Publications by authors named "Xiaohong Wang"

1,255 Publications

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Optically Programmable Circularly Polarized Photodetector.

ACS Nano 2022 Aug 8. Epub 2022 Aug 8.

National Engineering Lab of Special Display Technology, State Key Lab of Advanced Display Technology, Academy of Optoelectronic Technology, Hefei University of Technology, Hefei 230009, China.

The detection of circularly polarized light (CPL) has aroused wide attention from both the scientific and industrial communities. However, from the optical activity of the chiral layer in the conventional CPL photodetectors, the sign inversion property is difficult to be achieved. As a result, great challenges arise during the preparation of miniaturized and integrated devices for tunable CPL detection applications. Along these lines, in this work, by taking advantage of the CPL-induced chirality characteristics of the achiral poly(9,9-di--hexylfluorene--benzothiadiazole) (F6BT) and the good crystalline and electrical properties of the poly(3-hexylthiophene) (P3HT) film, an optically programmable CPL photodetector was fabricated. Interestingly, the device exhibited excellent discrimination between left- and right-handed CPL, while the maximum anisotropy factor of responsivity was 0.425. On top of that, the rigorously controlled chirality of the F6BT and the capability to be switched by the handedness of CPL was leveraged to realize the switchable detection of both L-CPL and R-CPL. Furthermore, a CPL photodetector array was fabricated, and the image processing and cryptographic characteristics were demonstrated. The proposed device configuration can find application in various scientific fields, including photonics, emission, conversion, or sensing with CPL but also is anticipated to play a key role for imaging and anticounterfeiting applications.
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http://dx.doi.org/10.1021/acsnano.2c03746DOI Listing
August 2022

The role of synergistic interplay among proactive personality, leader creativity expectations, and role clarity in stimulating employee creativity.

Front Psychol 2022 22;13:699411. Epub 2022 Jul 22.

School of Humanities, Social Sciences & Law, Harbin Institute of Technology, Harbin, China.

This study investigates the interplay among proactive personality, leader creativity expectations, and role clarity in stimulating employee creativity based on the theoretical frameworks of role theory. Questionnaires were distributed to obtain 290 leader-employee dyads from China to examine hypotheses conditional process analysis. The results show that proactive personality has a positive effect on employee creativity, leader creativity expectations did not play a significant moderating role on the relationship between proactive personality and employee creativity. The interaction between leader creativity expectations and role clarity has a significant moderating effect on the relationship between proactive personality and employee creativity. These findings are discussed in terms of their theoretical and practical significance.
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http://dx.doi.org/10.3389/fpsyg.2022.699411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354752PMC
July 2022

Stacked dilated convolutions and asymmetric architecture for U-Net-based medical image segmentation.

Comput Biol Med 2022 Jul 21;148:105891. Epub 2022 Jul 21.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, MA, USA.

Deep learning has been widely utilized for medical image segmentation. The most commonly used U-Net and its variants often share two common characteristics but lack solid evidence for the effectiveness. First, each block (i.e., consecutive convolutions of feature maps of the same resolution) outputs feature maps from the last convolution, limiting the variety of the receptive fields. Second, the network has a symmetric structure where the encoder and the decoder paths have similar numbers of channels. We explored two novel revisions: a stacked dilated operation that outputs feature maps from multi-scale receptive fields to replace the consecutive convolutions; an asymmetric architecture with fewer channels in the decoder path. Two novel models were developed: U-Net using the stacked dilated operation (SDU-Net) and asymmetric SDU-Net (ASDU-Net). We used both publicly available and private datasets to assess the efficacy of the proposed models. Extensive experiments confirmed SDU-Net outperformed or achieved performance similar to the state-of-the-art while using fewer parameters (40% of U-Net). ASDU-Net further reduced the model parameters to 20% of U-Net with performance comparable to SDU-Net. In conclusion, the stacked dilated operation and the asymmetric structure are promising for improving the performance of U-Net and its variants.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105891DOI Listing
July 2022

Protective effects of CRTH2 suppression in dry age-related macular degeneration.

Biochem Biophys Res Commun 2022 Jul 14;624:8-15. Epub 2022 Jul 14.

Tianjin Medical University, Tianjin, China; Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China; School of Medicine Nankai University, China. Electronic address:

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Oxidative stress-induced retinal pigment epithelium (RPE) cell apoptosis is a crucial pathogenic hallmark in AMD. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a prostaglandin (PG) D2 receptor, has been implicated in various pathophysiological events, especially inflammation and stress-induced cell apoptosis. However, its specific role in AMD is not fully understood. Here we studied the effect of CRTH2 on AMD. Our results showed that when stimulated by HO, CRTH2 mRNA expression in cells tended to increase. Flow cytometry revealed that the CRTH2 inhibitor could protect the RPE from apoptosis. After NaIO injection, a larger area of retinal degeneration was observed in wild-type mice than in CRTH2 mice. Optical coherence tomography (OCT) and Hematoxylin and Eosin (H&E) staining of retinal sections showed that sodium iodate-induced loss of photoreceptor cells was reduced in CRTH2 mice after treatment; TUNEL-positive cells were mostly found in the outer nuclear layer. In the control group, NaIO stimulation increased the number of TUNEL-positive cells, whereas the percentage of TUNEL-positive cells was significantly lower in CRTH2 mice. Similarly, the CRTH2 receptor inhibitor CAY10471 similarly inhibited sodium iodate-induced retinal damage. Our results suggest that targeting CRTH2 is a promising therapeutic strategy for the treatment of progressive retinal degeneration in AMD.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.003DOI Listing
July 2022

Comprehensive Analysis of TRP Channel-Related Genes in Patients With Triple-Negative Breast Cancer for Guiding Prognostic Prediction.

Front Oncol 2022 7;12:941283. Epub 2022 Jul 7.

Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital, Binzhou, China.

Background: Triple-negative breast cancer (TNBC) is a special subtype of breast cancer. Transient Receptor Potential (TRP) channel superfamily has emerged as a novel and interesting target in a variety of tumors. However, the association of TRP channel-related genes with TNBC is still unclear.

Methods: The The Cancer Genome Atlas (TCGA)-TNBC and GSE58812 datasets were downloaded from the public database. The differentially expressed TRP channel-related genes (DETGs) were screened by limma package, and mutations of the above genes were analyzed. Subsequently, new molecular subtypes in TNBC-based DETGs were explored by consensus clustering analysis. In addition, Lasso-Cox regression analysis was used to divide it into two robust risk subtypes: high-risk group and low-risk group. The accuracy and distinguishing ability of above models were verified by a variety of methods, including Kaplan-Meier survival analysis, ROC analysis, calibration curve, and PCA analysis. Meanwhile, CIBERSORT algorithm was used to excavate status of immune-infiltrating cells in TNBC tissues. Last, we explored the therapeutic effect of drugs and underlying mechanisms of risk subgroups by pRRophetic package and GSEA algorithm, respectively.

Results: A total of 19 DETGs were identified in 115 TNBC and 113 normal samples from TCGA database. In addition, missense mutation and SNP were the most common variant classification. According to Lasso-Cox regression analysis, the risky formula performed best when nine genes were used: TRPM5, TRPV2, HTR2B, HRH1, P2RY2, MAP2K6, NTRK1, ADCY6, and PRKACB. Subsequently, Kaplan-Meier survival analysis, ROC analysis, calibration curve, and Principal Components Analysis (PCA) analysis showed an excellent accuracy for predicting OS using risky formula in each cohort (P < 0.05). Specifically, high-risk group had a shorter OS compared with low-risk group. In addition, T-cell CD4 memory activated and macrophages M1 were enriched in normal tissues, whereas Tregs were increased in tumor tissues. Note that the low-risk group was better therapeutic effect to docetaxel, doxorubicin, cisplatin, paclitaxel, and gemcitabine than the high-risk group (P < 0.05). Last, assays, Quantitative Real-time PCR (qRT-PCR) indicated that TRPM5 was significantly highly expressed in MDA-MB-231 and MDA-MB-468 cells compared with that in MCF-10A cells (P < 0.01).

Conclusion: We identified a risky formula based on expression of TRP channel-related genes that can predict prognosis, therapeutic effect, and status of tumor microenvironment for patients with TNBC.
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http://dx.doi.org/10.3389/fonc.2022.941283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300844PMC
July 2022

Engineering exposed vertical nano-TiO (001) facets/BiOI nanosheet heterojunction film for constructing a satisfactory PEC glucose oxidase biosensor.

RSC Adv 2022 Jun 5;12(30):19495-19504. Epub 2022 Jul 5.

State Key Laboratory of Marine Resource Utilization in South China Sea, College of Materials Science and Engineering, Hainan University Haikou 570228 China

In the field of photoelectrochemical (PEC) enzyme biosensors, constructing efficient photoelectrodes, in which the recombination of photogenerated carriers is an important factor affecting the performance, is of great significance. Herein, to enhance the separation efficiency of photogenerated carriers, titanium dioxide (TiO) nanosheet (NS)/bismuth oxyiodide (BiOI) NS/glucose oxidase (GOx) composites were prepared hydrothermal and solvothermal methods. Single-crystal anatase TiO NSs with a high percentage of (001) facets lead to better photocarrier separation due to heterojunctions between facets. After coupling with BiOI NSs, the photoelectrochemical performance of the electrode was greatly improved. The photogenerated electrons from TiO and BiOI gathered at TiO (101) and were exported through the fluorine-doped tin oxide (FTO) substrate to generate electrical signals. Photogenerated holes were transferred to TiO (001) and BiOI to participate in the enzymatic reaction, showing the outstanding separation of electrons and holes. The prepared TiO NS/BiOI NS/GOx glucose biosensor achieved satisfactory results, with sensitivity of 14.25 μA mM cm, a linear measurement range of 0-1 mM, and a limit of detection (3S/N) of 0.01 mM in phosphate buffered saline (PBS) at a pH of 7.4. The mechanism for the efficient separation of photogenerated carriers based on the facet heterojunctions introduced in this paper also provides new insights into other optoelectronic biosensors.
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http://dx.doi.org/10.1039/d2ra03070eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255561PMC
June 2022

TBX3 stimulates proliferation and stem cell self-renewal in bladder carcinoma.

Histol Histopathol 2022 Jul 20:18496. Epub 2022 Jul 20.

Department of Central Sterile Supply, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai City, Zhejiang Province, China.

Background: With the change of people's lifestyle in recent years, bladder carcinoma has been the second leading cause of death for men. Nevertheless, surgical results of bladder carcinoma are unsatisfying with recurrence and distant metastasis. Therefore, it is urgent to find a new target for bladder carcinoma treatment.

Methods: The protein and mRNA expression levels of TBX3 in bladder carcinoma tissue samples and cells were tested using western blot and qRT-PCR assays, respectively. Cancer stem cells (CSCs) were separated with immunomagnetic beads. Expression levels of cell stemness-associated proteins CD44, CD24 and ESA in T24 CSCs and T24 cells were detected by western blot assay. Cell self-renewal ability was detected by stem cell sphere formation assay. CCK-8 and colony formation assays examined cell viability and proliferation. Cell apoptotic level was examined by flow cytometry.

Results: Elevated TBX3 expression in bladder carcinoma stimulated cell proliferation and inhibited cell apoptosis. Stemness-related proteins and TBX3 were highly expressed in T24 CSCs relative to those in normal bladder carcinoma cells. In addition, TBX3 promoted stem cell self-renewal and inhibited cell apoptosis. Finally, qRT-PCR, western blot and cell sphere formation assays revealed that the potential role of TGF-β1 in the regulation of TBX3.

Conclusion: TBX3, mediated by TGF-β1, can promote bladder carcinoma cell proliferation, inhibit apoptosis, and enhance cell stemness. Hence, TBX3 is a potential target to stem cells of bladder carcinoma.
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http://dx.doi.org/10.14670/HH-18-496DOI Listing
July 2022

Enhanced fractional order sliding mode control for a class of fractional order uncertain systems with multiple mismatched disturbances.

ISA Trans 2022 Jul 7. Epub 2022 Jul 7.

School of Mechatronic Engineering and Automation, Foshan University, 33 Guangyun Road, Foshan, China.

To improve the control performance of the fractional order uncertain systems with multiple mismatched disturbances, an enhanced fractional order sliding mode control (FOSMC) method is developed in this paper. The multiple disturbances and uncertainties are estimated by the finite-time disturbance observers (FTDO) and a fractional order extended state observer (FOESO), respectively. A fractional order switching law is designed to provide a fast convergence mode for the system states. Then a novel FOSMC law is developed by incorporating the feedforward compensation, the fractional order switching law, and the auxiliary state for input saturation. The proposed method is applied to numerical examples and to a motor speed control problem. The effectiveness of the proposed method is demonstrated by the performance comparisons with some existing control methods.
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http://dx.doi.org/10.1016/j.isatra.2022.07.002DOI Listing
July 2022

Mediation of the APOE Associations With Cognition Through Cerebral Blood Flow: The CIBL Study.

Front Aging Neurosci 2022 30;14:928925. Epub 2022 Jun 30.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: The ε4 allele of the apolipoprotein E (APOE) gene is a strong genetic risk factor for aging-related cognitive decline. However, the causal connection between ε4 alleles and cognition is not well understood. The objective of this study was to identify the roles of cerebral blood flow (CBF) in cognitive-related brain areas in mediating the associations of APOE with cognition.

Methods: The multiple linear regression analyses were conducted on 369 subjects (mean age of 68.8 years; 62.9% of women; 29.3% of APOE ε4 allele carriers). Causal mediation analyses with 5,000 bootstrapped iterations were conducted to explore the mediation effects.

Result: APOE ε4 allele was negatively associated with cognition ( < 0.05) and CBF in the amygdala, hippocampus, middle temporal gyrus, posterior cingulate, and precuneus (all < 0.05). The effect of the APOE genotype on cognition was partly mediated by the above CBF (all < 0.05).

Conclusion: CBF partially mediates the potential links between APOE genotype and cognition. Overall, the APOE ε4 allele may lead to a dysregulation of the vascular structure and function with reduced cerebral perfusion, which in turn leads to cognitive impairment.
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http://dx.doi.org/10.3389/fnagi.2022.928925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279129PMC
June 2022

Prohibitins: A Key Link between Mitochondria and Nervous System Diseases.

Oxid Med Cell Longev 2022 8;2022:7494863. Epub 2022 Jul 8.

School of Medicine, Yangzhou University, Yangzhou 225001, China.

Prohibitins (PHBs) are conserved proteins in eukaryotic cells, which are mainly located in the inner mitochondrial membrane (IMM), cell nucleus, and cell membrane. PHBs play crucial roles in various cellular functions, including the cell cycle regulation, tumor suppression, immunoglobulin M receptor binding, and aging. In addition, recent in vitro and in vivo studies have revealed that PHBs are important in nervous system diseases. PHBs can prevent apoptosis, inflammation, mitochondrial dysfunction, and autophagy in neurological disorders through different molecules and pathways, such as OPA-1, PINK1/Parkin, IL6/STAT3, Tau, NO, LC3, and TDP43. Therefore, PHBs show great promise in the protection of neurological disorders. This review summarizes the relevant studies on the relationship between PHBs and neurological disorders and provides an update on the molecular mechanisms of PHBs in nervous system diseases.
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http://dx.doi.org/10.1155/2022/7494863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286927PMC
July 2022

EIS biosensor based on a novel Myoviridae bacteriophage SEP37 for rapid and specific detection of Salmonella in food matrixes.

Food Res Int 2022 Aug 17;158:111479. Epub 2022 Jun 17.

Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Wuhan 430070, China; College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Recently, using bacteriophages as new molecular probes in reliable platforms for the detection of bacterial pathogens has attracted more and more increasing attentions. In this paper, a novel isolated Myoviridae bacteriophage SEP37 was covalently immobilized onto gold nanoparticles (AuNPs) modified gold disk electrode (GDE) surfaces using cysteamine (Cys) as a crosslinker. Substrates of GDE-AuNPs-Cys-Phage SEP37 and specific capture of Salmonella cells had been characterized using scanning electron microscopy (SEM) separately. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to study the electrochemical response of the biosensor interface manufacturing and bacterial capture process. Under the optimal experimental conditions, this phage-based EIS biosensor was able to detect Salmonella with a wide linear range from 2 × 10 to 2 × 10 colony forming unit (CFU)/mL within 30 min in spiked lake water and lettuce samples, with a limit of detection (LOD) of 17 CFU/mL. The detection linear range of spiked chicken samples was 2 × 10 to 2 × 10 CFU/mL, with a LOD of 1.3 × 10 CFU/mL. In combination with a pre-enrichment process for 3.5 h, this assay could reach a LOD of 1 CFU/mL in chicken breast meat samples. Besides, this phage-based EIS biosensor provided good reproducibility and stability. This phage-based EIS biosensor opens a new opportunity for the detection of pathogenic bacteria using the inherent selectivity of bacteriophage recognition.
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http://dx.doi.org/10.1016/j.foodres.2022.111479DOI Listing
August 2022

Effects of thermal cycling on mechanical and antibacterial durability of bioactive low-shrinkage-stress nanocomposite.

J Dent 2022 Jul 8;124:104218. Epub 2022 Jul 8.

Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address:

Objectives: Recent studies developed low-shrinkage-stress composite with remineralizing and antibacterial properties to combat secondary caries and increase restoration longevity. However, their long-term durability in thermal cycling is unclear. The objectives of this study were to develop an antibacterial, remineralizing and low-shrinkage-stress composite, and to investigate its durability in thermal cycling for 20,000 cycles, equivalent to two years of clinical life.

Methods: The resin consisted of urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE). Composites were made with 5% dimethylaminohexadecyl methacrylate (DMAHDM) and 20% of nanoparticles of amorphous calcium phosphate (NACP). Composites were thermal cycled at 5°C and 55°C for 20,000 cycles. A human salivary biofilm model was used to evaluate antibiofilm activity before and after thermal cycling.

Results: After 20,000 cycles, the flexural strength of bioactive low-shrinkage-stress composite matched commercial control with no antibacterial activity (p > 0.05). Surface roughness was clinically acceptable at less than 0.2 μm. UV+NACP+DMAHDM composite reduced the total microorganisms, total streptococci, and mutans streptococci by 2-5 logs, compared to commercial composite. Biofilm lactic acid production was reduced by 11 folds. The antibacterial performance was maintained after thermal cycling, with no decrease after 20,000 cycles.

Conclusions: Bioactive low-shrinkage-stress composite possessed good mechanical properties that matched commercial composite both before and after thermal cycling. The new composite had potent antibacterial activity, which was maintained and did not decrease after thermal cycling.

Clinical Significance: The new bioactive low-shrinkage-stress composite could reduce polymerization shrinkage stress and release calcium and phosphate ions, with good mechanical properties and strong antibacterial function that were durable after thermal cycling. These properties indicate great potential for inhibiting recurrent caries and increasing the restoration longevity.
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http://dx.doi.org/10.1016/j.jdent.2022.104218DOI Listing
July 2022

Efficacy and safety of intravenous daratumumab-based treatments for AL amyloidosis: a systematic review and meta-analysis.

Cancer Cell Int 2022 Jul 4;22(1):222. Epub 2022 Jul 4.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng, Beijing, 100730, China.

Background: Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered with DARA IV have not been aggregated. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of DARA IV for AL amyloidosis.

Methods: We searched Medline, EMBASE, Cochrane Library and Web of Science up to 17 June 2021. Response rates and survival rates, and the corresponding 95% confidence intervals (CIs) were pooled and calculated using a fixed-effects model.

Results: Thirty studies (5 cohort studies and 25 single-arm studies) with 997 patients were included. In patients receiving DARA IV-based treatments, very good partial response or better response rate, complete response rate, very good partial response rate, partial response rate and overall response rate were 66% (95% CI, 62-69%), 30% (95% CI, 23-36%), 40% (95% CI, 33-46%), 17% (95% CI, 14-21%), and 77% (95% CI, 73-80%), respectively. Cardiac and renal responses were 41% (95% CI, 34-49%) and 43% (95% CI, 32-54%), respectively. 58% (95% CI, 49-66%) of patients achieved PFS one year or longer. 2.5% (range, 1-10.0%) of patients experienced grade 3 or 4 adverse events, of which the most common adverse event was lymphocytopenia (range, 13.6-25.0%).

Conclusion: This study supports the efficacy and safety of DARA IV for the treatment of patients with AL amyloidosis.
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http://dx.doi.org/10.1186/s12935-022-02635-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251945PMC
July 2022

[Heterogeneity and function of uterine NK cells: A review].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 Jul;38(7):657-660

Department of Obstetrics and Gynecology, Tangdu Hospital, the Air Force Medical University, Xi'an 710038, China. *Corresponding author, E-mail:

Natural killer (NK) cells present in large quantities, accounting for 70% of the maternal immune cells during the first trimester of pregnancy. With the development of single-cell sequencing technology, the researchers identified three groups of uterus NK cells with different phenotypes and functions in human uterus. decidual NK1 (dNK1) subsets produce growth promoting factors which regulate T helper type 2(Th2)cell immunity and thus facilitate pregnancy. dNK2 and dNK3 subsets secrete inflammatory cytokines that are regulators of Th2 cell immunity, not conductive to establishing and maintaining pregnancy. Single-cell sequencing studies in mice revealed a new subset of uNK (CYP26A1uNK) cells that play an important role in embryo implantation and immune regulation.
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July 2022

l-Ergothioneine Exhibits Protective Effects against Dextran Sulfate Sodium-Induced Colitis in Mice.

ACS Omega 2022 Jun 14;7(25):21554-21565. Epub 2022 Jun 14.

Department of Nutrition and Food Hygiene, School of Public Health, Shenyang Medical College, Shenyang 110034, China.

: Ulcerative colitis (UC) is a chronic disease of the intestinal tract in which excessive activation of inflammatory response is correlated. l-Ergothioneine (EGT) widely existing in mushrooms has various physiological activities. In this study, the protective effects of EGT on dextran sulfate sodium (DSS)-induced colitis mice were investigated. : It was observed that EGT administration, especially at the high dose level, prevented the body weight loss, the colon shortening, and the increase in disease activity index and spleen index caused by DSS. Moreover, EGT supplementation attenuated DSS-induced gut barrier damage by enhancing the expression of tight-junction protein and recovering the loss of gut mucus layer. Furthermore, EGT considerably decreased the colonic myeloperoxidase (MPO) activity induced by DSS, but no significant differences were observed in the concentrations of IL-6 and TNF-α in colon tissues. Additionally, EGT downregulated the populations of CD4 T cells and macrophages, indicating that EGT stabilized the immune response caused by DSS. : Together these results suggest that EGT can alleviate DSS-induced colitis and provide important insights concerning the potential anticolitis activity of such food products.
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http://dx.doi.org/10.1021/acsomega.2c01350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245115PMC
June 2022

The effect of ovarian stimulation on aneuploidy of early aborted tissues and preimplantation blastocysts: comparison of the GnRH agonist long protocol with the GnRH antagonist protocol.

J Assist Reprod Genet 2022 Jun 29. Epub 2022 Jun 29.

Center for Reproductive Medicine, Department of Gynecology & Obsterics, Tang Du Hospital, the Air Force Military Medical University, Xi'an, Shaan xi, People's Republic of China.

Purpose: To compare aneuploidy rates in early aborted tissues or blastocysts between in vitro fertilization (IVF) cycles after the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol or the GnRH agonist (GnRH-a) long protocol.

Methods: This was a retrospective cohort study from a university-affiliated fertility center. In total, 550 early miscarriage patients who conceived through IVF/intracytoplasmic sperm injection (ICSI) after receiving the GnRH-ant or GnRH-a long protocol were analyzed to compare aneuploidy rates in early aborted tissues. To compare aneuploidy rates in blastocysts, 404 preimplantation genetic testing for aneuploidy (PGT-A) cycles with the GnRH-ant protocol or GnRH-a long protocol were also analyzed.

Results: For early miscarriage patients who conceived through IVF/ICSI, compared to the GnRH-a long protocol group, the GnRH-ant protocol group had a significantly higher rate of aneuploidy in early aborted tissues (48.51% vs. 64.19%). Regarding PGT-A cycles, the rate of blastocyst aneuploidy was significantly higher in the GnRH-ant protocol group than the GnRH-a long protocol group (39.69% vs. 52.27%). After stratification and multiple linear regression, the GnRH-ant regimen remained significantly associated with an increased risk of aneuploidy in early aborted tissues and blastocysts [OR (95% CI) 1.81 (1.21, 2.71), OR (95% CI) 1.65 (1.13, 2.42)]. Furthermore, the blastocyst aneuploidy rate in the GnRH-ant protocol group was significantly higher but only in young and normal ovarian responders [OR (95% CI) 5.07 (1.99, 12.92)].

Conclusion: Compared to the GnRH-a long protocol, the GnRH-ant protocol is associated with a higher aneuploidy rate in early aborted tissues and blastocysts. These results should be confirmed in a multicenter, randomized controlled trial.
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http://dx.doi.org/10.1007/s10815-022-02557-2DOI Listing
June 2022

PGT-A: The biology and hidden failures of randomized control trials.

Prenat Diagn 2022 Jun 28. Epub 2022 Jun 28.

Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.

Objective: Preimplantation Genetic Testing - Aneuploidy (PGT-A) for embryo selection has undergone significant advancements in the last 2 decades and yet many studies still fail to demonstrate any clinical benefits over traditional embryo morphology selection (Mo-S). To understand this conundrum, we performed a multi-center clinical study of PGT-A patients, where Mo-S and euploid selection (Eu-S) outcomes were directly compared.

Method: All suitable blastocysts were biopsied and analyzed for chromosome copy number. Outcomes (positive beta hCG, implantation, ongoing pregnancy, and live birth rates) for Eu-S were compared to Mo-S using single embryo transfers.

Results: Compared to Eu-S embryos, Mo-S embryos resulted in significant reduction of outcomes for positive beta hCG (p = 0.0005), implantation (p = 0.0008), ongoing pregnancy (p = 0.0046), livebirth (p = 0.0112), babies per transfer (p = 0.0112), and babies per embryo transferred (p = 0.0112). Morphology selection resulted in patients of all age groups having non-euploid embryos chosen for transfer. Post-hoc evaluation of individual clinic performances showed variable transfer outcomes that could potentially confound the true benefits of PGT-A.

Conclusion: Embryo chromosome status is central to improved embryo transfer outcomes and sole reliance on current morphology-based selection practices, without Eu-S, will always compromise outcomes. Often overlooked but a major effector of successful PGT-A outcomes are individual clinic performances.
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http://dx.doi.org/10.1002/pd.6199DOI Listing
June 2022

Chitosan-based composite microspheres for treatment of hexavalent chromium and EBBR from aqueous solution.

Chemosphere 2022 Oct 25;305:135486. Epub 2022 Jun 25.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu, 212013, China. Electronic address:

Hexavalent chromium is widely used in industrial fields, but its pollution has posed a great threat to the environment due to its high toxicity. We created a chitosan-based microsphere biosorbent (CP) by combining polyethyleneimine with chitosan adopting inverse emulsion polymerization method. Under the optimal conditions (pH = 3), the maximum adsorption capacity of composite microspheres can reach 299.89 mg g, which is much higher than that of chitosan microspheres (168.91 mg g). When the amount of CP is 0.25 g L, the removal rate of 50 mg L Cr(VI) and 50 mg L Eriochrome blue-black R (EBBR) can reach 95% and 99%, respectively. The time required for CP to reach adsorption equilibrium (180 min) was significantly shorter than that of chitosan microspheres (540 min), and the adsorption rate was significantly improved. Langmuir isotherm model, pseudo-second-order kinetic model and thermodynamic calculation results penetrated an endothermic spontaneous, monolayer, and chemical adsorption process. Biomass composite microspheres CP has obvious selectivity and the adsorption capacity retention rate of CP was still 71.32% after four adsorption cycles. This work proposed an easily prepared and biomass-based microspheres for the effective removal of Cr(VI) in printing and dyeing wastewater pollution through adsorption.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135486DOI Listing
October 2022

Loss of Lipocalin 10 Exacerbates Diabetes-Induced Cardiomyopathy Disruption of Nr4a1-Mediated Anti-Inflammatory Response in Macrophages.

Front Immunol 2022 10;13:930397. Epub 2022 Jun 10.

Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

Metabolic disorders (i.e., hyperglycemia, hyperlipidemia, and hyperinsulinemia) cause increased secretion of inflammatory cytokines/chemokines, leading to gradual loss of cardiac resident macrophage population and increased accumulation of inflammatory monocytes/macrophages in the heart. Such self-perpetuating effect may contribute to the development of cardiomyopathy during diabetes. Recent meta-analysis data reveal that lipocalin 10 (Lcn10) is significantly downregulated in cardiac tissue of patients with heart failure but is increased in the blood of septic patients. However, the functional role of Lcn10 in cardiac inflammation triggered by metabolic disorders has never been investigated. In this study, we demonstrate that the expression of Lcn10 in macrophages was significantly decreased under multiple metabolic stress conditions. Furthermore, Lcn10-null macrophages exhibited pro-inflammatory phenotype in response to inflammation stimuli. Next, using a global Lcn10-knockout (KO) mouse model to induce type-2 diabetes (T2D), we observed that loss of Lcn10 promoted more pro-inflammatory macrophage infiltration into the heart, compared to controls, leading to aggravated insulin resistance and impaired cardiac function. Similarly, adoptive transfer of Lcn10-KO bone marrow cells into X-ray irradiated mice displayed higher ratio of pro-/anti-inflammatory macrophages in the heart and worsened cardiac function than those mice received wild-type (WT) bone marrows upon T2D conditions. Mechanistically, RNA-sequencing analysis showed that Nr4a1, a nuclear receptor known to have potent anti-inflammatory effects, is involved in Lcn10-mediated macrophage activation. Indeed, we found that nuclear translocation of Nr4a1 was disrupted in Lcn10-KO macrophages upon stimulation with LPS + IFNγ. Accordingly, treatment with Cytosporone B (CsnB), an agonist of Nr4a1, attenuated the pro-inflammatory response in Lcn10-null macrophages and partially improved cardiac function in Lcn10-KO diabetic mice. Together, these findings indicate that loss of Lcn10 skews macrophage polarization to pro-inflammatory phenotype and aggravates cardiac dysfunction during type-2 diabetes through the disruption of Nr4a1-mediated anti-inflammatory signaling pathway in macrophages. Therefore, reduction of Lcn10 expression observed in diabetic macrophages may be responsible for the pathogenesis of diabetes-induced cardiac dysfunction. It suggests that Lcn10 might be a potential therapeutic factor for diabetic heart failure.
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http://dx.doi.org/10.3389/fimmu.2022.930397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226549PMC
June 2022

Novel low-shrinkage-stress bioactive nanocomposite with anti-biofilm and remineralization capabilities to inhibit caries.

J Dent Sci 2022 Apr 14;17(2):811-821. Epub 2021 Oct 14.

Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, USA.

Background/purpose: A common reason for dental composite restoration failure is recurrent caries at the margins. Our objectives were to: (1) develop a novel low-shrinkage-stress, antibacterial and remineralizing resin composite; (2) evaluate the effects of dimethylaminohexadecyl methacrylate (DMAHDM) on mechanical properties, biofilm inhibition, calcium (Ca) and phosphate (P) ion release, degree of conversion, and shrinkage stress on the new low-shrinkage-stress resin composite for the first time.

Material And Methods: The resin consisted of urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE) with high resistance to salivary hydrolytic degradation. Composites were made with 0%-8% of DMAHDM for antibacterial activity, and 20% of nanoparticles of amorphous calcium phosphate (NACP) for remineralization. Mechanical properties and biofilm growth on composites were assessed. Ca and P ion releases, degree of conversion and shrinkage stress were evaluated.

Results: Adding 2-5% DMAHDM and 20% NACP into the low-shrinkage-stress composite did not compromise the mechanical properties (p > 0.05). The incorporation of DMAHDM greatly reduced biofilm colony-forming units by 2-5 log and lactic acid production by 7 folds, compared to a commercial composite (p < 0.05). Adding 5% DMAHDM did not compromise the Ca and P ion release. The low-shrinkage-stress composite maintained a high degree of conversion of approximately 70%, while reducing the shrinkage stress by 37%, compared to a commercial control (p < 0.05).

Conclusion: The bioactive low-shrinkage-stress composite reduced the polymerization shrinkage stress, without compromising other properties. Increasing the DMAHDM content increased the antibacterial effect in a dose-dependent manner.
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http://dx.doi.org/10.1016/j.jds.2021.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201927PMC
April 2022

Metal- and base-free tandem sulfonylation/cyclization of 1,5-dienes with aryldiazonium salts the insertion of sulfur dioxide.

RSC Adv 2022 Jun 6;12(26):16745-16750. Epub 2022 Jun 6.

Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, West China School of Pharmacy, Sichuan University Chengdu 610041 China

A metal- and base-free 5--trig sulfonylative cyclization between 1,5-dienes, aryldiazonium salts and SO (from SOgen) is presented. This method could successfully produce sulfonylated pyrrolin-2-ones in one pot with excellent regioselectivity and good-to-excellent yields. This strategy features mild reaction conditions and broad substrate scope. Moreover, a scale-up reaction and three synthetic applications demonstrate the practicality of this method. Lastly, control experiments indicate that the 5--trig sulfonylative cyclization may proceed in a radical pathway.
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http://dx.doi.org/10.1039/d2ra03034aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170380PMC
June 2022

[Villi exosomes deliver HLA-G to enhance the expression of osteoglycin and pleiotrophin in decidual NK cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 Jun;38(6):535-541

Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China. *Corresponding author, E-mail:

Objective To identify the effect of HLA-G-containing exosomes on the secretory function of growth-promoting factors osteoglycin (OGN) and pleiotrophin (PTN) by decidual NK (dNK) cells. Methods dNK cells were co-cultured with HLA-G-containing exosomes from the villi of patients undergoing unexplained recurrent pregnancy loss (uRPL) and normal induced abortion, respectively. Sequentially, OGN and PTN of the dNK cells were determined using real time quantitative PCR and western blotting. Exosomes overexpressing HLA-G (HLA-G-EXO) were obtained by transfecting the villous trophoblast cell line HTR-8/Svneo with lentivirus LV-HLA-G. dNK cells were further co-cultured with HLA-G-EXO for detecting the expression of OGN and PTN, the culture supernatant of which was used to treat HTR-8/Svneo cells, and the proliferation of HTR-8/Svneo cells was detected by the CCK-8 assay. Results Exosomes derived from villi of patients receiving normal induced abortion significantly enhanced the expression of OGN and PTN in dNK cells compared with those from patients of the uRPL group. Besides, HLA-G-EXO markedly enhanced the expression of OGN and PTN in dNK cells. The culture supernatant of HLA-G-EXO treated dNK cells could promote the proliferation of HTR-8/Svneo cells. Conclusion Villi-derived HLA-G containing exosomes may enhance the secretion of growth-promoting factors in dNK cells.
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June 2022

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

Mol Ecol Resour 2022 Jun 20. Epub 2022 Jun 20.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.
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http://dx.doi.org/10.1111/1755-0998.13669DOI Listing
June 2022

Two Novel Intronic Mutations in the Gene in Two Families With CSF1R-Microglial Encephalopathy.

Front Cell Dev Biol 2022 24;10:902067. Epub 2022 May 24.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

To describe two novel heterozygous splicing variants of the gene responsible for CSF1R-microglial encephalopathy in two unrelated Han Chinese families and further explore the relationship between the pathological and neuroimaging findings in this disease. The demographic data, detailed medical history, and clinical manifestations of two unrelated Han families with CSF1R-microglial encephalopathy were recorded. Some family members also underwent detailed neuropsychological evaluation, neuroimaging, and genetic testing. The probands underwent whole-exome sequencing (WES) or next-generation sequencing (NGS) to confirm the diagnosis. The findings were substantiated using Sanger sequencing, segregation analysis, and phenotypic reevaluation. Both families presented with a dominant hereditary pattern. Five of 27 individuals (four generations) from the first family, including the proband and his sister, father, uncle, and grandmother, presented with cognitive impairments clinically during their respective lifetimes. Brain magnetic resonance imaging (MRI) depicted symmetric, confluent, and diffuse deep white matter changes, atrophy of the frontoparietal lobes, and thinning of the corpus callosum. The proband's brother remained asymptomatic; brain MRI revealed minimal white matter changes, but pseudo-continuous arterial spin labeling (pCASL) demonstrated a marked reduction in the cerebral blood flow (CBF) in the bilateral deep white matter and corpus callosum. Seven family members underwent WES, which identified a novel splice-site heterozygous mutation (c.2319+1C>A) in intron 20 of the gene in four members. The proband from the second family presented with significant cognitive impairment and indifference; brain MRI depicted symmetric diffuse deep white matter changes and thinning of the corpus callosum. The proband's mother reported herself to be asymptomatic, while neuropsychological evaluation suggested mild cognitive impairment, and brain MRI demonstrated abnormal signals in the bilateral deep white matter and corpus callosum. NGS of 55 genes related to hereditary leukodystrophy was performed for three members, which confirmed a novel splice-site heterozygous mutation (c.1858+5G>A) in intron 13 of the gene in two members. Our study identified two novel splicing mutation sites in the gene within two independent Chinese families with CSF1R-microglial encephalopathy, broadening the genetic spectrum of CSF1R-microglial encephalopathy and emphasizing the value of pCASL for early detection of this disease.
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http://dx.doi.org/10.3389/fcell.2022.902067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198639PMC
May 2022

Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells.

Invest Ophthalmol Vis Sci 2022 06;63(6):16

Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.

Purpose: The purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells.

Methods: The expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay.

Results: ACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme.

Conclusions: In this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.
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http://dx.doi.org/10.1167/iovs.63.6.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206495PMC
June 2022

Polyphosphate in Antiviral Protection: A Polyanionic Inorganic Polymer in the Fight Against Coronavirus SARS-CoV-2 Infection.

Prog Mol Subcell Biol 2022 ;61:145-189

ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Polyanions as polymers carrying multiple negative charges have been extensively studied with regard to their potential antiviral activity. Most studies to date focused on organic polyanionic polymers, both natural and synthetic. The inorganic polymer, polyphosphate (polyP), despite the ubiquitous presence of this molecule from bacteria to man, has attracted much less attention. More recently, and accelerated by the search for potential antiviral agents in the fight against the pandemic caused by the coronavirus SARS-CoV-2, it turned out that polyP disrupts the first step of the viral replication cycle, the interaction of the proteins in the virus envelope and in the cell membrane that are involved in the docking process of the virus with the target host cell. Experiments on a molecular level using the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the cellular angiotensin converting enzyme 2 (ACE2) receptor revealed that polyP strongly inhibits the binding reaction through an electrostatic interaction between the negatively charged centers of the polyP molecule and a cationic groove, which is formed by positively charged amino acids on the RBD surface. In addition, it was found that polyP, due to its morphogenetic and energy delivering activities, enhances the antiviral host innate immunity defense of the respiratory epithelium. The underlying mechanisms and envisaged application of polyP in the therapy and prevention of COVID-19 are discussed.
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http://dx.doi.org/10.1007/978-3-031-01237-2_7DOI Listing
June 2022

Biomimetic Polyphosphate Materials: Toward Application in Regenerative Medicine.

Prog Mol Subcell Biol 2022 ;61:83-130

ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

In recent years, inorganic polyphosphate (polyP) has attracted increasing attention as a biomedical polymer or biomaterial with a great potential for application in regenerative medicine, in particular in the fields of tissue engineering and repair. The interest in polyP is based on two properties of this physiological polymer that make polyP stand out from other polymers: polyP has morphogenetic activity by inducing cell differentiation through specific gene expression, and it functions as an energy store and donor of metabolic energy, especially in the extracellular matrix or in the extracellular space. No other biopolymer applicable in tissue regeneration/repair is known that is endowed with this combination of properties. In addition, polyP can be fabricated both in the form of a biologically active coacervate and as biomimetic amorphous polyP nano/microparticles, which are stable and are activated by transformation into the coacervate phase after contact with protein/body fluids. PolyP can be used in the form of various metal salts and in combination with various hydrogel-forming polymers, whereby (even printable) hybrid materials with defined porosities and mechanical and biological properties can be produced, which can even be loaded with cells for 3D cell printing or with drugs and support the growth and differentiation of (stem) cells as well as cell migration/microvascularization. Potential applications in therapy of bone, cartilage and eye disorders/injuries and wound healing are summarized and possible mechanisms are discussed.
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http://dx.doi.org/10.1007/978-3-031-01237-2_5DOI Listing
June 2022

Polyphosphate in Chronic Wound Healing: Restoration of Impaired Metabolic Energy State.

Prog Mol Subcell Biol 2022 ;61:51-82

ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Many pathological conditions are characterized by a deficiency of metabolic energy. A prominent example is nonhealing or difficult-to-heal chronic wounds. Because of their unique ability to serve as a source of metabolic energy, inorganic polyphosphates (polyP) offer the opportunity to develop novel strategies to treat such wounds. The basis is the generation of ATP from the polymer through the joint action of two extracellular or plasma membrane-bound enzymes alkaline phosphatase and adenylate kinase, which enable the transfer of energy-rich phosphate from polyP to AMP with the formation of ADP and finally ATP. Building on these findings, it was possible to develop novel regeneratively active materials for wound therapy, which have already been successfully evaluated in first studies on patients.
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http://dx.doi.org/10.1007/978-3-031-01237-2_4DOI Listing
June 2022

Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B.

JAMA Netw Open 2022 06 1;5(6):e2216485. Epub 2022 Jun 1.

Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

Importance: Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) constitutes an atypical serological profile in chronic hepatitis B virus infection, and the association between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) remains unclear.

Objective: To investigate the association of coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with CHB.

Design, Setting, And Participants: Consecutive treatment-naive patients with CHB from 2 medical institutions in China were enrolled between January 10, 2015, and March 31, 2021. Severe liver fibrosis and cirrhosis were identified using the aspartate transaminase (AST) to platelet ratio index (APRI), the fibrosis index based on 4 factors (FIB-4; factors comprise age, AST level, alanine aminotransferase [ALT] level, and platelet count), transient elastography, or ultrasonography. Data were analyzed from August 1, 2021, to April 15, 2022.

Main Outcomes And Measures: The primary outcomes were rates of severe liver fibrosis and cirrhosis among patients with vs patients without coexistant HBsAg and anti-HBs. Severe liver fibrosis was defined as an APRI score of 1.5 or higher, a FIB-4 score of 3.25 or higher, or a liver stiffness measurement of 8 kPa or higher; cirrhosis was defined as an APRI score of 2.0 or higher, a FIB-4 score of 6.5 or higher, a liver stiffness measurement of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis.

Results: Of 6534 enrolled patients, 4033 patients (61.7%) were male, and the median (IQR) age was 41.0 (33.0-52.0) years. A total of 277 patients (4.2%) had coexistent HBsAg and anti-HBs. Patients with vs without anti-HBs were older (median [IQR], 46.0 [33.0-55.5] years vs 41.0 [33.0-52.0] years) and had a higher proportion of hepatitis B e antigen (HBeAg) positivity (123 of 277 patients [44.4%] vs 2115 of 6257 patients [33.8%]; P < .001), higher ALT levels (median [IQR], 45.1 [24.6-119.0] U/L vs 36.7 [22.0-77.0] U/L; P = .001) and AST levels (median [IQR], 35.0 [23.5-68.4] U/L vs 28.3 [21.6-51.0] U/L; P < .001), and lower platelet counts (median [IQR], 173.0 × 103/μL [129.0-212.5 × 103/μL] vs 185.0 × 103/μL [141.0-224.0 × 103/μL]; P = .004), albumin levels (median [IQR], 4.37 [4.11-4.56] g/dL vs 4.43 [4.17-4.61] g/dL; P = .02), and HBsAg levels (median [IQR], 2.8 log10 [1.6-3.4 log10] IU/mL vs 3.3 log10 [2.6-3.9 log10] IU/mL; P < .001). Compared with patients without anti-HBs, those with anti-HBs had higher APRI scores (median [IQR], 0.5 [0.3-1.4] vs 0.4 [0.3-0.9]; P < .001), FIB-4 scores (median [IQR], 1.4 [0.9-2.6] vs 1.1 [0.7-2.1]; P < .001), and liver stiffness values (median [IQR], 7.5 [6.2-9.8] kPa vs 6.3 [5.2-8.1] kPa; P = .003). Patients with anti-HBs also had higher proportions of severe liver fibrosis (102 of 277 patients [36.8%] vs 1397 of 6207 patients [22.5%]; P < .001) and cirrhosis (87 of 277 patients [31.4%] vs 1194 of 6213 patients [19.2%]; P < .001) compared with patients without anti-HBs. The coexistence of HBsAg and anti-HBs was independently associated with severe liver fibrosis (odds ratio [OR], 2.29; 95% CI, 1.56-3.38; P < .001) and cirrhosis (OR, 1.73; 95% CI, 1.12-2.68; P = .01) in the multivariate analysis. However, the association of coexistent HBsAg and anti-HBs with cirrhosis was only observed in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in patients with HBeAg positivity (OR, 1.45; 95% CI, 0.87-2.43; P = .16).

Conclusions And Relevance: In this cross-sectional study, the coexistence of HBsAg and anti-HBs was unusual in hepatitis B virus infection and was associated with more advanced liver diseases, such as severe liver fibrosis and cirrhosis, especially among patients with HBeAg negativity. These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.16485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194671PMC
June 2022
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