Publications by authors named "Jie Wang"

5,903 Publications

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Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

Blood Purif 2022 Aug 11:1-11. Epub 2022 Aug 11.

Department of Nephrology, Shanghai Sixth People's Hospital, Shanghai, China.

Introduction: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients.

Methods: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score.

Results: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively.

Conclusion: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.
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http://dx.doi.org/10.1159/000525225DOI Listing
August 2022

Deep-Blue Electroluminescence of Perovskites with Reduced Dimensionality Achieved by Manipulating Adsorption-Energy Differences.

Angew Chem Int Ed Engl 2022 Aug 9. Epub 2022 Aug 9.

Jilin University, College of physics, Qianjin Street, 130022, Changchun, CHINA.

The lagging development of deep-blue perovskite light-emitting diodes (PeLEDs) heavily impedes their practical applications in full-color display due to the absence of spectrally stable emitters and the mismatch of carrier injection capacity. Herein, we report highly efficient deep-blue PeLEDs through a new chemical strategy that addresses the dilemma for simultaneously constant electroluminescence (EL) spectra and high-purify phase in reduced-dimensional perovskites. The success lies in the control of adsorption-energy differences between phenylbutylamine (PBA) and ethylamine (EA) interacting with perovskites, which facilitates narrow n-value distribution. This approach leads to an increased exciton binding energy and enhanced surface potential, hence improving radiative recombination. As a result, an external quantum efficiency of 4.62% is achieved in PeLEDs with a stable EL peak at 457 nm, demonstrating the best reported result for deep-blue PeLEDs so far.
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http://dx.doi.org/10.1002/anie.202210322DOI Listing
August 2022

The effect of iron oxide types on the photochemical transformation of organic phosphorus in water.

Chemosphere 2022 Aug 6;307(Pt 2):135900. Epub 2022 Aug 6.

State Environmental Protection Key Laboratory of Soil Health and Green Remediation, College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address:

Iron oxides play an important role in the transport and transformation of organic phosphorus in aquatic environments. However, the effect of different types of iron oxide on the environmental fate of organic phosphorus has remained unclear. In this study, the photodegradation of the organic phosphorus compound adenosine triphosphate (ATP) via the activity of crystalline (goethite) and amorphous (ferrihydrite) iron oxides was investigated. It was found that ATP was photodegraded by goethite, resulting in the release of dissolved inorganic phosphate under simulated sunlight irradiation. The concentration of ATP on goethite decreased by 75% after 6 h of simulated sunlight irradiation, while the concentration of ATP on ferrihydrite decreased by only 22%. ATR-FTIR spectroscopy revealed that the intensity of the peaks for the P-O and PO stretching vibrations in the goethite-ATP complex decreased significantly more after simulated sunlight irradiation than did those for the ferrihydrite treatment. Combined with the higher TOC/TOC values for the goethite treatment, the results indicate that a more vigorous photochemical reaction took place in the presence of goethite than with ferrihydrite. Reactive oxygen species analysis also showed that hydroxyl and superoxide anion radicals were generated when goethite was exposed to simulated sunlight irradiation, while ferrihydrite did not exhibit this ability. Overall, this study highlights that the type of iron oxide is an important factor in the transformation of organic phosphorus in aquatic environments.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135900DOI Listing
August 2022

Characterization of indigenous coagulase-negative staphylococci isolated from Chinese spontaneously fermented meat products.

Microbiol Res 2022 Aug 4;263:127160. Epub 2022 Aug 4.

Department of Food Science and Agricultural Chemistry, Faculty of Agricultural and Environmental Sciences, McGill University, Sainte-Anne-de-Bellevue, Canada. Electronic address:

Technological, safety-related and volatile properties were analyzed in coagulase-negative staphylococci (CNS) isolates from Chinese spontaneously fermented meat products. A total of 107 CNS isolates were identified via 16 S rRNA sequencing, and the most recovered species were S. saprophyticus (53.3 %), S. edaphicus (12.1 %), and S. epidermidis (10.3 %). Among them, 58 CNS isolates belonging to 9 species were selected with higher activities of catalase, nitrate reductase, proteolysis, and lipolysis, as well as higher tolerance to stressful environmental conditions. Then, 7 CNS isolates belonging to 4 species were further selected based upon excellent technological characteristics, lack of hemolysis and antibiotic resistance, and a low production of biogenic amines. The volatile profiles of these 7 strains cultivated in pork broth was determined. S. casei No. 1 produced significant amounts of phenethyl alcohol, geraniol, and 3-methyl-butanol. S. xylosus No. 120 produced the highest amount of methyl ketones with the potential to provide dry-cured odor of fermented meats. The volatile profile was highly strain dependent. Several CNS identified in this study have the potential to be used as the starter cultures for fermented meat products.
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http://dx.doi.org/10.1016/j.micres.2022.127160DOI Listing
August 2022

Salidroside Ameliorates Ultraviolet-Induced Keratinocyte Injury by Inducing SIRT1-Dependent Autophagy.

Clin Cosmet Investig Dermatol 2022 2;15:1499-1508. Epub 2022 Aug 2.

Department of Dermatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People's Republic of China.

Introduction: Autophagy is an important process for maintaining intracellular homeostasis and is deregulated in ultraviolet B (UVB)-induced skin injury. Salidroside (SAL) is an active ingredient extracted from , which is a herbal medicine that has shown protection against ultraviolet (UV) radiation. Here, we investigated the functions and mechanisms of SAL on UVB-induced skin cell oxidative damage and autophagy.

Methods: Human immortalized keratinocyte cell line HaCaT was used as a cell model of UV injury. HaCaT cells were exposed to UVB irradiation and then incubated with SAL to investigate cell viability, lactate dehydrogenase (LSD) in culture media, intracellular reactive oxygen species (ROS) level, oxidative stress, autophagy, and regulatory effects on SIRT1 protein.

Results: SAL pretreatment (25, 50 and 100 μM) increased cell viability and inhibited LDH release in UVB-challenged HaCaT cells. SAL (100 μM) significantly reduced intracellular ROS level and suppressed oxidative stress, with increased MDA content and increased SOD activity. In addition, SAL pretreatment enhanced autophagy in UVB-irradiated HaCaT cells, increased protein expressions of Beclin-1 and ATG7, and decreased protein expression of P62. We also found that pretreatment with SAL increased the SIRT1 protein in irradiated HaCaT cells. SAL protected UVB-induced damage in a dependent manner on autophagy and SIRT1, as SAL-induced increase in viability was significantly attenuated by specific autophagy inhibitor Wortmannin (1 μM) or SIRT1 inhibitor EX-527 (100 nM).

Discussion: The present study results speculate that SAL suppresses UVB-induced injury and autophagy by enhancing SIRT1 expression.
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http://dx.doi.org/10.2147/CCID.S367233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356605PMC
August 2022

Impact of adjuvant chemotherapy on T1N0M0 breast cancer patients: a propensity score matching study based on SEER database and external cohort.

BMC Cancer 2022 Aug 8;22(1):863. Epub 2022 Aug 8.

Department of Thyroid and Breast Surgery, The First People's Hospital of Wenling, Chuanan Nan Road, Chengxi Street, Wenling, 317500, Zhejiang, China.

Background: There is no clear consensus on the benefits of adjuvant chemotherapy for tumor-node-metastasis (TNM) stage T1 (T1N0M0) breast cancer (BC). Our study investigated the effects of adjuvant chemotherapy on T1N0M0 BC patients.

Methods: Seventy-five thousand one hundred thirty-nine patients diagnosed with T1N0M0 BC were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of adjuvant chemotherapy on T1a, T1b, and T1cN0M0 BC, including various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further compare the results between adjuvant chemotherapy and no adjuvant chemotherapy. Additionally, 545 T1N0M0 BC patients treated at the Northern Jiangsu People's Hospital were included as an independent external validation cohort. Univariate and multivariate Cox analyses were used to confirm the effects of adjuvant chemotherapy in T1a, T1b, and T1cN0M0 BC. Survival curves for the different tumor grades and molecular subtypes were plotted using the Kaplan-Meier method.

Results: Adjuvant chemotherapy demonstrated a statistically significant improvement in overall survival (OS) in T1b and T1c BC, but not in T1a BC. Within T1b BC, adjuvant chemotherapy was found to have effects on grade III, and hormone receptor + (HoR +)/human epidermal growth factor receptor 2 + (HER2 +), HoR-/HER2 + , and HoR-/HER2- molecular subtypes, respectively. Adjuvant chemotherapy was beneficial to OS for grade II/III and T1c BC. Identical results were obtained after PSM. We also obtained similar results with external validation cohort, except that adjuvant chemotherapy made a difference in grade II and T1b BC of the external validation dataset.

Conclusions: Partial T1N0M0 BC patients with grade III T1bN0M0, patients with tumor grade II and III T1cN0M0, and excluding those with HoR + /HER2- subtype tumors, could obtain OS benefits from adjuvant chemotherapy.
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http://dx.doi.org/10.1186/s12885-022-09952-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358893PMC
August 2022

Prediction of Th1 and Cytotoxic T Lymphocyte Epitopes of and Evaluation of Their Potential in the Diagnosis of Tuberculosis in a Mouse Model and in Humans.

Microbiol Spectr 2022 Aug 8:e0143822. Epub 2022 Aug 8.

Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, China.

Latent tuberculosis infection (LTBI) is the primary source of tuberculosis (TB) but there is no suitable detection method to distinguish LTBI from active tuberculosis (ATB). In this study, five antigens of Mycobacterium tuberculosis belonging to LTBI and regions of difference (RDs) were selected to predict Th1 and cytotoxic T lymphocyte (CTL) epitopes. The immunodominant Th1 and CTL peptides were identified in mouse models, and their performance in distinguishing LTBI from ATB was determined in mice and humans. Ten Th1 and ten CTL immunodominant peptides were predicted and synthesized . The enzyme-linked immunosorbent spot assay results showed that the combination of five Th1 peptides (area under the curve [AUC] = 1, 0.0001; sensitivity = 100% and specificity = 93.33%), the combination of seven CTL peptides (AUC = 1, 0.0001; 100 and 95.24%), and the combination of four peptide pools (AUC = 1, 0.0001; sensitivity = 100% and specificity = 91.67%) could significantly discriminate mice with LTBI from mice with ATB or uninfected controls (UCs). The combined peptides or peptide pools induced significantly different cytokine levels between the three groups, improving their ability to differentiate ATB from LTBI. Furthermore, it was found that pool 2 could distinguish patients with ATB from UCs (AUC = 0.6728, 0.0041; sensitivity = 72.58% and specificity = 59.46%). The combination of Th1 and CTL immunodominant peptides derived from LTBI-RD antigens might be a promising strategy for diagnosing ATB and LTBI in mice and patients with ATB and uninfected controls. Latent tuberculosis infection (LTBI) is a challenging problem in preventing, diagnosing, and treating tuberculosis (TB). The innate and adaptive immune responses are essential for eliminating or killing the mycobacteria. Antigen-presenting cells (APCs) present and display mycobacterium peptides on their surfaces, and recognition between T cells and APCs is based on some essential peptides rather than the full-length protein. Therefore, the selection of candidate antigens and the prediction and screening of potential immunodominant peptides have become a key to designing a new generation of TB diagnostic biomarkers. This study is the first to report that the combination of Th1 and CTL immunodominant peptides derived from LTBI-RD antigens can distinguish LTBI from active TB (ATB) in animals and ATB patients from uninfected individuals. These findings provide a novel insight for discovering potential biomarkers for the differential diagnosis of ATB and LTBI in the future.
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http://dx.doi.org/10.1128/spectrum.01438-22DOI Listing
August 2022

The Effect of Individual Nursing on Anxiety and Depression in Patients with Temporomandibular Disorders.

Contrast Media Mol Imaging 2022 12;2022:7748696. Epub 2022 Jul 12.

Department of Oral and Maxillofacial, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Objective: This study aimed to explore the effects of individualized nursing in patients with temporomandibular disorders (TMD).

Methods: From June 2019 to April 2021, 80 patients with TMD were admitted to the First Affiliated Hospital of Wenzhou Medical University. Among them, 40 patients (control group, CG) received routine nursing and 40 patients (experimental group, EG) received individualized nursing. Functional exercise compliance, pain score, maximum mouth opening, nursing satisfaction questionnaire, self-rating anxiety scale, and self-rating depression scale were investigated.

Results: From June 2019 to April 2021, 81 patients with TMD were admitted to the First Affiliated Hospital of Wenzhou Medical University. Among them, 40 patients (control group) received routine care and 41 patients (experimental group) received individual care. There were no significant differences in mouth opening and pain score between the two groups before surgery ( > 0.05), but there were significant differences in mouth opening and pain score between the two groups 3 weeks after surgery. Patients' anxiety and depression were assessed by the SAS and SDS scores. Before nursing, the control group and experimental group ( < 0.05) had no significant difference. After nursing, the score of both groups decreased ( < 0.05). However, the score was lower in the experimental group, compared to the control group ( < 0.01).

Conclusion: In summary, individualized nursing can improve patients' physical condition and reduce negative emotions and complications. In light of this, the study needs further verification by a large sample randomized controlled trial.
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http://dx.doi.org/10.1155/2022/7748696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296338PMC
August 2022

Comparative analysis of aroma components and quality of after space mutation breeding.

Front Microbiol 2022 22;13:908329. Epub 2022 Jul 22.

College of Food Science, South China Agricultural University, Guangzhou, China.

Aim: The aroma-producing strain of GDMCC60675 was taken as the research object, the composition of aroma-producing substances of was studied, and the target strains of suitable for food additives were screened out by mutagenesis.

Methods: Mutants were obtained by space breeding. The colony morphology and cell morphology of the mutant strain were identified, the phylogenetic tree of the two strains was constructed, and the whole-genome sequences of the wild strain and the mutant strain were compared. The aroma components and key odor compounds of the two strains were analyzed and compared by HS-SPME-GC-MS and E-nose detection, and the data were processed by using the relative odor activity value (ROAV) analysis method.

Results: A mutant strain of was found with different characteristics of aroma production compared with wild-type . It was found that its colony morphology and cell morphology were similar. However, it was found that the aroma-producing substances produced by the two strains were different, and the key difference compound was phenyl ethyl alcohol, which also proved that the two strains were different, and the main aroma note was different.
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http://dx.doi.org/10.3389/fmicb.2022.908329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354409PMC
July 2022

Mechanism of dielectric barrier discharge plasma technology to improve the quantity of short-chain fatty acids in anaerobic fermentation of waste active sludge.

Front Microbiol 2022 22;13:963260. Epub 2022 Jul 22.

College of Environmental Science and Engineering, Donghua University, Shanghai, China.

The mechanism of improving the anaerobic fermentation performance of waste active sludge by using dielectric barrier discharge (DBD) plasma pretreatment technology was investigated. The maximum accumulation of short-chain fatty acids (SCFAs) was observed on the 7th day of anaerobic fermentation when the DBD power was 76.50 W, which was 1726.70 mg COD/L, 1.50 times of the control group. The ratio of acetic acid in DBD group was 9.30% higher than that in the control. Further mechanism research indicated that DBD pretreatment can destroy the structure of extracellular polymer substances and release organic substances such as protein and polysaccharide. The dissolved organic matter analysis indicated that the DBD technique could increase the release of biodegradable organics (eg., tyrosine proteins, soluble microbial by-products), thus accelerate the biotransformation of organic substance. Bacterial community structure analysis showed that the increase in the abundance of Firmicutes and Bacteroidetes and the decrease in the abundance of Proteobacteria in DBD group were beneficial to the accumulation of SCFAs. Besides, further archaeal analysis indicated that the decrease of sp. and . abundance in the DBD group facilitate acetic acid accumulation. This study demonstrated that the DBD technique can be used as an effective and potential pretreatment method to improve sludge anaerobic fermentation performance.
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http://dx.doi.org/10.3389/fmicb.2022.963260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355127PMC
July 2022

Functional characterization of bat IRF1 in IFN induction.

Dev Comp Immunol 2022 Aug 3:104500. Epub 2022 Aug 3.

Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Bats are natural hosts for various zoonotic viral diseases. However, they rarely show signs of disease infection with such viruses. During viral infection, members of the IRFs family induce the production of IFNβ and exert antiviral effects. However, the functions of bat IRFs remain unclear. In this study, the Tadarida brasiliensis IRF1 (TbIRF1) gene was first cloned and a series of bioinformatics studies were conducted. Results showed that bat IRF1 protein sequence showed a low similarity with IRF1s from other species. . RNA virus such as Newcastle disease virus (NDV-GFP), avian influenza virus (AIV) and vesicular stomatitis virus (VSV-GFP) infection of Tadarida brasiliensis 1 lung (TB 1 Lu) cells significantly promotes the expressions of IFNβ, PKR, and OAS1, and up-regulates the expression of TbIRF1. Overexpression of TbIRF1 markedly activates IFNβ promoter activity in a dose-dependent manner. Next, we constructed the TbIRF1 functional domain deletion plasmids and found that the DNA binding domain (DBD) is necessary for TbIRF1 to induce IFNβ expresison. In conclusion, the first bat IRF1 gene was cloned, and its functions in IFN induction were preliminarily identified.
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http://dx.doi.org/10.1016/j.dci.2022.104500DOI Listing
August 2022

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization.

EBioMedicine 2022 Aug 3;83:104200. Epub 2022 Aug 3.

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Electronic address:

Background: The mechanism of missense alteration at EGFR L792F in patients with non-small cell lung cancer resistant to osimertinib has not been sufficiently clarified. We aimed to explore the critical molecular events and coping strategies in osimertinib resistance due to acquired L792F mutation.

Methods: Circulating tumor DNA-based sequencing data of 1153 patients with osimertinib resistance were collected to illustrate the prevalence of EGFR L792F mutation. Sensitivity to osimertinib was tested with constructed EGFR 19Del/T790M-cis-L792F cell lines in vitro and in vivo. The correlation and linked pathways between M2 macrophage polarization and EGFR L792F-induced osimertinib resistance were investigated. Possible interventions to suppress osimertinib resistance by targeting IL-4 or STAT3 were explored.

Findings: The concomitant EGFR L792F was identified as an independent mutation following the acquisition of T790M after osimertinib resistance, in that 5 of the 946 patients with osimertinib resistance harbored EGFR T790M-cis-L792F mutation. Transfected EGFR 19Del/T790M-cis-L792F in cell lines had decreased sensitivity to osimertinib and enhanced infiltrating macrophage with M2 polarization. Silico analyses confirmed the role of M2 polarization in osimertinib resistance induced by EGFR T790M-cis-L792F mutation. EGFR T790M-cis-L792F mutation upregulated phosphorylation of STAT3 Tyr705 and promoted its specific binding to IL4 promoter, enhancing IL-4 expression and secretion and inducing macrophage M2 polarization. Furthermore, blockade of STAT3/IL-4 (SH-4-54 or dupilumab) suppressed macrophage M2 polarization and regressed tumor sensitivity to osimertinib.

Interpretation: Our results proved that targeting EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC.

Funding: This work was supported by the National Natural Science Foundation of China (81871889, 82072586, 81902910), Beijing Natural Science Foundation (7212084, 7214249), the China National Natural Science Foundation Key Program (81630071), the National Key Research and Development Project (2019YFC1315704), CAMS Innovation Fund for Medical Sciences (CIFMS 2021-1-I2M-012), Aiyou Foundation (KY201701) and CAMS Key Laboratory of translational research on lung cancer (2018PT31035).
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http://dx.doi.org/10.1016/j.ebiom.2022.104200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358434PMC
August 2022

Acoustic radiation force of a sphere with a hemispherically split boundary condition in a plane wave.

J Acoust Soc Am 2022 Jul;152(1):501

Shaanxi Key Laboratory of Ultrasonics, School of Physics and Information Technology, Shaanxi Normal University, Xi'an 710119, People's Republic of China.

In this paper, an analytical expression of the acoustic radiation force (ARF) for a spherical particle with a hemispherically split impedance boundary in a plane wave is deduced. Numerical calculations are carried out by considering the effect of the magnitude and phase of the acoustic impedance on the ARF. Computation results show that the increase in the magnitude of the acoustic impedance results in an overall decrease in the ARF, whereas the phase of the acoustic impedance results in a decrease in the ARF in the low frequency region. As the frequency increases, the positive phase angle leads to a decrease in the ARF, and the negative phase angle causes the ARF to increase rapidly. For a hemispherically split impedance sphere, the values of the ARF range from those of the rigid sphere and uniform impedance sphere. The finite-element models for the calculation of the ARF of a hemispherically split impedance boundary sphere are established and the correctness of the analytical theory is proved by numerical comparison. This work is expected to contribute theoretical support to the acoustic manipulation of particles with a nonuniform hemispherically split structure.
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http://dx.doi.org/10.1121/10.0012736DOI Listing
July 2022

Engineered living bioassemblies for biomedical and functional material applications.

Curr Opin Biotechnol 2022 Aug 2;77:102756. Epub 2022 Aug 2.

Canary Center at Stanford for Cancer Early Detection, Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Department of Radiology, School of Medicine Stanford University, Palo Alto, CA 94304-5427, USA.

Recent breakthroughs in biofabrication of bioasemblies, consisting of the engineered structures composed of biological or biosynthetic components into a single construct, have found a wide range of practical applications in medicine and engineering. This review presents an overview of how the bottom-up assembly of living entities could drive advances in medicine, by developing tunable biological models and more precise methods for quantifying biological events. Moreover, we delve into advances beyond biomedical applications, where bioassemblies can be manipulated as functional robots and construction materials. Finally, we address the potential challenges and opportunities in the field of engineering living bioassemblies, toward building new design principles for the next generation of bioengineering applications.
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http://dx.doi.org/10.1016/j.copbio.2022.102756DOI Listing
August 2022

Fabrication of Adsorption-Type Hierarchical Functional Films by Using a Facile Swollen Based Breath Figure Method.

Macromol Rapid Commun 2022 Aug 4:e2200403. Epub 2022 Aug 4.

School of Chemistry and Materials Science, Hubei Engineering University, Xiaogan, Hubei, 432000, China.

The morphology transition from primary to hierarchical adsorption-type microporous domains of amphiphilic block copolymer (BCP) honeycomb-structured films is demonstrated by a facile swollen based breath figure (BF) method. The characteristic parameters of poly(4-vinylpyridine)-block-polystyrene (P4VP-b-PS) hierarchical micro- and submicro-porous films can be controlled by changing the length of segments or subsequent swelling conditions. A plausible mechanism is demonstrated in this research. A typical amphiphilic BCP with very low volume content of hydrophilic blocks (f ≤ 0.050) can efficiently stabilize water droplets and inherently assist in the formation of morphology transition. This BCP film can be used for Cr(VI) removal from wastewater, which additionally has enormous potential application in the field of novel optical devices, soft lithography, size-selective separation, etc. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/marc.202200403DOI Listing
August 2022

Retrospective motion correction for preclinical/clinical MRI based on conditional GAN with entropy loss.

NMR Biomed 2022 Aug 4:e4809. Epub 2022 Aug 4.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, China.

Multi-shot scan MRI acquisition is inherently sensitive to motion, and motion artifact reduction is essential for improving the image quality in MRI. This work proposes and validates a new end-to-end motion correction method for the multi-shot sequence that incorporates the conditional Generative Adversarial Network with Minimum Entropy of MRI images (cGANME). The cGANME network contains an encoder-decoder generator to obtain the motion-corrected images and a PatchGAN discriminator to classify the image as either real (motion-free) or fake (motion-corrected). The entropy of the images is set as one loss item in the cGAN's loss as the entropy increases monotonically with the motion artifacts. The ablation experiment of the different weights of the entropy loss is performed to evaluate the function of entropy loss. The preclinical dataset is acquired with the FSE pulse sequence on a 7.0T scanner. After the simulation, we have 10080/2880/1440 slices for training, testing, and validating, respectively. The clinical data set is downloaded from the Human Connection Project website, 11300/3500/2000 slices are used for training, testing, and validating after simulation. Extensive experiments for different motion patterns, motion levels, and protocol parameters demonstrate that cGANME outperforms traditional and some state-of-art deep learning-based methods. In addition, we test cGANME on in vivo awake rats and mitigate the motion artifacts, indicating the model has a certain generalization ability.
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http://dx.doi.org/10.1002/nbm.4809DOI Listing
August 2022

3D GAN image synthesis and dataset quality assessment for bacterial biofilm.

Bioinformatics 2022 Aug 4. Epub 2022 Aug 4.

C.L. Brown Department of Electrical and Computer Engineering, University of Virginia, Charlottesville, VA, 22904, USA.

Motivation: Data-driven deep learning techniques usually require a large quantity of labeled training data to achieve reliable solutions in bioimage analysis. However, noisy image conditions and high cell density in bacterial biofilm images make 3D cell annotations difficult to obtain. Alternatively, data augmentation via synthetic data generation is attempted, but current methods fail to produce realistic images.

Results: This paper presents a bioimage synthesis and assessment workflow with application to augment bacterial biofilm images. 3D cyclic generative adversarial networks (GAN) with unbalanced cycle consistency loss functions are exploited in order to synthesize 3D biofilm images from binary cell labels. Then, a stochastic synthetic dataset quality assessment (SSQA) measure that compares statistical appearance similarity between random patches from random images in two datasets is proposed. Both SSQA scores and other existing image quality measures indicate that the proposed 3D Cyclic GAN, along with the unbalanced loss function, provides a reliably realistic (as measured by mean opinion score) 3D synthetic biofilm image. In 3D cell segmentation experiments, a GAN-augmented training model also presents more realistic signal-to-background intensity ratio and improved cell counting accuracy.

Availability And Implementation: https://github.com/jwang-c/DeepBiofilm.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btac529DOI Listing
August 2022

The West China Hospital radiographic classification for fibrous dysplasia in femur and adjacent bones: A retrospective analysis of 205 patients.

Orthop Surg 2022 Aug 4. Epub 2022 Aug 4.

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

Objective: This study aims to investigate the reliability and clinical outcome of a newly developed classification system for patients with fibrous dysplasia (FD) of the femur and adjacent bones, optimizing its evaluation and management.

Methods: A total of 205 patients (121 female and 84 male) with FD in the femur and adjacent bones were included in this retrospective study. All affected femurs were measured and treated based on this classification at our institution between 2009 and 2019. Based on previous studies and extensive clinical follow-up, we cautiously proposed the West China Hospital radiographic classification for FD in femur and adjacent bones following corresponding treatment options. There are five types with five radiographic features, including proximal femur bone loss, coxa vara, femoral shaft deformity, genu valgum, and hip arthritis. The intraobserver and interobserver reproducibility of this classification was assessed by four observers using the Cohen kappa statistic. The clinical outcome was evaluated using the criteria of Guille.

Results: At a median follow-up of 60 months (range 6-120), 205 patients (median 34.8 years old, range 18-73 years old) were categorized into the following five types: Type I 31.7%, Type II 30.2%, Type III 20.5%, Type IV 10.2%, and Type V 7.3%. The mean interobserver and intraobserver kappa scores were 0.85 (range 0.77-0.89) and 0.85 (range 0.79-0.92), respectively. For clinical outcomes, there was no significant difference in the postoperative Guille score for Type I patients (mean 9.01 ± 1.22). There was a significant increase in the postoperative Guille score in Type II, III, IV, and V, compared to the preoperative values (P < 0.01). For complications, two Type III patients reported pain, and one Type III patient had mild-to-moderate Trendelenburg gait. One Type IV patient had a mild Trendelenburg gait. And two Type V patients still had mild limping.

Conclusion: This classification is reproducible and serves as a tool for evaluating and treating FD in the femur and adjacent bones. Therefore, we recommend this classification for the diagnosis and treatment of FD-related deformities in the femur and adjacent bones.
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http://dx.doi.org/10.1111/os.13404DOI Listing
August 2022

HemoglobinA1c Is a Risk Factor for Changes of Bone Mineral Density: A Mendelian Randomization Study.

Front Endocrinol (Lausanne) 2022 18;13:942878. Epub 2022 Jul 18.

Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: As a valuable blood glucose measurement, HemoglobinA1c (HbA1c) is of great clinical value for diabetes. However, in previous observational studies, studies on its effect on bone mineral density (BMD) have different results. This study aimed to use Mendelian randomization (MR) to assess the effect of HbA1c on bone mineral density and fracture risk, and try to further explore whether this association was achieved through glycemic or non-glycemic factors.

Methods: Take HbA1c measurement as exposure, and BMD estimated from quantitative heel ultrasounds (eBMD) and bone fractures as outcomes. Two-Sample MR Analysis was conducted to assess the causal effect of HbA1C on heel BMD and risk fracture. Then, we performed the analysis using two subsets of these variants, one related to glycemic measurement and the other to erythrocyte indices.

Results: Genetically increased HbA1C was associated with the lower heel eBMD [odds ratio (OR) 0.91 (95% CI 0.87, 0.96) per %-unit, P = 3 × 10-4(IVW)]. Higher HbA1C was associated with lower heel eBMD when using only erythrocytic variants [OR 0.87 (0.82, 0.93), P=2× 10-5(IVW)]; However, when using only glycemic variants, this casual association does not hold. In further MR analysis, we test the association of erythrocytic traits with heel eBMD.

Conclusion: Our study revealed the significant causal effect of HbA1c on eBMD, and this causal link might achieve through non-glycemic pathways (erythrocytic indices).
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http://dx.doi.org/10.3389/fendo.2022.942878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339617PMC
August 2022

Compensatory thalamocortical functional hyperconnectivity in type 2 Diabetes Mellitus.

Brain Imaging Behav 2022 Aug 4. Epub 2022 Aug 4.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, 230022, Hefei, China.

Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.
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http://dx.doi.org/10.1007/s11682-022-00710-0DOI Listing
August 2022

CRISPR/Cas9-mediated epigenetic editing tool: An optimized strategy for targeting de novo DNA methylation with stable status via homology directed repair pathway.

Biochimie 2022 Jul 31. Epub 2022 Jul 31.

National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China. Electronic address:

With the development of epigenetic engineering tools for manipulating DNA methylation at the desired locus, the stable maintenance of targeted methylation status in edited cells after division poses a major obstacle. Transient methylation levels, along with the reversible inhibition of the desired genes, by some epigenetic editing techniques, limit their further application in functional and therapeutic studies of critical regulators in the cancer epigenome. In this study, we utilized CRISPR/Cas9-mediated the homology-directed repair (HDR) pathway following double-strand breaks (DSBs) information to target de novo methylation of the vital epigenetic biomarker, O-methylguanine-DNA methyltransferase (MGMT). Based on synthetic single and double stranded methylated repair templates, DNA methylation patterns can be incorporated into the endogenous MGMT gene. In addition, we observed upregulation of DNA methyltransferases (DNMTs) in edited HeLa cells. In particular, we employed an optimized method of using the DNA ligase IV inhibitor SCR7 to markedly enhance the insertion efficiency induced by the long methylated repair template, contributing to the induction of stable methylation alterations through epigenetic recombination after cell division. Additionally, our study confirmed that CRISPR/Cas9-mediated target methylation in a site-specific manner enabled the maintenance of gene silencing in vitro and in vivo. Collectively, we show that a combination of CRISPR/Cas9 components, SCR7 treatment, and the long methylated HDR template can enhance CRISPR/Cas9-directed epigenomic editing efficiency and further induce stable effects on methylation modifications and transcriptional suppression.
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http://dx.doi.org/10.1016/j.biochi.2022.07.013DOI Listing
July 2022

Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity.

Autophagy 2022 Aug 3. Epub 2022 Aug 3.

Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Age-related macular degeneration (AMD), the leading cause of blindness among the elderly, is without treatment for early disease. Degenerative retinal pigment epithelial (RPE) cell heterogeneity is a well-recognized but understudied pathogenic factor. Due to the daily phagocytosis of photoreceptor outer segments, unique photo-oxidative stress, and high metabolism for maintaining vision, the RPE has robust macroautophagy/autophagy, and mitochondrial and antioxidant networks. However, the autophagy subtype, mitophagy, in the RPE and AMD is understudied. Here, we found decreased PINK1 (PTEN induced kinase 1) in perifoveal RPE of early AMD eyes. PINK1-deficient RPE have impaired mitophagy and mitochondrial function that triggers death-resistant epithelial-mesenchymal transition (EMT). This reprogramming is mediated by novel retrograde mitochondrial-nuclear signaling (RMNS) through superoxide, NFE2L2 (NFE2 like bZIP transcription factor 2), TXNRD1 (thioredoxin reductase 1), and phosphoinositide 3-kinase (PI3K)-AKT (AKT serine/threonine kinase) that induced canonical transcription factors ZEB1 (zinc finger E-box binding homeobox 1) and SNAI1 (Snail family transcriptional repressor 1) and an EMT transcriptome. NFE2L2 deficiency disrupted RMNS that paradoxically normalized morphology but decreased function and viability. Thus, RPE heterogeneity is defined by the interaction of two cytoprotective pathways that is triggered by mitophagy function. By neutralizing the consequences of impaired mitophagy, an antioxidant dendrimer tropic for the RPE and mitochondria, EMT (a recognized AMD alteration) was abrogated to offer potential therapy for early AMD, a stage without treatment.
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http://dx.doi.org/10.1080/15548627.2022.2109286DOI Listing
August 2022

Toxoplasma gondii dense granule protein 3 promotes endoplasmic reticulum stress-induced apoptosis by activating the PERK pathway.

Parasit Vectors 2022 Aug 2;15(1):276. Epub 2022 Aug 2.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.

Background: Toxoplasma gondii is a neurotropic single-celled parasite that can infect mammals, including humans. Central nervous system infection with T. gondii infection can lead to Toxoplasma encephalitis. Toxoplasma infection can cause endoplasmic reticulum (ER) stress and unfolded protein response (UPR) activation, which ultimately can lead to apoptosis of host cells. The dense granule protein GRA3 has been identified as one of the secretory proteins that contribute to the virulence of T. gondii; however, the mechanism remains enigmatic.

Methods: The expression of the GRA3 gene in RH, ME49, Wh3, and Wh6 strains was determined using quantitative real-time polymerase chain reaction (qRT-PCR). pEGFP-GRA3 was constructed by inserting Chinese 1 Wh6 GRA3 (GRA3) cDNA into a plasmid encoding the enhanced GFP. Mouse neuro2a (N2a) cells were transfected with either pEGFP or pEGFP-GRA3 (GRA3) and incubated for 24-36 h. N2a cell apoptosis and ER stress-associated proteins were determined using flow cytometry and immunoblotting. Furthermore, N2a cells were pretreated with GSK2656157 (a PERK inhibitor) and Z-ATAD-FMK (a caspase-12 inhibitor) before GRA3 transfection, and the effect of the inhibitors on GRA3-induced ER stress and apoptosis were investigated.

Results: GRA3 gene expression was higher in the less virulent strains of type II ME49 and type Chinese 1 Wh6 strains compared with the virulent strains of type I RH strain and type Chinese 1 Wh3 strain. Transfection with GRA3 plasmid induced neuronal apoptosis and increased the expression of GRP78, p-PERK, cleaved caspase-12, cleaved caspase-3, and CHOP compared with the control vector. Pretreatment with GSK2656157 and Z-ATAD-FMK decreased apoptosis in N2a cells, and similarly, ER stress- and apoptosis-associated protein levels were significantly decreased.

Conclusion: GRA3 induces neural cell apoptosis via the ER stress signaling pathway, which could play a role in toxoplasmic encephalitis.
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http://dx.doi.org/10.1186/s13071-022-05394-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344675PMC
August 2022

Single-cell analysis reveals differences among iNKT cells colonizing peripheral organs and identifies Klf2 as a key gene for iNKT emigration.

Cell Discov 2022 Aug 2;8(1):75. Epub 2022 Aug 2.

Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, USA.

Invariant natural killer T cell (iNKT) subsets are differentially distributed in various immune organs. However, it remains unclear whether iNKT cells exhibit phenotypical and functional differences in different peripheral organs and how thymic iNKT cells emigrate to peripheral organs. Here, we used single-cell RNA-seq to map iNKT cells from peripheral organs. iNKT1 cells from liver, spleen, and lymph node appear to have distinct phenotypic profiles and functional capabilities. However, iNKT17 transcriptomes were comparable across peripheral organs. In addition, by integrating data with a thymic iNKT cell study, we uncovered a transient population of recent thymic emigrants, a cluster of peripheral iNKT cells with high expression of transcription factor Kruppel-like factor 2 (Klf2). Deletion of Klf2 led to a severe impairment of iNKT differentiation and migration. Our study revealed that iNKT subsets are uniquely distributed in peripheral organs with some inter-local tissue variation, especially for iNKT1 cell, and identified Klf2 as a rheostat for iNKT cell migration and differentiation.
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http://dx.doi.org/10.1038/s41421-022-00432-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343440PMC
August 2022

Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy.

Neoplasia 2022 Jul 29;32:100824. Epub 2022 Jul 29.

The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United States.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease with genetic and environmental parameters that influence cell metabolism. Because of the complex interplay of environmental factors within the tumor microenvironment (TME) and the profound impact of these factors on the metabolic activities of tumor and immune cells, there is an emerging interest to advance the understanding of these diverse metabolic phenotypes in the TME. High levels of adenosine are characteristic of the TME, and adenosine can have a significant impact on both tumor cell growth and the immune response. Consistent with this, we showed in NSCLC data from TCGA that high expression of the A2BR leads to worse outcome and that expression of A2BR may be different for different mutation backgrounds. We then investigated the metabolic reprogramming of tumor cells and immune cells (T and dendritic cells) by adenosine. We used A2AR and A2BR antagonism or agonism as well as receptor knockout animals to explore whether these treatments altered specific immune compartments or conferred specific therapeutic vulnerabilities. Using the seahorse assay, we found that an A2BR antagonist modulates oxidative stress homeostasis in NSCLC cell lines. In addition, we found distinct metabolic roles of A2AR and A2BR receptors in T cell activation and dendritic cell maturation. These data suggest potential mechanisms and therapeutic benefits of A2 receptor antagonist therapy in NSCLC.
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http://dx.doi.org/10.1016/j.neo.2022.100824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344351PMC
July 2022

Combined and Modified Gibson and Ilioinguinal Approaches in Type II + III Internal Hemipelvectomy for Periacetabular Tumors.

Front Oncol 2022 13;12:934812. Epub 2022 Jul 13.

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

Background: The routine iliofemoral approach and its modifications in type II+III resection require extensive skin incision and massive periacetabular muscle detachment, leading to prolonged hospital stay, increased complication incidence, and impaired lower limb function. Under the management of an enhanced recovery after surgery (ERAS) protocol, a combined and modified Gibson and ilioinguinal (MGMII) approach was used to avoid unnecessary soft tissue trauma during tumor resection and therefore advantageous to patients' return to normal life.

Methods: Twenty-five patients with type II + III (including type II) periacetabular tumors who underwent reconstruction with 3D printed customized endoprostheses at our center between January 2017 and March 2019 were included in this study. There were 13 cases using MGMII approach and 12 cases using iliofemoral approach. The operation duration and blood loss were assessed by chart review. The surgical margin was evaluated by the histopathological studies. The reconstruction accuracy, the abductor muscle strength, the 1993 version of the Musculoskeletal Tumor Society (MSTS-93), the Harris Hip scores (HHS), and the limp score were evaluated. Complications were recorded after reviewing the patients' records.

Results: The operative duration and blood loss in MGMII group were shorter than those in the iliofemoral group, but the postoperative hemoglobin was slightly higher than that in the iliofemoral group. The MGMII group had stronger postoperative hip abductors, better functional restoration, and relatively fewer patients with higher limp scores. No complication was observed in the MGMII group. In the iliofemoral group, three patients encountered wound healing delay, and one patient suffered deep infection.

Conclusions: The MGMII approach can better expose the posterior column of the acetabulum, especially the ischial tuberosity, which is beneficial for avoiding tumor rupture during resection. The MGMII approach also helps to preserve residual muscle function, such as the origin of the gluteus medius, while ensuring the extent of resection.
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http://dx.doi.org/10.3389/fonc.2022.934812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326475PMC
July 2022

Systemic Inflammation Response Index Is a Promising Prognostic Marker in Elderly Patients With Heart Failure: A Retrospective Cohort Study.

Front Cardiovasc Med 2022 14;9:871031. Epub 2022 Jul 14.

Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.

Background: Heart failure (HF) is a clinical syndrome caused by ventricular dysfunction, which leads to the decline of activity tolerance and repeated hospitalization, which seriously affects the quality of life and is the main cause of death of the elderly. It has long been observed that the pathophysiological mechanism of HF is associated with systemic inflammation. This study aims to explore the association between the systemic inflammation response index (SIRI), a novel biomarker of inflammation, and outcomes in elderly patients with HF.

Methods: Data was extracted from the Medical Information Mart data for Intensive Care III (MIMIC-III) database and the Second Affiliated Hospital of Wenzhou Medical University. The primary outcome was 90-day all-cause mortality. The secondary outcomes included 1-year all-cause mortality, the length of hospital or intensive care unit (ICU) stay, and the need for renal replacement therapy (RRT). Cox proportional hazards regression, linear regression, and logistic regression models were used to assess the association between SIRI levels and all-cause mortality, the length of hospital or ICU stay, the need for RRT, respectively. Moreover, Pearson correlation analysis was conducted to evaluate the correlation between SIRI and C-reactive protein (CRP).

Results: This study cohort included 3,964 patients from the MIMIC-III database and 261 patients from the Second Affiliated Hospital of Wenzhou Medical University. The result suggested that SIRI was independently associated with the 90-day, and 1-year all-cause mortality in elderly patients with HF (tertile 3 vs. tertile 1: adjusted HR, 95% CI: 1.41 (1.18, 1.68), 1.19 (1.03, 1.37); trend = 0.0013, 0.0260; respectively). Elevated SIRI was associated with increased the length of hospital or ICU stay after adjusting for multiple confounders (tertile 3 vs. tertile 1: , 95% CI: 0.85 (0.16, 1.54); 0.62 (0.18, 1.06); trend = 0.0095, 0.0046; respectively). Furthermore, we found that patients with higher SIRI levels were more likely to require RRT (tertile 3 vs. tertile 1: OR, 95% CI: 1.55 (1.06, 2.28); trend = 0.0459). Moreover, we confirmed that SIRI was statistically positively correlated with CRP (correlation coefficient = 0.343, <0.001).

Conclusions: SIRI could be a novel promising inflammatory biomarker for predicting all-cause mortality in elderly patients with HF. And the patients with higher SIRI values had the longer length of hospital or ICU stay and were more likely to require for RRT. Of note, this study also verified a statistically significant positive correlation between SIRI and the inflammatory marker CRP, highlighting the importance of systemic inflammation as a determinant of outcome in patients with HF.
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http://dx.doi.org/10.3389/fcvm.2022.871031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330028PMC
July 2022

Identification of Sex-Specific Plasma Biomarkers Using Metabolomics for Major Depressive Disorder in Children and Adolescents.

Front Psychiatry 2022 14;13:929207. Epub 2022 Jul 14.

National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Children and adolescents are at a high risk of major depressive disorder (MDD) with known sex differences in epidemiology. However, there are currently no objective laboratory-based sex-specific biomarkers available to support the diagnoses of male and female patients with MDD.

Methods: Here, a male set of 42 cases and 27 healthy controls (HCs) and a female set of 42 cases and 22 HCs were recruited. This study investigated the sex differences of plasma metabolite biomarkers in young patients with MDD by the application of ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry.

Results: The metabolic profiles showed clear separations in both male and female sets. In total, this study identified 57 male-related and 53 female-related differential metabolites. Compared with HCs, both male and female subjects with MDD displayed four significantly altered pathways. Notably, biliverdin was selected as an independent diagnostic male-specific biomarker with an area under the receiver operating characteristic curve of 0.966, and phosphatidylcholine (10:0/14:1) was selected as a female-specific biomarker, achieving an area under the curve (AUC) of 0.957.

Conclusion: This metabolomics study may aid in the development of a plasma-based test for the diagnosis of male and female children and adolescents with MDD, as well as give new insight into the pathophysiology of sex differences in children and adolescents with MDD.
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http://dx.doi.org/10.3389/fpsyt.2022.929207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329558PMC
July 2022

Case Report: A novel mutation in Werner syndrome patient with diabetic foot disease and myelodysplastic syndrome.

Front Endocrinol (Lausanne) 2022 15;13:918979. Epub 2022 Jul 15.

Endocrine and Metabolic Disease Center, Medical Key Laboratory of Hereditary Rare Diseases of Henan, Luoyang Sub-Center of National Clinical Research Center for Metabolic Diseases, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.

Werner syndrome is an autosomal recessive rare disease caused by a gene mutation, which is rarely reported in the Chinese population. We report the clinical and genetic data of a Chinese patient with Werner syndrome. The proband was a 40-year-old male patient who presented with diabetic foot ulcers, accompanied by short stature, cataracts, hypogonadism, and hair thinning, and myelodysplastic syndrome (MDS) occurred after 18 months. Genetic sequencing showed there were compound heterozygous mutations as c.3384-1G>C and c.3744dupA in the gene. The c.3744dupA mutation is a novel pathogenic variation for Werner syndrome.
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http://dx.doi.org/10.3389/fendo.2022.918979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334726PMC
July 2022
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