Publications by authors named "Qian Zhu"

496 Publications

Deciphering the role of extracellular polymeric substances in the regulation of microbial extracellular electron transfer under low concentrations of tetracycline exposure: Insights from transcriptomic analysis.

Sci Total Environ 2022 May 22:156176. Epub 2022 May 22.

School of Environment and Energy, Guangdong Provincial Key Laboratory of Solid Wastes Pollution Control and Recycling, South China University of Technology, Guangzhou, Guangdong 510006, China.

Low concentrations of antibiotics can regulate the formation of electroactive biofilms, however, the underlying mechanisms, especially the composition and spatial distribution of extracellular polymeric substances (EPS) and their effects on extracellular electron transfer (EET) process, have not been fully deciphered. Here, the response of EPS of Geobacter sulfurreducens biofilm to low concentrations of tetracycline (μg L to mg L) was explored, and the impact of such EPS variations on EET efficiency was further elucidated by transcriptomic analysis. Results showed that 0.05 mg L of tetracycline achieved both beneficial quantitative and spatial regulation of redox-active proteins and non-conducting exopolysaccharides in EPS, while higher concentrations induced negative effects. Moreover, 1 mg L of tetracycline upregulated multiple exopolysaccharide biosynthesis-related genes, indicating a stress response for cell-protection, while 0.05 mg L of tetracycline upregulated most direct EET-related gene expressions, resulting in the promoted EET efficiency. Furthermore, 0.05 mg L of tetracycline selectively enriched Geobacter (45.55% vs 19.55% in control, respectively) from mixed inoculum. This research provides a new insight of how antibiotics at low concentrations regulated EET process through modulation of EPS.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156176DOI Listing
May 2022

Progress Toward a Universal Biomedical Data Translator.

Clin Transl Sci 2022 May 25. Epub 2022 May 25.

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.

Clinical, biomedical, and translational science has reached an inflection point in the breadth and diversity of available data and the potential impact of such data to improve human health and well-being. However, the data are often siloed, disorganized, and not broadly accessible due to discipline-specific differences in terminology and representation. To address these challenges, the Biomedical Data Translator Consortium has developed and tested a pilot knowledge graph-based 'Translator' system capable of integrating existing biomedical data sets and 'translating' those data into insights intended to augment human reasoning and accelerate translational science. Having demonstrated feasibility of the Translator system, the Translator program has since moved into development, and the Consortium has made significant progress in the research, design, and implementation of an operational system. Herein, we describe the current system's architecture, performance, and quality of results. We apply Translator to several real-world use cases developed in collaboration with subject-matter experts. Finally, we discuss the scientific and technical features of Translator and compare those features to other state-of-the-art biomedical graph-based question-answering systems.
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http://dx.doi.org/10.1111/cts.13301DOI Listing
May 2022

Oceanisphaera pacifica sp. nov., isolated from the intestine of Trichiurus japonicus.

Arch Microbiol 2022 May 19;204(6):338. Epub 2022 May 19.

Marine College, Shandong University, Weihai, 264209, Shandong, People's Republic of China.

A Gram-stain-negative, strictly aerobic, non-flagellated, oxidase- and catalase-positive, rod-shaped marine bacterium, designated strain DM8, was isolated from the intestine of Trichiurus japonicus in Weihai, China. The strain optimally grew at 25-35℃, with 1.0-4.0% (w/v) NaCl and at pH 7.0-8.0. Its colonies were circular, slightly yellow, non-transparent, smooth, and approximately 0.8-1.5 mm in diameter, after being cultured for 48 h on marine agar 2216. Based on the result of phylogenetic analysis of 16S rRNA gene sequence, strain DM8 had close relationship with Oceanisphaera profunda SM1222 (96.9%) and the type strain DSM 15406 of the type species Oceanisphaera litoralis (94.7%), respectively. Genome sequencing revealed a genome size of 3,109,059 bp and a G + C content of 46.9 mol%. It had Q-8 as the sole respiratory quinone and possessed C, summed features 3 (Cω7c/Cω6c) and summed features 8 (Cω7c/Cω6c) as major fatty acids. The major polar lipid profile was composed of phosphatidylglycerol and phosphatidylethanolamine. Based on the phenotypic, chemotaxonomic characterizations, phylogenetic properties and genome analysis, strain DM8 should represent a novel species of the genus Oceanisphaera, for which the name Oceanisphaera pacifica sp. nov. is proposed. The type strain is DM8 (= KCTC 82764 = MCCC 1K06133).
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http://dx.doi.org/10.1007/s00203-022-02928-4DOI Listing
May 2022

The Novel Amidase PcnH Initiates the Degradation of Phenazine-1-Carboxamide in Sphingomonas histidinilytica DS-9.

Appl Environ Microbiol 2022 May 17:e0054322. Epub 2022 May 17.

Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural Universitygrid.27871.3b, Nanjing, Jiangsu, People's Republic of China.

Phenazines are an important class of secondary metabolites and are primarily named for their heterocyclic phenazine cores, including phenazine-1-carboxylic acid (PCA) and its derivatives, such as phenazine-1-carboxamide (PCN) and pyocyanin (PYO). Although several genes involved in the degradation of PCA and PYO have been reported so far, the genetic foundations of PCN degradation remain unknown. In this study, a PCN-degrading bacterial strain, Sphingomonas histidinilytica DS-9, was isolated. The gene , encoding a novel amidase responsible for the initial step of PCN degradation, was cloned by genome comparison and subsequent experimental validation. PcnH catalyzed the hydrolysis of the amide bond of PCN to produce PCA, which shared low identity (only 26 to 33%) with reported amidases. The and values of PcnH for PCN were 33.22 ± 5.70 μM and 18.71 ± 0.52 s, respectively. PcnH has an Asp-Lys-Cys motif, which is conserved among amidases of the isochorismate hydrolase-like (IHL) superfamily. The replacement of Asp37, Lys128, and Cys163 with alanine in PcnH led to the complete loss of enzymatic activity. Furthermore, the genes and were found to encode PCA 1,2-dioxygenase and 1,2-dihydroxyphenazine (2OHPC) dioxygenase, which were responsible for the subsequent degradation steps of PCN. The PCN-degradative genes were highly conserved in some bacteria of the genus , with slight variations in the sequence identities. Phenazines have been widely acknowledged as a natural antibiotic for more than 150 years, but their degradation mechanisms are still not completely elucidated. Compared with the studies on the degradation mechanism of PCA and PYO, little is known regarding PCN degradation by far. Previous studies have speculated that its initial degradation step may be catalyzed by an amidase, but no further studies have been conducted. This study identified a novel amidase, PcnH, that catalyzed the hydrolysis of PCN to PCA. In addition, the PCA 1,2-dioxygenase PcaA1A2A3A4 and 2OHPC dioxygenase PcnD were also found to be involved in the subsequent degradation steps of PCN in DS-9. And the genes responsible for PCN catabolism are highly conserved in some strains of . These results deepen our understanding of the PCN degradation mechanism.
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http://dx.doi.org/10.1128/aem.00543-22DOI Listing
May 2022

Research on prediction of daily admissions of respiratory diseases with comorbid diabetes in Beijing based on long short-term memory recurrent neural network.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Feb;51(1):1-9

1. School of Public Health, Capital Medical University, Beijing 100069, China.

To compare the performance of generalized additive model (GAM) and long short-term memory recurrent neural network (LSTM-RNN) on the prediction of daily admissions of respiratory diseases with comorbid diabetes. Daily data on air pollutants, meteorological factors and hospital admissions for respiratory diseases from Jan 1st, 2014 to Dec 31st, 2019 in Beijing were collected. LSTM-RNN was used to predict the daily admissions of respiratory diseases with comorbid diabetes, and the results were compared with those of GAM. The evaluation indexes were calculated by five-fold cross validation. Compared with the GAM, the prediction errors of LSTM-RNN were significantly lower [root mean squared error (RMSE): 21.21±3.30 vs. 46.13±7.60, <0.01; mean absolute error (MAE): 14.64±1.99 vs. 36.08±6.20, <0.01], and the value was significantly higher (0.79±0.06 vs. 0.57±0.12, <0.01). In gender stratification, RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting female admission (all <0.05), but there were no significant difference in predicting male admission between two models (all >0.05). In seasonal stratification, RMSE and MAE of LSTM-RNN were lower than those of GAM in predicting warm season admission (all <0.05), but there was no significant difference in value (>0.05). There were no significant difference in RMSE, MAE and between the two models in predicting cold season admission (all >0.05). In the stratification of functional areas, the RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting core area admission (all <0.05). has lower prediction errors and better fitting than the GAM, which can provide scientific basis for precise allocation of medical resources in polluted weather in advance.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109758PMC
February 2022

Development and Preliminary Application of a Triplex Real-Time Quantitative PCR Assay for the Simultaneous Detection of , , and .

Front Microbiol 2022 28;13:888529. Epub 2022 Apr 28.

Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

Background: The protozoan parasites including , , and can infect the human intestinal tract and cause serious diseases. In this study, we aimed to develop a triplex real-time quantitative PCR (qPCR) for the simultaneous differential detection of these three intestinal protozoa.

Methods: Specific primers and TaqMan probes were designed for the 16S-like SSU rRNA sequence of , the gdh sequence of , and the 18srRNA sequence of . A triplex qPCR assay was developed based on single-duplicate experiments to evaluate its limit of detection (LOD), specificity, stability, and reproducibility. Additionally, 163 fecal samples from patients with diarrhea who tested positive for copro-antigen were tested to verify the practicality of the assay.

Results: The triplex qPCR assay could specifically detect , , and without cross-reactivity amongst the target-specific TaqMan probes of these three intestinal protozoan parasites and did not produce amplification curves for any other non-target species, and had good specificity. Amplification of serial dilutions showed that the triplex qPCR detected as little as 500 copies/μL of standard plasmid DNA. The standard curve displayed good linearity between 5 × 10 and 5 × 10 copies/μL; qPCR assays were performed with an efficiency of more than 95% and values were greater than 0.99. The triplex qPCR assay had good repeatability with intra- and inter-assay coefficients of variation less than 1.92%. Among the 163 fecal samples, four samples were confirmed to be positive for using the triplex qPCR assay.

Conclusion: The triplex qPCR established in this study not only provides a rapid, sensitive, specific tool for the simultaneous detection of , , and , but also has good practical application value.
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http://dx.doi.org/10.3389/fmicb.2022.888529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097023PMC
April 2022

Effect of berberine on copper and zinc levels in chickens infected with Eimeria tenella.

Mol Biochem Parasitol 2022 May 10;249:111478. Epub 2022 May 10.

Key Lab of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 Renmin Road, Shanghai 201620, China.

Berberine, a traditional Chinese medicine, was found to exhibit anticoccidial activity. However, its mechanism is unclear. Trace metals such as copper and zinc are extremely low (less than 0.01% of the total weight of the body) but play a vital role in organisms. In the present study, we investigated the effect of berberine on copper and zinc levels in chickens infected with Eimeria tenella. Firstly, our data confirmed that infected chickens with E. tenella exhibited classic impairment on the 8th day of post infection, such as weight loss and increased feed conversion. Further study showed that E. tenella infection decreased the contents of copper and zinc in the liver and serum of chickens. Berberine was similar to amprolium and significantly improved the pathogenic conditions. Berberine could restore copper and zinc imbalance caused by E. tenella in chickens to a large extent. Studies on the development of cecum lesions demonstrated that the protective effect of berberine on the intestinal cecum was similar to that of the Cu/Zn mixture. Additionally, the mRNA expression of several metal transport related genes of the chick small intestine, including zinc transporter 1, copper transporter 1 and divalent metal ion transporter 1, was elevated by the treatment with berberine. Taken together, we speculate that the anticoccidial activity of berberine may be related to the maintenance of certain metals (Cu/Zn) homeostasis by affecting mRNA expression of their transport genes. However, the mode of action of BBR on these vital metals in the chicks infected with E. tenella still needs to be further studied.
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http://dx.doi.org/10.1016/j.molbiopara.2022.111478DOI Listing
May 2022

IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia.

Nat Cancer 2022 May 9;3(5):595-613. Epub 2022 May 9.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Acute myeloid leukemia (AML) remains difficult to treat and requires new therapeutic approaches. Potent inhibitors of the chromatin-associated protein MENIN have recently entered human clinical trials, opening new therapeutic opportunities for some genetic subtypes of this disease. Using genome-scale functional genetic screens, we identified IKAROS (encoded by IKZF1) as an essential transcription factor in KMT2A (MLL1)-rearranged (MLL-r) AML that maintains leukemogenic gene expression while also repressing pathways for tumor suppression, immune regulation and cellular differentiation. Furthermore, IKAROS displays an unexpected functional cooperativity and extensive chromatin co-occupancy with mixed lineage leukemia (MLL)1-MENIN and the regulator MEIS1 and an extensive hematopoietic transcriptional complex involving homeobox (HOX)A10, MEIS1 and IKAROS. This dependency could be therapeutically exploited by inducing IKAROS protein degradation with immunomodulatory imide drugs (IMiDs). Finally, we demonstrate that combined IKAROS degradation and MENIN inhibition effectively disrupts leukemogenic transcriptional networks, resulting in synergistic killing of leukemia cells and providing a paradigm for improved drug targeting of transcription and an opportunity for rapid clinical translation.
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http://dx.doi.org/10.1038/s43018-022-00366-1DOI Listing
May 2022

Chemical synthesis of polysaccharides.

Curr Opin Chem Biol 2022 May 5;69:102154. Epub 2022 May 5.

Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China; School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China. Electronic address:

Here we summarize the chemical syntheses of glycans containing over 20 monosaccharide units, with the recent syntheses of ultra-long glycans, including a 92mer arabinogalactan, a 100mer and a 151mer mannan, and a 128mer rhamnomannan, being highlighted. The assembly strategies, glycosylation methods, and protecting group manipulations, which are crucial to the successful synthesis, are discussed to give guidance for the future synthesis of various polysaccharides.
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http://dx.doi.org/10.1016/j.cbpa.2022.102154DOI Listing
May 2022

Aggregation-Induced Luminescence Based UiO-66: Highly Selective Fast-Response Styrene Detection.

ACS Appl Mater Interfaces 2022 May 4;14(19):22510-22520. Epub 2022 May 4.

Department of Materials Science and Engineering, National University of Singapore, 117574, Singapore.

One of the main pollutants in indoor air is volatile organic compounds (VOCs), which can cause great harm to human health. So the development of a VOC detection technology is of great significance. In this work, a tetraphenylethylene-functionalized UiO-66 based on aggregation-induced emission was successfully prepared. The UiO-66-TBPE structure exhibits the characteristic blue emission of TBPE ligands under UV excitation and can be used as a luminescence sensor for fast and efficient detection of VOCs. More importantly, UiO-66-TBPE has a high fluorescence sensing selectivity in -xylene and styrene vapor. To further improve the practical performance, we combined UiO-66-TBPE with the polymer polyacrylate (PA) to obtain a flexible hybrid membrane with fast detection performance for styrene vapor within the 30 s. The deeper sensing mechanism of -xylene and styrene inducing different fluorescence enhancement and fluorescence quenching is explained by a combination of modern characterization techniques and computer simulation. Finally, we applied UiO-66-TBPE/PA to leather and still maintained a good sensing performance. It provides a potential way for the application of fluorescent metal-organic frameworks (MOFs) to detect VOCs in daily life.
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http://dx.doi.org/10.1021/acsami.2c06880DOI Listing
May 2022

The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction.

Reprod Biol Endocrinol 2022 Apr 29;20(1):73. Epub 2022 Apr 29.

Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China.

Background: Normal motor activity of the fallopian tube is critical for human reproduction, and abnormal tubal activity may lead to ectopic pregnancy (EP) or infertility. Progesterone has an inhibitory effect on tubal contraction; however, the underlying mechanisms remain unclear. Small-conductance calcium-activated K channel 3 (SK3) is abundantly expressed in platelet-derived growth factor receptor α positive (PDGFRα+) cells and was reported to be important for the relaxation of smooth muscle. The present study aims to explore the expression of SK3 in the human fallopian tube and its role in progesterone-induced inhibition of tubal contraction.

Methods: We collected specimens of fallopian tubes from patients treated by salpingectomy for EP (EP group) and other benign gynecological diseases (Non-EP group). The expression of SK3 was detected by quantitative real-time polymerase chain reaction, western blot, immunocytochemistry, and immunohistochemistry analyses. Isometric tension experiments were performed to investigate the role of SK3 in progesterone-induced inhibition of tubal contraction.

Results: The baseline amplitude and frequency of human fallopian tube contraction were both statistically lower in the EP group compared with the non-EP group. The expression levels of SK3 in different portions of fallopian tubes from the non-EP group were significantly higher than in those from the EP group. Progesterone had an inhibitory effect on tubal contraction, mainly on the amplitude, in both groups, and SK3 as well as other calcium-activated K channels may be involved. SK3-expressing PDGFRα (+) cells were detected in the human fallopian tube.

Conclusions: The expression of SK3 is lower in the EP group, and SK3 is involved in the progesterone-induced inhibition of human fallopian tube contraction.
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http://dx.doi.org/10.1186/s12958-022-00932-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052544PMC
April 2022

Restored CD8PD-1 T Cells Facilitate the Response to Anti-PD-1 for Patients With Pancreatic Ductal Adenocarcinoma.

Front Oncol 2022 11;12:837560. Epub 2022 Apr 11.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Purpose: We aimed to investigate the restoration of CD8PD-1 T cells through adoptive T-cell therapy (ACT) in relation to the prognosis and the therapeutic response to anti-PD-1 in patients with advanced pancreatic cancer (APC).

Methods: A total of 177 adult patients who underwent tumor resection as initial treatment for pancreatic ductal adenocarcinoma (PDAC) from February 2013 to July 2019 at Zhongnan Hospital of Wuhan University were enrolled in this study. Another cohort of 32 patients with APC was prospectively enrolled from Capital Medical University Cancer Center between June 1, 2013, and May 30, 2019.

Results: Of the 177 patients who received tumor resection, 67 tumor samples showed overexpression of PD-L1 and 110 patients with low expression of PD-L1. We found that overexpressed PD-L1 was a significant prognostic factor related to overall survival (OS). Furthermore, we tested the percentage of peripheral CD8PD-1 T cells in all patients and found that it was significantly correlated with the PD-L1 expression and the prognosis of patients with PDAC. The peripheral blood T lymphocyte subtypes were tracked for 30 months, and CD8PD-1 cells were shown to decrease. After that, we performed ACT for patients with APC in another cancer center. We found that the ratios of posttreatment of ACT/pre-ACT CD8PD-1 T cells were significantly related to the prognosis of patients with APC. Moreover, patients with combined treatment of ACT with anti-PD-1 had significantly favorable OS.

Conclusions: This study showed that the CD8PD-1 T-cell level was related to the expression of PD-L1. Restoring CD8PD-1 T cells in patients with APC by treatment of ACT significantly benefits the prognosis and facilitates the response to anti-PD-1.
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http://dx.doi.org/10.3389/fonc.2022.837560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035626PMC
April 2022

Highly efficient adsorption of chromium on N, S-codoped porous carbon materials derived from paper sludge.

Sci Total Environ 2022 Apr 16;834:155312. Epub 2022 Apr 16.

State Key Laboratory of Pulp and Paper Engineering, School of Light Industry and Engineering, South China University of Technology, Guangzhou, China; School of Environment and Energy, Guangdong Provincial Key Laboratory of Solid Wastes Pollution Control and Recycling South China University of Technology, Guangzhou, Guangdong 510006, China.

The synergistic effect of heteroatoms is a viable method to enhance the adsorption performance of heavy metal onto carbon-based materials. However, the high cost, complex operation and a lot of pollution from the synthesis process have limited its development. Herein, a facile two-step pyrolysis method is used to prepare in situ N and S doped porous biochar from paper mill sludge for the removal of Cr(VI) from aqueous environment. The NSC-450 sample prepared under the optimum conditions has a large specific surface area of 3336.7 m g, an average pore size of 2.56 nm and a total pore volume of 2.10 cm g, manifesting the excellent adsorption capacity of 356.25 mg g for Cr(VI). The adsorption of Cr(VI) by NSC-450 is consistent with the Langmuir isotherm and pseudo-second-order model, suggesting a spontaneous and endothermic chemisorption process. The analysis results show that the NH, graphitic nitrogen and thiophene structures have a positive effect on converting a large amount of Cr(VI) to Cr(III) by synergistic reduction, indicating obviously facilitating Cr(VI) removal compared to other sites. Therefore, in this material, the strong adsorption mechanism is mainly reductive complexation. Moreover, the effects of real water quality, anions, cations and fulvic acid on the adsorption behavior of Cr(VI) onto the NSC-450 were further investigated. The results demonstrate that the chromium removal rate remains above 82% even in actual electroplating wastewater, suggesting NSC-450 has great practical application prospect. This work offered a feasible method for high-value utilization of sludge, but also provided a novel perspective for the future design of heteroatom-doped carbon materials for promoting to eliminate hexavalent chromium from water environment.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155312DOI Listing
April 2022

Out-of-pocket medical expenditure and associated factors of advanced colorectal cancer in China: a multi-center cross-sectional study.

Ann Transl Med 2022 Mar;10(6):356

Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, China.

Background: Colorectal cancer (CRC) causes a substantial disease burden in China. Information on the medical expenditure of CRC patients is critical for decision-makers to allocate medical resources reasonably, however, relevant data is limited in China, especially advanced CRC. The aim of this survey was to quantify the out-of-pocket medical expenditure of advanced CRC and explore associated factors.

Methods: A nation-wide, multi-center, cross-sectional survey was conducted from March 2020 to March 2021. Nineteen hospitals in seven geographical regions were selected by multi-stage stratified sampling. For each eligible CRC patient with stage III or IV disease in the selected hospitals, the socio-demographics, clinical information, and range of out-of-pocket medical expenditure data were collected based on patients' self-reporting or medical records. Multivariable logistic analysis was used to explore associated factors of medical expenditure. All statistical analyses were conducted using SAS 9.4.

Results: The mean age of the 4,428 advanced CRC patients included was 59.5±11.6 years, 59.6% were male, and 80.1% of patients were in stage III or IV at the time of diagnosis. Besides, 57.2% of patients had an annual household income of less than 50,000 Chinese Yuan (CNY), 40.9% of patients had an out-of-pocket medical expenditure of 50,000-99,999 CNY. As for the affordability of medical expenditure, 33.2% could afford 50,000-99,999 CNY. Multivariate analysis showed that patients who were in the southern [odds ratio (OR): 1.63, 95% confidence interval (CI): 1.31-2.03] and southwestern (OR: 1.55, 95% CI: 1.25-1.93), were in stage III at the time of diagnosis (OR: 1.33, 95% CI: 1.13-1.57), visited three or more hospitals (OR: 1.26, 95% CI: 1.04-1.52), had sought cross-regional health care (OR: 1.60, 95% CI: 1.40-1.83), used genetic testing (OR: 1.26, 95% CI: 1.10-1.45) and targeted drugs (OR: 2.12, 95% CI: 1.79-2.51) had higher out-of-pocket medical expenditure.

Conclusions: Patients with advanced CRC had a high out-of-pocket medical expenditure. It is necessary to strengthen the prevention and control of CRC to reduce the disease burden; also, it is critical to deepen the reform of the medical system, increase proportion of medical insurance reimbursement, and remove barriers to cross-regional health care.
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http://dx.doi.org/10.21037/atm-22-1001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011322PMC
March 2022

Health-related quality of life in advanced colorectal cancer patients in China: a nationwide hospital-based survey.

Ann Transl Med 2022 Mar;10(6):328

Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Colorectal cancer (CRC) is one of the most common cancers in China, and most CRC patients have already reached an advanced stage by the time of initial diagnosis. Due to the loss of health as a result of cancer, it has consequence on the treatment which may affect the psychophysical and social impairment of CRC patients. These indicators (psychophysical, function and social impairment) affect the health-related quality of life (HRQOL). There are limited studies that focus on advanced CRC patients in China. This study aimed to assess the HRQOL and its associated factors of advanced CRC patients in China.

Methods: This was a cross-sectional, nationwide, hospital-based, and multi-center survey. According to the traditional administrative district definition, we selected 19 hospitals in 7 regions by multi-stage stratified sampling in China. For each eligible CRC patient with stage III or IV in the selected hospitals, socio-demographics, clinical information, and HRQOL were collected based on patients' self-reporting and/or medical records between March 2020 and March 2021. Patients completed the Functional Assessment of Cancer Therapy Colorectal (FACT-C) plus-traditional Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-9.

Results: A total of 4,589 CRC patients (mean age 60.1 years, including 2,730 males and 1,859 females) were included. The total score of HRQOL in population was 128.2±24.70. There were significant differences in the overall score of HRQOL in gender, education level, occupation, region, disease type, and disease stage (P<0.05). The score of HRQOL was better in males, undergraduates and above, unemployed/laid-off, and southwestern and central China. Multivariate analysis showed that education level, occupation, location, number of hospitals visited and treatment methods, and gender were associated with utilities of CRC patients.

Conclusions: The HRQOL is an important outcome measure for CRC patients. The HRQOL scores differed according to socio-demographic and clinical characteristics, and findings of these factors were associated with education level, occupation, region, number of visited and treatment methods, and gender.
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http://dx.doi.org/10.21037/atm-22-991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011208PMC
March 2022

Status and associated factors of cross-regional healthcare-seeking among patients with advanced colorectal cancer in China: a multicenter cross-sectional study.

Ann Transl Med 2022 Mar;10(6):342

Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, China.

Background: The imbalanced allocation of medical resources leads to the occurrence of cross-regional healthcare-seeking in China. Due to the low cure rate, advanced colorectal cancer (CRC) patients may seek cross-regional healthcare for high-level medical facilities. Investigating status of cross-regional healthcare-seeking and its associated factors among advanced CRC patients is important for policymakers to understand access to health services and improve the quality of oncology services.

Methods: From March 2020 to March 2021, a cross‑sectional, nation-wide, hospital-based, multi-center survey was conducted. Nineteen hospitals in seven regions were selected by multi-stage stratified sampling. All eligible CRC patients in the selected hospitals were invited to participate in the current study. The outcome variable, cross-regional healthcare-seeking, was defined as seeking health facilities outside the local administration policy of medical insurance. The demographics, clinical information, and medical treatment history of each eligible CRC patient in stage III or IV, were collected through the patients' self-reporting or medical records by trained interviewers. Univariate and multivariate logistic analyses were used to explore the associated factors of cross-regional healthcare-seeking. All statistical analyses were conducted using SAS 9.4.

Results: A total of 4,589 individuals with advanced CRC were included. The average age of the patients was 60.1±11.6 years, and 59.5% were males. About 37.5% of the patients suffered from metastatic CRC at first diagnosis. Approximately 36.5% of the patients had sought cross-regional health care previously, and among them, 31.9% had encountered problems. The most common problems included complicated procedures (95.3%), unreimbursed expenses of outpatient service (71.0%), and reimbursement delay (59.4%). Logistic regression analysis showed that patients who completed undergraduate or above [odds ratio (OR) =1.40, 95% confidence interval (CI): 1.13-1.73], had an annual household income of more than 100,000 Chinse Yuan (CNY) (OR =1.46, 95% CI: 1.21-1.78), and had metastasis at diagnosis (OR =1.33, 95% CI: 1.18-1.51) were more likely to seek cross-regional health care.

Conclusions: About one third of advanced CRC patients seek cross-regional health care, and 31.9% had encountered problems. There is a need to simplify procedures of reimbursement, optimize direct settlement system and referral mechanisms in order to improve the equality of health services.
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http://dx.doi.org/10.21037/atm-22-1003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011287PMC
March 2022

Efficacy and toxicity of SEAM (semustine, etoposide, cytarabine, and melphalan) conditioning regimen followed by autologous stem cell transplantation in lymphoma.

Hematology 2022 Dec;27(1):404-411

First Affiliated Hospital of Soochow University, Department of Hematology, Suzhou, Jiangsu, People's Republic of China.

Objectives: The aim of this retrospective study was to evaluate the safety and efficacy of SEAM regimen followed by auto-SCT in lymphoma.

Patients And Methods: We retrospectively reviewed the records of patients with lymphoma who underwent auto-SCT with SEAM conditioning regimen from January 2010 to June 2018 at our centre. In total, 97 patients were analysed.

Results: The median time to neutrophil engraftment and platelet engraftment was 9.5 days (range, 7-15 days) and 12 days (range, 7-25 days), respectively. Grade 3-4 nausea/vomiting, mucositis and diarrhoea were observed in 21.6%, 36.1%, and 11.3% of patients, respectively. Treatment-related mortality at 100 days occurred in 2 patients (2.1%). After a median follow-up time of 53.9 months, the 3-year incidence of disease relapse or progression was 34%. The estimated progression-free survival and overall survival at 3 years were 62% and 75%, respectively. Compared with previous studies using BEAM as the conditioning regimen, this study shows that the SEAM regimen has a comparable efficacy and safety profile.

Conclusions: The SEAM regimen is feasible and might be an ideal alternative to BEAM regimen for lymphoma auto-SCT.
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http://dx.doi.org/10.1080/16078454.2022.2051864DOI Listing
December 2022

Co/Co-N/Co-O Rooted on rGO Hybrid BCN Nanotube Arrays as Efficient Oxygen Electrocatalyst for Zn-Air Batteries.

ACS Appl Mater Interfaces 2022 Apr 11;14(15):17249-17258. Epub 2022 Apr 11.

Jiangxi Provincial Key Laboratory for Simulation and Modelling of Particulate Systems, International Institute for Innovation, Jiangxi University of Science and Technology, Nanchang 330013, China.

Developing high-performance non-noble metal bifunctional oxygen reduction and evolution reaction electrocatalysts is a critical factor for the commercialization of rechargeable Zn-air batteries. Herein, Co/Co-N/Co-O rooted on reduced graphene oxide (rGO) hybrid boron and nitrogen codoped carbon (BCN) nanotube arrays (BCN/rGO-Co) is prepared by facile low-temperature precross-linking and high-temperature pyrolysis treatment. Benefit from the synergistic effect of its B/N codoping, Co/Co-N/Co-O bifunctional active sites, 3D hybrid porous structure of BCN nanotubes, and highly conductive rGO sheets. The obtained BCN/rGO-Co exhibits superior bifunctional oxygen catalytic activity with a positive ORR half-wave potential (0.85 V) and a low OER potential (1.61 V) at 10 mA cm. Additionally, the BCN/rGO-Co-based liquid Zn-air batteries displays a large peak power density of 157 mW cm, and a long charge/discharge cycle stability of 200 h, outdoing the commercial Pt/C+Ru/C catalyst.
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http://dx.doi.org/10.1021/acsami.2c00163DOI Listing
April 2022

Preoperative Prediction of Central Cervical Lymph Node Metastasis in Fine-Needle Aspiration Reporting Suspicious Papillary Thyroid Cancer or Papillary Thyroid Cancer Without Lateral Neck Metastasis.

Front Oncol 2022 23;12:712723. Epub 2022 Mar 23.

Department of Medical Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: No non-invasive method can accurately determine the presence of central cervical lymph node (CCLN) metastasis in papillary thyroid cancer (PTC) until now. This study aimed to investigate factors significantly associated with CCLN metastasis and then develop a model to preoperatively predict CCLN metastasis in fine-needle aspiration (FNA) reporting suspicious papillary thyroid cancer (PTC) or PTC without lateral neck metastasis.

Patients And Methods: Consecutive inpatients who were diagnosed as suspicious PTC or PTC in FNA and underwent partial or total thyroidectomy and CCLN dissection between May 1, 2016 and June 30, 2018 were included. The total eligible patients were randomly divided into a training set and an internal validation set with the ratio of 7:3. Univariate analysis and multivariate analysis were conducted in the training set to investigate factors associated with CCLN metastasis. The predicting model was built with factors significantly correlated with CCLN metastasis and validated in the validation set.

Results: A total of 770 patients were eligible in this study. Among them, 268 patients had histologically confirmed CCLN metastasis, while the remaining patients did not. Factors including age, mutation, multifocality, size, and capsule involvement were found to be significantly correlated with the CCLN metastasis in univariate and multivariate analysis. A model used to predict the presence CCLN metastasis based on these factors and US CCLN status yielded AUC, sensitivity, specificity and accuracy of 0.933 (95%CI: 0.905-0.960, p < 0.001), 0.816, 0.966 and 0.914 in the training set and 0.967 (95%CI: 0.943-0.991, p < 0.001), 0.897, 0.959 and 0.936 in the internal validation set.

Conclusion: Age, mutation, multifocality, size, and capsule involvement were independent predictors of CCLN metastasis in FNA reporting suspicious PTC or PTC without lateral neck metastasis. A simple model was successfully built and showed excellent discrimination to distinguish patients with or without CCLN metastasis.
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http://dx.doi.org/10.3389/fonc.2022.712723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983925PMC
March 2022

Maternal probiotics supplementation improves immune and antioxidant function in suckling piglets via modifying gut microbiota.

J Appl Microbiol 2022 Apr 9. Epub 2022 Apr 9.

Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.

Aim: Probiotics could improve the health, growth, and development of host or their foetuses/offspring via regulating gut microbiota. The present study was conducted to determine the effects of maternal probiotics supplementation on gut microbiota and metabolites of sows and their suckling piglets, as well as plasma biochemical parameters, oxidative/anti-oxidative indexes, and inflammatory cytokine levels of suckling piglets.

Methods And Results: A total of 32 pregnant Bama mini-pigs were selected and randomly divided into two groups. The sows were fed a basal diet (control group) or a basal diet supplemented with probiotics (probiotics group) from mating to day 21 of lactation. Samples from sows were collected on day 105 of pregnancy and day 21 of lactation and from piglets on day 21 of lactation. The results showed that probiotics supplementation increased the faecal abundances of Ruminococcus, Bacteroides, and Anaeroplasma and decreased Tenericutes on day 105 of pregnancy while increased the abundances of Actinobacteria and Anaerostipes and decreased Proteobacteria and Desulfovibrio on day 21 of lactation. In addition, probiotics supplementation decreased the faecal levels of tryptamine, putrescine, and cadaverine on day 105 of pregnancy and isovalerate and skatole on day 21 of lactation while increased butyrate level on day 21 of lactation. Further studies showed that maternal probiotics supplementation decreased the plasma levels of AMM, TC, LDL-C, Ala, Tau, MDA, H O , IL-1β, IL-2, IL-6, and IFN-α of suckling piglets. Moreover, maternal probiotics supplementation increased the abundances of Deferribacteres, Fusobacteria, and Fusobacterium while decreased Anaerostipes in piglet's colon. Spearman's correlation analysis revealed a potential link between gut microbiota alterations and their metabolites.

Conclusions: Dietary probiotics supplementation during pregnancy and lactation periods could improve sow status, alleviate oxidative stress and inflammation response, and improve nutrient metabolism of piglets by altering the gut microbiota.

Significance And Impact Of The Study: The probiotics alter maternal and offspring's gut microbiota involving in offspring's physiological and metabolic changes, and present a new perspective that the effects of gut microbiota changes induced by probiotics supplementation will help in addressing the growth and development and health problem of their foetuses/offspring.
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http://dx.doi.org/10.1111/jam.15572DOI Listing
April 2022

Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis.

Cell Rep 2022 04;39(1):110587

Department of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA; Stem Cell Transplantation Program, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address:

Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7's control of hematopoietic maturation. We find that juvenile Cbx2 hematopoietic tissues show impairment of B-lymphopoiesis, a precocious adult-like myeloid bias, and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a mechanism of regulation of HSPC output via chromatin modification as a function of age with potential impact on age-biased pediatric and adult blood disorders.
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http://dx.doi.org/10.1016/j.celrep.2022.110587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029260PMC
April 2022

Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease.

Front Immunol 2022 8;13:829425. Epub 2022 Mar 8.

School of Medicine, South China University of Technology, Guangzhou, China.

Background: Systemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation.

Methods: Widely targeted plasma metabolomic and lipidomic profiling was performed in 1,234 patients with CAD. Laboratory circulating inflammatory markers were mainly used to define general systemic immune and low-grade inflammatory states. Multivariable-adjusted linear regression was adopted to assess the associations between 860 metabolites and 7 inflammatory markers. Least absolute shrinkage and selection operator (LASSO) logistic-based classifiers and multivariable logistic regression were applied to identify biomarkers of inflammatory states and develop models for discriminating an advanced inflammatory state.

Results: Multiple metabolites and lipid species were linearly associated with the seven inflammatory markers [false discovery rate (FDR) <0.05]. LASSO and multivariable-adjusted logistic regression analysis identified significant associations between 45 metabolites and systemic immune-inflammation index, 46 metabolites and neutrophil-lymphocyte ratio states, 32 metabolites and low-grade inflammation score, and 26 metabolites and high-sensitivity C-reactive protein states ( < 0.05). Glycerophospholipid metabolism and arginine and proline metabolism were determined as key altered metabolic pathways for systemic immune and low-grade inflammatory states. Predictive models based solely on metabolite combinations showed feasibility (area under the curve: 0.81 to 0.88) for discriminating the four parameters that represent inflammatory states and were successfully validated using a validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, was related to carotid and coronary arteriosclerosis indicators ( < 0.05).

Conclusions: This study provides further information on the relationship between plasma metabolite profiles and inflammatory states represented by various inflammatory markers in CAD. These metabolic markers provide potential insights into pathological changes during CAD progression and may aid in the development of therapeutic targets.
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http://dx.doi.org/10.3389/fimmu.2022.829425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965586PMC
March 2022

Analysis of Mononuclear Phagocytes Disclosed the Establishment Processes of Two Macrophage Subsets in the Adult Murine Kidney.

Front Immunol 2022 10;13:805420. Epub 2022 Mar 10.

Department of Physiology and Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The interstitium of kidney involves a variety of components including resident immune cells, in particular mononuclear phagocytes. However, many proposed markers for distinguishing macrophages or dendritic cells are, in fact, shared by the majority of renal mononuclear phagocytes, which impedes the research of kidney diseases. Here, by employing a flow cytometry strategy and techniques of fate mapping, imaging and lineage depletion, we were able to demarcate renal monocytes, macrophages and dendritic cells and their subsets in mice. In particular, using this strategy, we found that even in steady state, the renal macrophage pool was continuously replenished by bone marrow-derived monocytes in a stepwise process, i.e., from infiltration of classical monocyte, to development of nonclassical monocyte and eventually to differentiation to macrophages. In mechanism, we demonstrated that the ligation of tissue-anchored CX3CL1 and monocytic CX3CR1 was required for promoting monocyte differentiation to macrophages in the kidney, but CX3CL1-CX3CR1 signaling was dispensable in monocyte infiltrating into the kidney. In addition to the bone marrow-derived macrophages, fate mapping in adult mice revealed another population of renal resident macrophages which were embryo-derived and self-maintaining. Thus, the dissecting strategies developed by us would assist in exploration of the biology of renal mononuclear phagocytes.
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http://dx.doi.org/10.3389/fimmu.2022.805420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960422PMC
April 2022

CdS-Based Catalysts Derived from TMeQ[6]/[CdCl]-Based Frameworks for Oxidation Benzylamine.

Inorg Chem 2022 Apr 31;61(14):5607-5615. Epub 2022 Mar 31.

Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, People's Republic of China.

The anion-induced outer surface interaction of Q[]s is an important driving force in the construction of Q[]-based supramolecular frameworks. In this work, a symmetric tetramethyl-substituted cucurbit[6]uril (TMeQ[6]) is selected as the basic structural block. Using the anion-induced outer surface interaction of Q[]s derived from [CdCl] anions formed by Cd cations in a HCl medium, four different TMeQ[6]-[CdCl]-based supramolecular frameworks are constructed. Three of the most common TMeQ[6]-[CdCl]-based supramolecular frameworks are selected for further vulcanization, and three different CdS/TMeQ[6]-based framework catalysts with different structures and properties are obtained. The catalytic activities of these three CdS/TMeQ[6]-based framework catalysts are investigated by the coupling photocatalytic reaction of aminobenzyl, and the results showed that the catalytic activities of the three catalysts are all higher than that of pure CdS. Therefore, this work establishes that it is possible to establish a method for synthesizing the Q[]-based framework-supported catalysts by first synthesizing TMeQ[6]-[CdCl]-based supramolecular frameworks and then forming Q[]-based framework supported catalysts by sulfurization or reduction.
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http://dx.doi.org/10.1021/acs.inorgchem.2c00096DOI Listing
April 2022

A Novel Immune-Related Prognostic Signature Predicting Survival in Patients with Pancreatic Adenocarcinoma.

J Oncol 2022 18;2022:8909631. Epub 2022 Mar 18.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Pancreatic adenocarcinoma (PAAD) carries the lowest survival rate of all major organ cancers, which is of dismal prognosis and high mortality rate. Thus, the present study attempted to identify a few novel prognostic biomarkers and establish an immune-related prognostic signature which could predict the prognosis of PAAD. Four prognostic immune-related genes (IRGs) including S100A6, S100A10, S100A16, and SDC1 were screened by differentially expressed gene (DEG) identification and weighted gene coexpression network analysis (WGCNA). Subsequent analysis proved the high expression of these IRGs in PAAD tissues, suggested by TCGA-PAAD data, merged microarray-acquired dataset (MMD), GEPIA, and Oncomine webtool. By using MMD and TCGA-PAAD data, S100A6 (MMD: AUC = 0.897; TCGA: AUC = 0.843), S100A10 (MMD: AUC = 0.880; TCGA: AUC = 0.780), S100A16 (MMD: AUC = 0.878; TCGA: AUC = 0.838), and SDC1 (MMD: AUC = 0.885; TCGA: AUC = 0.812) exhibited excellent diagnostic efficiency for PAAD. By conducting connectivity map (CMap) analysis, we concluded that three molecule drugs (sulpiride, famotidine, and nalidixic acid) might have worked in the treatment of PAAD. Then, an immune-related prognostic index was constructed, which was validated as an independent prognostic factor for PAAD patients (=0.004). We further constructed a nomogram by using this immune-related signature and age, the prognostic value of which was validated by using concordance index (C-index = 0.780) and area under curve (AUC = 0.909). Moreover, the immune-related prognostic signature was associated with response to anti-PD-1/L1 immunotherapy. To sum up, four IRGs were screened out and verified to be novel immune-related prognostic biomarkers in PAAD. Besides, sulpiride, famotidine, and nalidixic acid might be potential choices in the treatment of PAAD. An immune-related signature was established to show great potential for prognosis prediction for PAAD, independently, which might guide more effective immunotherapy strategies. A nomogram is further established by using this immune-related prognostic index, which might contribute to more effective prognosis prediction in PAAD patients.
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http://dx.doi.org/10.1155/2022/8909631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956421PMC
March 2022

sp. nov. and sp. nov., two novel isolated from the marine sediment.

Int J Syst Evol Microbiol 2022 Mar;72(3)

Marine College, Shandong University, Weihai, Shandong 264209, PR China.

Two novel, designated strains 29W222 and 2943, were isolated from the marine sediment from Aoshan Bay, Jimo, PR China. Growth was observed at pH 6.0-8.5 (optimum, pH 7.5) for strain 29W222, and pH 5.5-8.5 (pH 7.0) for strain 2943. Both strains displayed growth in 0.5-6 % NaCl with an optimum at 1 % for 29W222; 0.5 % for 2943. Both strains grew optimally at 33 °C. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that 29W222 and 2943 represented members of the genus and strain 29W222 was most closely related to KMM 6220 (97.9 % sequence similarity) and AK7 (95.0 %), and 2943 to AK7 (95.7 %) and KMM 6220 (94.8 %). The genomic DNA G+C contents of 29W222 and 2943 were 39.9 and 37.7 mol%, respectively. The results of chemotaxonomic analysis indicated that the sole respiratory quinone was menaquinone 7 (MK-7), and the major fatty acid was iso-C for both strains. Average nucleotide identity and average amino acid identity values between strain 29W222 and KMM 6220 were 78.9 and 83.6 %, respectively; the corresponding values between 2943 and AK7 were 69.8 and 63.6 %, respectively. Therefore, strains 29W222 and 2943 represent to two novel species of the genus , for which the names sp. nov. (29W222=KCTC 62848=MCCC 1K05194) and sp. nov. (2943=KCTC 62847= MCCC 1K05144) are proposed, respectively.
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http://dx.doi.org/10.1099/ijsem.0.005308DOI Listing
March 2022

A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia.

Genes Dev 2022 Mar 17;36(5-6):368-389. Epub 2022 Mar 17.

Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.

Acute myeloid leukemia with KMT2A (MLL) rearrangements is characterized by specific patterns of gene expression and enhancer architecture, implying unique core transcriptional regulatory circuitry. Here, we identified the transcription factors MEF2D and IRF8 as selective transcriptional dependencies of KMT2A-rearranged AML, where MEF2D displays partially redundant functions with its paralog, MEF2C. Rapid transcription factor degradation followed by measurements of genome-wide transcription rates and superresolution microscopy revealed that MEF2D and IRF8 form a distinct core regulatory module with a narrow direct transcriptional program that includes activation of the key oncogenes MYC, HOXA9, and BCL2. Our study illustrates a mechanism of context-specific transcriptional addiction whereby a specific AML subclass depends on a highly specialized core regulatory module to directly enforce expression of common leukemia oncogenes.
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http://dx.doi.org/10.1101/gad.349284.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973843PMC
March 2022

FSH mediates estradiol synthesis in hypoxic granulosa cells by activating glycolytic metabolism through the HIF-1α-AMPK-GLUT1 signaling pathway.

J Biol Chem 2022 Mar 15;298(5):101830. Epub 2022 Mar 15.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. Electronic address:

Owing to the avascular environment within ovarian follicles, granulosa cells (GCs) are believed to live in a hypoxic niche. Follicle-stimulating hormone (FSH)-mediated steroidogenesis is crucial for normal growth and maturation of ovarian follicles, but it remains unclear how FSH stimulates estradiol (E2) synthesis under hypoxic conditions. Here, we aimed to explore whether FSH affects the ATP production required for estrogen synthesis from the perspective of glucose metabolism. It was observed that the levels of both E2 and HIF-1α were markedly increased in a dose-dependent manner in mouse ovarian GCs after the injection of FSH in vivo, indicating that hypoxia/HIF-1α may be relevant to FSH-induced E2 synthesis. By treating hypoxic GCs with FSH in vitro, we further revealed that the activation of the AMP-activated protein kinase (AMPK)-GLUT1 pathway, which in turn stimulates ATP generation, may be essential for FSH-mediated E2 production during hypoxia. In contrast, inhibition of AMPK or GLUT1 with siRNAs/antagonist both repressed glycolysis, ATP production, and E2 synthesis despite FSH treatment. Moreover, blocking HIF-1α activity using siRNAs/PX-478 suppressed AMPK activation, GLUT1 expression, and E2 levels in FSH-treated GCs. Finally, the in vitro findings were verified in vivo, which showed markedly increased AMPK activity, GLUT1 expression, glycolytic flux, ATP levels, and E2 concentrations in ovarian GCs following FSH injection. Taken together, these findings uncovered a novel mechanism for FSH-regulating E2 synthesis in hypoxic GCs by activating glycolytic metabolism through the HIF-1α-AMPK-GLUT1 pathway.
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http://dx.doi.org/10.1016/j.jbc.2022.101830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036125PMC
March 2022

More than a Leaving Group: N-Phenyltrifluoroacetimidate as a Remote Directing Group for Highly α-Selective 1,2-cis Glycosylation.

Angew Chem Int Ed Engl 2022 May 23;61(21):e202201510. Epub 2022 Mar 23.

Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu, 211198, China.

The anomeric configuration can greatly affect the biological functions and activities of carbohydrates. Herein, we report that N-phenyltrifluoroacetimidoyl (PTFAI), a well-known leaving group for catalytic glycosylation, can act as a stereodirecting group for the challenging 1,2-cis α-glycosylation. Utilizing rapidly accessible 1,6-di-OPTFAI glycosyl donors, TMSOTf-catalyzed glycosylation occurred with excellent α-selectivity and broad substrate scope, and the remaining 6-OPTFAI group can be cleaved chemoselectively. The remote participation of 6-OPTFAI is supported by the first characterization of the crucial 1,6-bridged bicyclic oxazepinium ion intermediates by low-temperature NMR spectroscopy. These cations were found to be relatively stable and mainly responsible for the present stereoselectivities. Further application is highlighted in glycosylation reactions toward trisaccharide heparins as well as the convergent synthesis of chacotriose derivatives using a bulky 2,4-di-O-glycosylated donor.
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http://dx.doi.org/10.1002/anie.202201510DOI Listing
May 2022

A Bidirectional Relationship Between Hyperuricemia and Metabolic Dysfunction-Associated Fatty Liver Disease.

Front Endocrinol (Lausanne) 2022 16;13:821689. Epub 2022 Feb 16.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Background And Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly emerged term that is suggested to better reflect the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, the association between hyperuricemia and MAFLD has not been explored in the Chinese population. Meantime, this study also examined the temporal relationship between the two entities in a longitudinal cohort.

Methods: We conducted a retrospective cross-sectional study including 1,587,962 individuals from 19 health check-up centers in China from 2009-2017 and a longitudinal study with 16,112 individuals. A logistic regression model was applied to determine the association between hyperuricemia and MAFLD in a cross-sectional study. The Cox regression model was used to explore the association between hyperuricemia at baseline and subsequent onset of MAFLD or the association between the presence of MAFLD at baseline and the subsequent incidence of hyperuricemia. The cross-lagged analysis was applied to exam the temporal relationship between hyperuricemia and MAFLD.

Results: In the cross-sectional study, hyperuricemia showed a strong positive association with MAFLD after controlled potential confounders. In the longitudinal cohorts, hyperuricemia at baseline was associated with the new-onset of MAFLD, with a hazard ratio (HR) of 1.765 (95% CI: 1.512, 2.060). Interestingly, baseline MAFLD was also associated with the subsequent incidence of hyperuricemia, with an HR of 1.245 (95% CI: 1.106, 1.400). The cross-lagged path analysis revealed a bidirectional relationship between hyperuricemia and MAFLD.

Conclusions: The results suggested that hyperuricemia and MAFLD form a vicious cycle, resulting in more deterioration of metabolic status.
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http://dx.doi.org/10.3389/fendo.2022.821689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889101PMC
April 2022
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