Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report.

BACKGROUND: Fulminant type 1 diabetes mellitus (FT1DM) that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM (PF), always without history of abnormal glucose metabolism. Here, we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus (GDM). CASE SUMMARY: The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected, and the patients and their infants were followed up. All patients were diagnosed with GDM during the second trimester and were treated. The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM. Two patients had an insulin allergy, and two had symptoms of upper respiratory tract infection before onset. One patient developed ketoacidosis, and three developed ketosis. Two patients had cesarean section deliveries, and two had vaginal deliveries. The growth and development of the infants were normal. C-peptide levels were lower than those at onset, suggesting progressive impairment of islet function. The frequencies of the DRB1 09:01, DQB1 03: 03, DQA1 03:02, DPA1 01:03, DPA1 02:02, DPB1 05:01, DRB4 01:03, G 01:01, and G 01:04 human leukocyte antigen (HLA)-G alleles were high in the present study. CONCLUSION: In comparison with pregnancy-associated FT1DM (PF), patients with GDM combined with FT1DM had an older age of onset, higher body mass index, slower onset, fewer prodromal symptoms, and less acidosis. The pathogenesis may be due to various factors affecting the already fragile ß-cells of GDM patients with genetically susceptible class II HLA genotypes. We speculate that GDM combined with FT1DM during pregnancy, referred to as "double diabetes," is a subtype of PF with its own unique characteristics that should be investigated further.

Correction: MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer.

Correction for 'MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer' by Jie Liu et al., Biomater. Sci., 2022, 10, 4596-4611, https://doi.org/10.1039/D2BM00543C.

High-efficiency antibacterial calcium alginate/lysozyme/AgNPs composite sponge for wound healing.

Infection poses a significant barrier to effective wound repair, leading to increased inflammatory responses that ultimately result in incomplete and prolonged wound healing. To address this challenge, numerous antibacterial ingredients have been incorporated into dressings to inhibit wound infection. Our previous work demonstrated that lysozyme/silver nanoparticles (LYZ/AgNPs) complexes, prepared using an eco-friendly one-step aqueous method, exhibited excellent antibacterial efficacy with favorable biosafety. To further explore its potential application in advancing wound healing, calcium alginate (CA) with good porosity, water absorption, and water retention capacities was formulated with LYZ/AgNPs to prepare composite sponge (CA/LYZ/AgNPs). As expected, in vivo experiments involving full-thickness skin wound and scald wound healing experiments demonstrated that CA-LYZ-AgNPs composite sponges with excellent biocompatibility exhibited remarkable antibacterial activity against gram-positive bacteria, gram-negative bacteria and fungi, and outperformed the wound healing process efficacy of other commercially available AgNPs-loaded wound dressings. In summary, this work introduces a CA/LYZ/AgNPs sponge featuring exceptional antibacterial efficacy and biocompatibility, thus holding promising potential in wound care applications.

Complete genomic profiles of 1496 Taiwanese reveal curated medical insights.

INTRODUCTION: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population. OBJECTIVES: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population. METHODS: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw). RESULTS: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively. CONCLUSION: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.

Andrias Davidianus Mucus-Based Bioadhesive with Enhanced Adhesion and Wound Healing Properties.

The skin secretion of Andrias davidianus (SSAD) is a novel biological adhesive raw material under development. This material exhibits robust adhesion while maintaining the flexibility of the wound. It also has the potential for large-scale production, making it promising for practical application explore. Hence, in-depth research on methods to fine-tune SSAD properties is of great importance to promote its practical applications. Herein, we aim to enhance the adhesive and healing properties of SSAD by incorporating functional components. To achieve this goal, we selected 3,4-dihydroxy-l-phenylalanine and vaccarin as the functional components and mixed them with SSAD, resulting in a new bioadhesive, namely, a formulation termed "enhanced SSAD" (ESSAD). We found that the ESSAD exhibited superior adhesive properties, and its adhesive strength was improved compared with the SSAD. Moreover, ESSAD demonstrated a remarkable ability to promote wound healing. This study presents an SSAD-based bioadhesive formulation with enhanced properties, affirming the feasibility of developing SSAD-based adhesive materials with excellent performance and providing new evidence for the application of SSAD. This study also aims to show that SSAD can be mixed with other substances, and addition of effective components to SSAD can be studied to further adjust or improve its performance.

Magnetic Fields Reduce Apoptosis by Suppressing Phase Separation of Tau-441.

The biological effects of magnetic fields (MFs) have been a controversial issue. Fortunately, in recent years, there has been increasing evidence that MFs do affect biological systems. However, the physical mechanism remains unclear. Here, we show that MFs (16 T) reduce apoptosis in cell lines by inhibiting liquid-liquid phase separation (LLPS) of Tau-441, suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the "mysterious" magnetobiological effects. The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite. The phase-separated droplets of Tau-441 recruited hexokinase (HK), resulting in a decrease in the amount of free HK in the cytoplasm. In cells, HK and Bax compete to bind to the voltage-dependent anion channel (VDAC I) on the mitochondrial membrane. A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I, leading to increased Bax-mediated apoptosis. In the presence of a static MF, LLPS was marked inhibited and HK recruitment was reduced, resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I, thus reducing Bax-mediated apoptosis. Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS. In addition, these results show the potential applications of physical environments, such as MFs in this study, in the treatment of LLPS-related diseases.

Curcumin inhibits liquid-liquid phase separation of fused in sarcoma and attenuates the sequestration of pyruvate kinase to restore cellular metabolism.

The abnormal accumulation of fused in sarcoma (FUS) is a pathological hallmark in a proportion of patients with frontotemporal dementia and amyotrophic lateral sclerosis. Therefore, the clearance of FUS aggregates is a possible therapeutic strategy for FUS-associated neurodegenerative diseases. This study reports that curcumin can strongly suppress FUS droplet formation and stress granule aggregation of FUS. Fluorescence spectra and isothermal titration calorimetry showed that curcumin can bind FUS through hydrophobic interactions, thereby reducing the ß-sheet content of FUS. Aggregated FUS sequesters pyruvate kinase, leading to reduced ATP levels. However, results from a metabolomics study revealed that curcumin changed the metabolism pattern and differentially expressed metabolites were enriched in glycolysis. Curcumin attenuated FUS aggregation-mediated sequestration of pyruvate kinase and restored cellular metabolism, consequently increasing ATP levels. These results indicate that curcumin is a potent inhibitor of FUS liquid-liquid phase separation and provide novel insights into the effect of curcumin in ameliorating abnormal metabolism.

Microfluidic rotating-target device capable of three-degrees-of-freedom motion for efficient in situ serial synchrotron crystallography.

There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1 mg of protein is consumed in collecting a complete dataset.

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Antibacterial activity of lysozyme-loaded cream against MRSA and promotion of scalded wound healing.

Staphylococcus aureus (S. aureus) infection, especially its drug-resistant bacterial infection, is a great challenge often faced by clinicians and patients, and it is also one of the most important threats to public health. Finding a safe and effective antibacterial agent is of great significance for the prevention and treatment of S. aureus infection. Lysozyme is known to have antibacterial effects against Gram-positive bacteria including S. aureus. Here, high-quality lysozyme with a purity of more than 99% and an activity of more than 60, 000 U/mg was prepared from egg white, which showed excellent antibacterial activity against three strains of S. aureus, especially against MRSA. Furthermore, an antibacterial cream loaded with lysozyme was prepared and tested in scald wound healing. The lysozyme-loaded cream exhibited the effect of preventing wound infection and promoting wound healing on scalds, and no toxicity was found in animal organs. Overall, lysozyme showed great application potential in the prevention and treatment of infections caused by S. aureus and scalded wound healing. The most remarkable discovery in this work is the unexpectedly powerful inhibitory effect of lysozyme on the drug-resistant bacterial, especially MRSA, which is usually very difficult to deal with using normal antibacterial drugs.

MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer.

RNA interference is a promising way to treat cancer and the construction of a stable drug delivery system is critically important for its application. Gelatin nanospheres (GNs) comprise a biodegradable drug vehicle with excellent biocompatibility, but there are limited studies on its delivery and role in the stabilization of miRNA and siRNA. Breast cancer is the most diagnosed type of female cancer worldwide. Abnormal miRNA expression is closely related to the occurrence and progression of estrogen receptor-positive (ER+) breast cancer. In this study, miR-4458 was upregulated in ER+ breast cancer and could inhibit MCF-7 cell viability, colony formation, migration, and invasion. Collagen type XI alpha 1 (COL11A1) was identified as a directly interacting protein of miR-4458 and an important component of the extracellular matrix. High COL11A1 expression was positively correlated with poor prognosis, lower overall survival, disease-free survival, and a late tumor-node-metastasis stage. COL11A1 knockdown could inhibit MCF-7 cell migration and invasion. GNs were used to load a miR-4458 mimic or COL11A1 siRNA (si-COL11A1) to achieve sustained and controlled release in xenograft nude mice. Their tumor volume was decreased, tumor cell apoptosis was promoted, and hepatic metastasis was significantly inhibited. Moreover, the DDR2/SRC signaling pathway was inactivated after transfection with the miR-4458 mimic and si-COL11A1. In conclusion, GNs can be potentially used to deliver siRNA or miRNA, and miR-4458 and COL11A1 can be possible targets for ER+ breast cancer treatment.

miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Some microRNAs (miRNAs) were abnormally expressed in TNBC, and they are closely related to the occurrence and progression of TNBC. Here, we found that miR-506 was significantly downregulated in TNBC and relatively lower miR-506 expression predicted a poorer prognosis. Moreover, we found that miR-506 could inhibit MDA-MB-231 cell viability, colony formation, migration, and invasion, and suppress the ERK/Fos oncogenic signaling pathway through upregulating its direct target protein proenkephalin (PENK). Therefore, miR-506 was proposed as a nucleic acid drug for TNBC therapy. However, miRNA is unstable in vivo, which limiting its application as a therapeutic drug via conventional oral or injected therapies. Here, a gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA. Exogenous miR-506 mimic was loaded on GNs and injected into the in situ TNBC animal model, and the miR-506 could achieve sustained and controlled release. The results confirmed that overexpression of miR-506 and PENK in vivo through loading on GNs inhibited in situ triple-negative breast tumor growth and metastasis significantly in the xenograft model. Moreover, we indicated that the ERK/Fos signaling pathway was intensively inactivated after overexpression of miR-506 and PENK both in vitro and in vivo, which was further validated by the ERK1/2-specific inhibitor SCH772984. In conclusion, this study demonstrates that miR-506-loaded GNs have great potential in anti-TNBC aggressiveness therapy.

Searching for conditions of protein self-assembly by protein crystallization screening method.

The self-assembly of biomacromolecules is an extremely important process. It is potentially useful in the fields of life science and materials science. To carry out the study on the self-assembly of proteins, it is necessary to find out the suitable self-assembly conditions, which have always been a challenging task in practice. Inspired by the screening technique in the field of protein crystallization, we proposed using the same screening technique for seeking suitable protein self-assembly conditions. Based on this consideration, we selected 5 proteins (ß-lactoglobulin, hemoglobin, pepsin, lysozyme, α-chymotrypsinogen (II) A) together with 5 screening kits (IndexTM, BML, Morpheus, JCSG, PEG/Ion ScreenTM) to investigate the performance of these crystallization screening techniques in order to discover new optimized conditions of protein self-assembly. The screens were all kept at 293 K for certain days, and were analyzed using optical microscope, scanning electron microscope, transmission electron microscope, atomic force microscope, fluorescence microscope, and atomic absorption spectroscope. The results demonstrated that the method of protein crystallization screening can be successfully applied in the screening of self-assembly conditions. This method is fast, high throughput, and easily implemented in an automated system, with a low protein consumption feature. These results suggested that such strategy can be applied to finding new conditions or forms in routine research of protein self-assembly. KEY POINTS: • Protein crystallization screening method is successfully applied in the screening of self-assembly conditions. • This screening method can be applied on various kinds of proteins and possess a feature of low protein consumption. • This screening method is fast, high throughput, and easily implemented in an automated system.

Erratum to "The Possibility of Changing the Wettability of Material Surface by Adjusting Gravity".

[This corrects the article DOI: 10.34133/2020/2640834.].

The Possibility of Changing the Wettability of Material Surface by Adjusting Gravity.

The contact angle, as a vital measured parameter of wettability of material surface, has long been in dispute whether it is affected by gravity. Herein, we measured the advancing and receding contact angles on extremely low contact angle hysteresis surfaces under different gravities (1-8G) and found that both of them decrease with the increase of the gravity. The underlying mechanism is revealed to be the contact angle hysteresis and the deformation of the liquid-vapor interface away from the solid surface caused by gradient distribution of the hydrostatic pressure. The real contact angle is not affected by gravity and cannot measured by an optical method. The measured apparent contact angles are angles of inclination of the liquid-vapor interface away from the solid surface. Furthermore, a new equation is proposed based on the balance of forces acting on the three-phase contact region, which quantitatively reveals the relation of the apparent contact angle with the interfacial tensions and gravity. This finding can provide new horizons for solving the debate on whether gravity affects the contact angle and may be useful for the accurate measurement of the contact angle and the development of a new contact angle measurement system.

A Novel Approach to Accumulate Superparamagnetic Particles in Aqueous Environment Using Time-Varying Magnetic Field.

OBJECTIVE: Magnetic drug targeting (MDT) has attracted a lot of attention in recent years as a treatment to reduce side effects and improve efficacy. To realize successful MDT, a magnet system that can create suitable magnetic field is necessary. However, the existing technology has some shortcomings such as low targeting efficiency and unsatisfactory targeting effect. The method of using time-varying magnetic field proposed in this paper provides a new solution to this problem. METHODS: In this work, a permanent magnet system providing rotational magnetic field (a time-varying magnetic field) was designed and constructed. Focusing experiments of Fe3O4 particles were carried out in this system, and the mechanism of the focusing was discussed via a simplified model. RESULTS: By using the rotational magnetic field, superparamagnetic Fe3O4 particles can be successfully driven to the designated site within a short time. Our work showed that the time-varying magnetic field can drive the superparamagnetic particles to a focusing site, which is not possible under the same magnetic field without rotation, and the aggregation speed and effect are better than those under static field. CONCLUSION AND SIGNIFICANCE: Our results indicate that time-varying magnetic field can be a good choice for designing magnet systems for MDT. Moreover, the idea of using time-varying magnetic field for focusing superparamagnetic particles may be applicable in non-contact processings or manipulations of paramagnetic, superparamagnetic, or even ferromagnetic materials or objects in preparation of novel materials, robotic control of objects, and so on.

Comparison of stress response following microwave ablation and surgical resection of benign thyroid nodules.

PURPOSE: To compare the effects and safety of using microwave ablation (MWA) and surgical resection for the treatment of benign thyroid nodules (BTNs) under ultrasonic guidance and investigate the effects of this treatment on stress response. METHODS: Patients with BTNs were divided into the MWA and operation groups (72 cases each). Interleukin (IL)-6, IL-8, serum tumor necrosis factor (TNF-α), and hydrostatic visual analog scale (VAS) prior to the operation, at 6 h, 24 h, and 72 h post-operation were compared between the two groups. Operation times, hospitalization times, hospitalization expenses, and postoperative complications in the two groups were also compared. All patients underwent routine ultrasound and thyroid function testing at 3 and 6 months post-operation for assessment of nodule changes and thyroid hormone levels. RESULTS: Compared to the MWA group, the operation group had longer average operation times, longer hospital stays, a higher rate of neck pain after surgery, and a higher rate of fever (P < 0.05). Body temperature, as well as VAS, IL-6, IL-8, and TNF-α levels in the operation group were higher than those in the MWA group at 6 h, 24 h, and 72 h post-operation (P < 0.05). The levels of free thyroxine and free triiodothyronine in the operation group were lower than those in the MWA group (P < 0.05). CONCLUSION: MWA is a safe and effective treatment for patients with BTNs. The effects of MWA are more tolerable than those of surgical resection and the physiological function of the thyroid is preserved, which has high clinical value.

Effects of large gradient high magnetic field (LG-HMF) on the long-term culture of aquatic organisms: Planarians example.

Large gradient high magnetic field (LG-HMF) is a powerful tool to study the effects of altered gravity on organisms. In our study, a platform for the long-term culture of aquatic organisms was designed based on a special superconducting magnet with an LG-HMF, which can provide three apparent gravity levels (µ g, 1 g, and 2 g), along with a control condition on the ground. Planarians, Dugesia japonica, were head-amputated and cultured for 5 days in a platform for head reconstruction. After planarian head regeneration, all samples were taken out from the superconducting magnet for a behavioral test under geomagnetic field and normal gravity conditions. To analyze differences among the four groups, four aspects of the planarians were considered, including head regeneration rate, phototaxis response, locomotor velocity, and righting behavior. Data showed that there was no significant difference in the planarian head regeneration rate under simulated altered gravity. According to statistical analysis of the behavioral test, all of the groups had normal functioning of the phototaxis response, while the planarians that underwent head reconstruction under the microgravity environment had significantly slower locomotor velocity and spent more time in righting behavior. Furthermore, histological staining and immunohistochemistry results helped us reveal that the locomotor system of planarians was affected by the simulated microgravity environment. We further demonstrated that the circular muscle of the planarians was weakened (hematoxylin and eosin staining), and the epithelial cilia of the planarians were reduced (anti-acetylated tubulin staining) under the simulated microgravity environment. Bioelectromagnetics. 2018;39:428-440. © 2018 Wiley Periodicals, Inc.

[Sericin regulates proliferation of human gastric cancer MKN45 cells through autophagic pathway].

OBJECTIVE: To investigate the effect of sericin on the proliferation of human gastric cancer MKN45 cells and explore the underlying molecular mechanism. METHODS: MKN45 cells were transfected by LC3 double fluorescent autophagic virus, and the positive cells screened by puromycin were divided into blank group, sericin group and sericin∓3-MA group. After incubation with sericin for 48 h, the cells were examined for proliferation, apoptosis and cell cycle using CCK-8 assay and flow cytometry. Cell autophagy was detected by transmission electron microscopy (TEM) and fluorescent inverted microscope, and the autophagy-related markers including LC3, p62 and Beclin proteins were detected with Western blotting. Nude mice bearing gastric cancer xenograft were treated with normal saline or sericin injections (n=5) and the changes in the tumor volume and weight were measured. RESULTS: Compared with the blank group, MKN45 cells with sericin treatment showed significantly inhibited proliferation both in vitro and in nude mice. Autophagosomes were observed in sericin-treated cells under TEM and fluorescent inverted microscope. Sericin treatment of the cells significantly increased the cell apoptosis (P<0.01), caused obvious cell cycle arrest in G2/M phase (P<0.01), up-regulated the expressions of both LC3-2 and Beclin, and down-regulated the expression of p62. The autophagy inhibitor 3-MA obviously antagonized the effects of sericin on cell apoptosis, cell cycle and autophagic protein expressions. CONCLUSION: Sericin can inhibit the proliferation of human gastric cancer MKN45 cells by regulating cell autophagy to serve as potential anti-tumor agent.