, and distance from the center or the periphery of the interface. Integrated modeling for evolutionary rate prediction in interfaces shows that ΔRSA plays a dominant role among the four measures of interfacial involvement, with minor, but independent contributions from other measures. These results yield insight into the evolutionary design of interfaces, improving our understanding of the role that structure plays in the molecular evolution of PPIs at the residue level.
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http://dx.doi.org/10.1016/j.jmb.2022.167750DOI Listing
July 2022

Fatigue Cracking Evolution and Model of Cold Recycled Asphalt Mixtures during Different Curing Times.

Materials (Basel) 2022 Jun 24;15(13). Epub 2022 Jun 24.

State Key Laboratory of High Performance Civil Engineering Materials, Jiangsu Research Institute of Building Science, Nanjing 210008, China.

This paper aims to investigate the fatigue cracking evolution of cold recycled asphalt mixtures with asphalt emulsion (CRME) under different curing times. The fatigue cracking model of CRME based on damage mechanics and fracture mechanics was analyzed according to the fatigue loading curve. Firstly, the fatigue cracking evolution of CRME was studied through an SCB strength test and SCB fatigue test. Then, the fatigue damage mechanics were used to establish a nonlinear fatigue cracking model, and the damage degree of CRME at the initial cracking point was determined. The Paris formula was used to characterize the law of fatigue crack propagation. Finally, the microstructure of CRME was observed by scanning electron microscopy (SEM) with the backscattering method. The results indicate that the initial cracking point appears at around 60% of the fatigue life according to the SCB fatigue test by means of image analysis. The damage variable was obtained through the cracking model, and the value of the damage variable was determined as 0.06-0.17 at the initial cracking point. In addition, the Paris formula showed that the crack growth of CRME can be reflected by the stress intensity factor and correlative parameters. Moreover, cement hydration products were mixed with the asphalt membrane to form a denser spatial structure during the curing process, which may provide higher fatigue performance of CRME. This research may provide a theoretical reference for studying the fatigue cracking behavior of CRME.
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http://dx.doi.org/10.3390/ma15134476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267167PMC
June 2022

Loss of TRIM67 Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease.

Int J Mol Sci 2022 Jul 5;23(13). Epub 2022 Jul 5.

Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

Obesity is considered as a major cause for the development and progress of non-alcoholic fatty liver disease (NAFLD), which is one of the most prevalent chronic liver diseases worldwide. However, molecular mechanisms that implicate in obesity-driven pathophysiology of NAFLD are not well defined. Here, we report a tripartite motif (TRIM) protein family member-TRIM67-that is hardly expressed in liver but is inducible on obese conditions. Enhanced expression of TRIM67 activates hepatic inflammation to disturb lipid metabolic homeostasis and promote the progress of NAFLD induced by obesity, while the deficiency in TRIM67 is protective against these pathophysiological processes. Finally, we show that the important transcription coactivator PGC-1α implicates in the response of hepatic TRIM67 to obesity.
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http://dx.doi.org/10.3390/ijms23137475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267895PMC
July 2022

I-mediated Csp-P bond formation tandem cyclization of -alkynylphenyl isothiocyanates with organophosphorus esters.

RSC Adv 2022 Jun 20;12(28):18072-18076. Epub 2022 Jun 20.

College of Chemistry and Chemical Engineering, Jiangxi Normal University Nanchang 330022 People's Republic of China

A novel, I-mediated tandem cyclization of -alkynylphenyl isothiocyanates with organophosphorus esters has been developed under mild conditions. Different kinds of 4-benzo[][1,3]thiazin-2-ylphosphonate could be synthesized in moderate to excellent yields. This method has the advantages of easy access to raw materials, free-metal catalyst, simple operation, high yield and high functional group tolerance.
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http://dx.doi.org/10.1039/d2ra03072aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207709PMC
June 2022

Cross-Tissue Analysis Using Machine Learning to Identify Novel Biomarkers for Knee Osteoarthritis.

Comput Math Methods Med 2022 23;2022:9043300. Epub 2022 Jun 23.

Department of Orthopaedics, Hospital of Chengdu University of Traditional Chinese Medicine, 610075, China.

Background: Knee osteoarthritis (KOA) is a common degenerative joint disease. In this study, we aimed to identify new biomarkers of KOA to improve the accuracy of diagnosis and treatment.

Methods: GSE98918 and GSE51588 were downloaded from the Gene Expression Omnibus database as training sets, with a total of 74 samples. Gene differences were analyzed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Disease Ontology enrichment analyses for the differentially expressed genes (DEGs), and GSEA enrichment analysis was carried out for the training gene set. Through least absolute shrinkage and selection operator regression analysis, the support vector machine recursive feature elimination algorithm, and gene expression screening, the range of DEGs was further reduced. Immune infiltration analysis was carried out, and the prediction results of the combined biomarker logistic regression model were verified with GSE55457.

Results: In total, 84 DEGs were identified through differential gene expression analysis. The five biomarkers that were screened further showed significant differences in cartilage, subchondral bone, and synovial tissue. The diagnostic accuracy of the model synthesized using five biomarkers through logistic regression was better than that of a single biomarker and significantly better than that of a single clinical trait.

Conclusions: CX3CR1, SLC7A5, ARL4C, TLR7, and MTHFD2 might be used as novel biomarkers to improve the accuracy of KOA disease diagnosis, monitor disease progression, and improve the efficacy of clinical treatment.
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http://dx.doi.org/10.1155/2022/9043300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246600PMC
July 2022

Transseptal Approach Versus Transaortic Approach for Catheter Ablation of Left-Sided Accessory Pathways in Children.

Front Pediatr 2022 17;10:888029. Epub 2022 Jun 17.

Department of Cardiology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Background: Catheter ablation is recommended to eradicate supraventricular tachycardia caused by left-sided accessory pathways (APs) in children. This study aims to compare the safety and efficacy of the transseptal approach (TS) and aortic approach (TA) for catheter ablation of left-sided APs in a pediatric cohort.

Methods: Patients < 18 years of age with left-sided APs who had undergone ablation at Beijing Children's Hospital between 13 January 2018 and 7 January 2020 were included and randomly categorized into either TS or TA group (follow-up for 22 months). In all, 60 patients in TS group and 41 patients in TA group were included in this study. Principal endpoints were success rate, recurrence rate, complications, procedure time, and radiation dose.

Results: For TS group versus TA group, success rate was observed in 100 versus 97.56% ( = 0.402). The procedure time was 27.0 (32.0-23.0) versus 29.0 (38.0-24.5) min ( = 0.092). The rate of success or the procedure time was similar, but for the patients with Aps located in left posterior septum (LPS) or left posterior lateral (LPL), the TS group had a shorter procedure time compared with TA group ( < 0.01). The radiation dose was 28.0 (20.0-41.75) versus 0 mGy ( < 0.001). After successful ablation, no recurrence and complication were observed in either group.

Conclusion: Both TS and TA for catheter ablation of left-sided Aps were shown to be safe and effective in children. Zero radiation and ease of mastery make TA the preferred choice. TS is recommended to be used by properly trained medical professionals, especially for patient with AP localized in the LPL or LPS. However, TS is a good alternative where patients have aortic lesions or when TA fails.
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http://dx.doi.org/10.3389/fped.2022.888029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247647PMC
June 2022

Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome.

J Cell Mol Med 2022 Aug 29;26(15):4357-4370. Epub 2022 Jun 29.

Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Shandong University, Jinan, China.

Obstetric antiphospholipid syndrome (OAPS) is mediated by antiphospholipid antibodies (aPLs, and anti-β2 glycoprotein I antibody is the main pathogenic antibody), and recurrent abortion, preeclampsia, foetal growth restriction and other placental diseases are the main clinical characteristics of placental pathological pregnancy. It is a disease that seriously threatens the health of pregnant women. Hydroxychloroquine (HCQ) was originally used as an anti-malaria drug and has now shown benefit in refractory OAPS where conventional treatment has failed, with the expectation of providing protective clinical benefits for both the mother and foetus. However, its efficacy and mechanism of action are still unclear. After clinical data were collected to determine the therapeutic effect, human trophoblast cells in early pregnancy were prepared and treated with aPL. After the addition of HCQ, the proliferation, invasion, migration and tubule formation of the trophoblast cells were observed so that the therapeutic mechanism of HCQ on trophoblast cells could be determined. By establishing an obstetric APS mouse model similar to the clinical situation, we were able to detect the therapeutic effect of HCQ on pathological pregnancy. The normal function of trophoblast cells is affected by aPL. Antibodies reduce the ability of trophoblast cells to invade and migrate and can impair tubule formation, which are closely related to placental insufficiency. HCQ can partially reverse these side effects. In the OAPS mouse model, we found that HCQ prevented foetal death and reduced the incidence of pathological pregnancy. Therefore, HCQ can improve pregnancy outcomes and reverse the aPL inhibition of trophoblast disease. In OAPS, the use of HCQ needs to be seriously considered.
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http://dx.doi.org/10.1111/jcmm.17459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344817PMC
August 2022

Bone Volumetric Density, Microarchitecture, and Estimated Bone Strength in Tumor-Induced Rickets/Osteomalacia X-linked Hypophosphatemia in Chinese Adolescents.

Front Endocrinol (Lausanne) 2022 13;13:883981. Epub 2022 Jun 13.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

Tumor-induced rickets/osteomalacia (TIR/O) severely impairs bone microarchitecture and bone strength. However, no study has described the microarchitectural quality of bone in adolescent patients with TIR/O. TIR/O affects bone quality more severely than the inherited causes of hypophosphatemia, the most common form of which is X-linked hypophosphatemia (XLH). Nevertheless, differences of the microarchitectural quality of the bone between TIR/O and XLH have never been clarified. Therefore, in this study, we used high-resolution peripheral quantitative computed tomography to assess bone microarchitecture in five Chinese adolescent TIR/O patients, and these were compared with 15 age- and gender-matched XLH patients as well as 15 age- and gender-matched healthy controls. Compared with the healthy controls, the TIR/O patients presented with significantly lower volumetric bone mineral densities (vBMDs), severely affected bone microarchitecture, and profoundly weaker bone strength. The distal tibia was more severely affected than the distal radius. Compared with the XLH patients, the TIR/O patients showed deteriorated bone quality notably at the distal tibia and in the cancellous compartment, reflected by 45.9% lower trabecular vBMD ( = 0.029), 40.2% lower trabecular fraction ( = 0.020), 40.6% weaker stiffness ( = 0.058), and 42.7% weaker failure load ( = 0.039) at the distal tibia. The correlation analysis showed that a higher level of serum FGF23 and a lower level of serum phosphate were associated with a poorer bone microarchitecture and a weaker estimated bone strength in the hypophosphatemic patients of our study. In conclusion, our study demonstrated significantly lower vBMDs, severely impaired bone microarchitecture, and profoundly weaker bone strength in Chinese adolescent patients with TIR/O, notably at the distal tibia, compared with the same parameters in age- and sex-matched healthy controls and XLH patients, which was possibly caused by excessive FGF23 production and secretion, chronically severe hypophosphatemia, and weak mechanical stimulus at the lower extremities. These findings further our understanding of the impact of different kinds of hypophosphatemic rickets/osteomalacia on bone quality.
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http://dx.doi.org/10.3389/fendo.2022.883981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234144PMC
July 2022

Cyclin-Dependent Kinase Inhibitors Function as Potential Immune Regulators Inducing Pyroptosis in Triple Negative Breast Cancer.

Front Oncol 2022 8;12:820696. Epub 2022 Jun 8.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Immunotherapy is the most promising treatment in triple-negative breast cancer (TNBC), and its efficiency is largely dependent on the intra-tumoral immune cells infiltrations. Thus, novel ways to assist immunotherapy by increasing immune cell infiltrations were highly desirable.

Methods: To find key immune-related genes and discover novel immune-evoking molecules, gene expression profiles of TNBC were downloaded from Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identified hub genes. The CMap database was used subsequently to predicate potential drugs that can modulate the overall hub gene expression network. experiments were conducted to assess the anti-tumor activity and the pyroptosis phenotypes induced by GW-8510.

Results: Gene expression profiles of 198 TNBC patients were downloaded from GEO dataset GSE76124, and ssGSEA was used to divide them into Immune Cell Proficiency (ICP) group and Immune Cell Deficiency (ICD) group. Hub differential expressed gene modules between two groups were identified by WGCNA and then annotated by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A cyclin-dependent kinase (CDK) 2 inhibitor, GW-8510 was then identified by the CMap database and further investigated. Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, and studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials.

Conclusion: GW-8510, as well as other CDK inhibitors, might serve as potential immune regulators and pyroptosis promotors in TNBC.
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http://dx.doi.org/10.3389/fonc.2022.820696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213695PMC
June 2022

Analysis of fermentation control factors on volatile compounds of primary microorganisms in Jiang-flavor Daqu.

J Food Biochem 2022 Jun 24:e14277. Epub 2022 Jun 24.

College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Chinese Jiang-flavor Baijiu is the most widely consumed liquor. Jiang-flavor Daqu, a fermentation starter, is important sources of key flavors of Jiang-flavor Baijiu. Some microbes play significant roles in flavor formation of Daqu. In order to clarify the microbial population that promotes the formation of Daqu flavor, we use high throughput sequencing technology combined with headspace solid-phase microextraction gas chromatography-mass spectrometry to investigate microbial population and volatile compounds in Jiang-flavor Daqu. In addition, the dynamic changes of physicochemical factors and enzyme activities in Jiang-flavor Daqu were investigated. Correlations between microbial population, volatile compounds, physicochemical factors, and enzyme activities of Jiang-flavor Daqu were disclosed by redundancy analysis and Spearman correlation analysis. A total of 66 volatile compounds were identified and 14 primary microorganisms were selected. Results showed that high temperature environment could promote the formation of acids, aldehydes and ketones, phenols, furans by affecting the growth of Monascus, Trichomonascus, Cutaneotrichosporon, Wallemia, Millerozyma, Nigrospora, Cladosporium, Bacillus, and Pediococcus in the early fermentation stage. While high nitrogen environment was more suitable for the growth of Virgibacillus and Kroppenstedtia, who could promote the formation of pyrazines in the late fermentation stage. PRACTICAL APPLICATIONS: This study has provided a scientific basis for the directed regulation of Daqu fermentation through physicochemical factors, developed scientific basis for artificially constructing Daqu microbial population and obtaining an easy-to-operate, reproducible fermentation system for Daqu production.
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http://dx.doi.org/10.1111/jfbc.14277DOI Listing
June 2022

Comparative efficacy and safety of therapeutics for elderly glioblastoma patients: A Bayesian network analysis.

Pharmacol Res 2022 Aug 17;182:106316. Epub 2022 Jun 17.

Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China; China Pituitary Disease Registry Center, Chinese Pituitary Adenoma Cooperative Group, Beijing, PR China; China Alliance of Rare Diseases, Beijing, PR China. Electronic address:

Optimal management strategies for elderly glioblastoma (GBM) patients remain elusive. Overall survival (OS) and progression-free survival (PFS) in elderly newly diagnosed GBM (ndGBM) patients were analyzed with random-effects Bayesian network meta-analysis with the estimated hazard ratio (HR) with a 95% confidence interval (95% CrI). In addition, OS, PFS and adverse event (AE) data on ndGBM and recurrent GBM (rGBM) were assessed. Seventeen eligible trials with 12 on ndGBM and 5 on rGBM were identified. For the improvements it induced in the OS of elderly ndGBM patients, tumor treating field (TTF) + temozolomide (TMZ) (HR: 0.11, 95% CrI: 0.02-0.67 vs. supportive care (SPC)) ranked first, followed by TMZ + hyperfractionated radiotherapy (HFRT) (HR: 0.17, 95% CrI: 0.03-0.95 vs. SPC). For the improvements it induced in the PFS of elderly ndGBM patients, bevacizumab (BEV) + HFRT ranked first, followed by TMZ + HFRT. TMZ was observed to be more effective in O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated ndGBM patients than HFRT and standard radiotherapy (STRT). For elderly rGBM patients, the treatments included were comparable. The rates of other neurological symptoms (16.1%) and lymphocytopenia (10.4%) were higher in ndGBM patients; lymphocytopenia (10.3%) and infection (8.1%) were higher in rGBM patients among the ≥ 3 grade AEs. TMZ-related AEs should be further considered. In conclusion, TTF + adjuvant TMZ and TMZ + HFRT are most likely to be recommended for elderly ndGBM patients. No best treatment for rGBM in elderly patients is illustrated. TMZ is identified to be more effective in elderly ndGBM patients with methylated MGMT status; however, AEs associated with TMZ-related therapy should be well considered and managed.
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http://dx.doi.org/10.1016/j.phrs.2022.106316DOI Listing
August 2022

Prevention of catheter tip malposition with an ultrasound-guided finger-pressure method to block the internal jugular vein during PICC placement: a meta-analysis.

Wideochir Inne Tech Maloinwazyjne 2022 Jun 4;17(2):289-298. Epub 2022 Apr 4.

Department of Infection Management, The First People's Hospital of Jiangxia District, Hubei, Wuhan, China.

Introduction: Peripherally inserted central catheters (PICC) are a type of deep venipuncture, for which the catheter tip malposition rate is high.

Aim: To examine the feasibility of preventing catheter tip malposition during PICC placement using an ultrasound-guided finger-pressure method to block the internal jugular vein.

Material And Methods: We conducted a double-blinded randomized controlled trial (RCT) at a tertiary public hospital in Hubei province, China. A total of 600 patients were recruited and randomly allocated to the ultrasound-guided finger compression method (UGFCM) and traditional partial head method (TPHM) group (n = 300/group). Incidence of catheter tip malposition was assessed as the primary outcome of the study. A systematic literature review and meta-analysis was performed. We searched MEDLINE, EMBASE, Cochrane Library, China-National Knowledge Infrastructure, and Chinese Biomedicine Database and performed publication bias and sensitivity analyses on 10 extracted studies.

Results: There were no significant differences in baseline demographic and clinical characteristics between the two groups (p > 0.05). Overall incidence of catheter tip malposition was significantly lower in the UGFCM and TPHM group (1.67% vs. 10.3%) and particularly the incidence of malposition in the internal jugular vein (1% vs. 9%). In the meta-analysis of 10 eligible studies, with 1263 cases using the UGFCM method while 1261 adopted the TPHM method, the results showed that the incidence of catheter tip malposition was significantly lower in the group using the UGFCM method (OR = 0.17, 95% CI: 0.11-0.27, p < 0.01), which is in line with the results of our RCT study.

Conclusions: This study may add valuable evidence on adopting the finger-pressure method for blocking neck veins to reduce the incidence of catheter tip malposition, particularly in the internal jugular vein.
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http://dx.doi.org/10.5114/wiitm.2022.115198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186083PMC
June 2022

The pleiotropic roles of adipocyte secretome in remodeling breast cancer.

J Exp Clin Cancer Res 2022 Jun 14;41(1):203. Epub 2022 Jun 14.

Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.

Background: Breast cancer is the leading female cancer type and the cause of cancer-related mortality worldwide. Adipocytes possess important functions of energy supply, metabolic regulation, and cytokine release, and are also the matrix cell that supports mammary gland tissue. In breast cancer tumor microenvironment (TME), adipocytes are the prominent stromal cells and are implicated in inflammation, metastatic formation, metabolic remodeling, and cancer susceptibility.

Main Body: It is well-established that adipocyte secretome is a reservoir engaged in the regulation of tumor cell behavior by secreting a large number of cytokines (IL-6, IL-8, and chemokines), adipokines (leptin, adiponectin, autotaxin, and resistin), lipid metabolites (free fatty acids and β-hydroxybutyrate), and other exosome-encapsulated substances. These released factors influence the evolution and clinical outcome of breast cancer through complex mechanisms. The progression of breast cancer tumors revolves around the tumor-adipose stromal network, which may contribute to breast cancer aggressiveness by increasing the pro-malignant potential of TME and tumor cells themselves. Most importantly, the secretome alterations of adipocytes are regarded as distinctly important targets for breast cancer diagnosis, treatment, and drug resistance.

Conclusion: Therefore, this review will provide a comprehensive description of the specific adipocyte secretome characteristics and interactions within TME cell populations, which will enable us to better tailor strategies for tumor stratification management and treatment.
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http://dx.doi.org/10.1186/s13046-022-02408-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199207PMC
June 2022
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