A high security coding and anti-counterfeiting method based on the nonlinear magnetization response of superparamagnetic nanomaterials.

Traditional coding methods based on graphics and digital or magnetic labels have gradually decreased their anti-counterfeiting because of market popularity. This paper presents a new magnetic anti-counterfeiting coding method. This method uses a high-performance coding material, which, along with small changes to the material itself and the particle size of the superparamagnetic nanomaterials, results in a large difference in the nonlinear magnetization response. This method, which adopts 12-site coding and establishes a screening model by measuring the voltage amplitude of 12-site variables, can code different kinds of products, establishing long-term stable coding and decoding means. Through the anti-counterfeiting experiment of wine, the experiment results show that the authenticity of the coded products can be verified using the self-developed magnetic encoding and decoding system. The new coding technology can verify the anti-counterfeiting of 9000 products, with a single detection accuracy of 97% and a detection time of less than one minute. Moreover, this coding method completely depends on the production batch of the superparamagnetic nanomaterials, which is difficult to imitate, and it provides a new coding anti-counterfeiting technology for related industries with a wide range of potential applications.

Lappanolides A-N, fourteen undescribed sesquiterpenoids from Saussurea costus (Syn. Saussurea lappa) and their anti HBV activity.

Lappanolides A-N (1-14), 14 undescribed sesquiterpenoids, along with 23 known ones (15-37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC50 values ranging from 5.2 to 45.7 µM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC50 values of 5.28 and 5.30 µM, and CC50 values of 9.85 and 6.37 µM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis.

Measurement method of virtual image distance for a head-mounted display based on a variable-focus liquid lens.

The distance from the virtual image to the human eye is an important factor in measuring the comfort of a head-mounted display (HMD). However, accurately measuring their distance is challenging due to the dynamic changes in virtual presence and distance. In this paper, we proposed a virtual image distance measurement prototype based on a variable-focus liquid lens and derived a virtual image distance calculation model. We built a variable-focus liquid lens experimental platform to verify the method's correctness. In addition, we proposed an improved optimization algorithm that can efficiently and accurately search for the optimal focal length corresponding to the maximum sharpness moment of the virtual image within the focal length value space. Verified in an experimental scene of 0.5 m to 3.5 m, we observed that the error between the object image distance and the virtual image distance at the same focal length is about 5 cm. The proposed virtual image distance measurement method can accurately measure the distance value of the virtual image in the HMD. This method can be widely used in virtual and augmented reality, especially in the task of constructing realistic scenes.

Chloramphenicol alleviates 5-fluorouracil-induced cellular senescence through activation of autophagy.

5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-ß-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer.

Magnetic leakage behavior assessment in pipeline stress-concentrated areas using improved force-magnetic coupling model.

Magnetic flux leakage (MFL) technology is remarkable for its capability to detect pipeline geometric deformation and general corrosion defects. However, it cannot characterize the MFL behavior in stress-concentrated areas, thereby greatly challenging the subsequent pipeline maintenance. This study suggests that the MFL characteristics of pipeline in stress-concentrated areas are caused by the combined effect of the face magnetic charge on the deformed end-face and the body magnetic charge of the dislocation stack. In addition, an improved force-magnetic coupling model of the pipeline in stress-concentrated areas is established based on the magnetic dipole model and Jiles-Atherton (J-A) theory. In the verification experiment, the Q235 steel plate is magnetized along the extension direction (axis of the pipeline) through the solenoid coil to obtain the distribution law of the MFL signal in the stress-concentrated area under different excitation intensities. The results show that with the increase in excitation intensity, the deformation of the MFL field signal caused by the end-face of the stress-concentrated area gradually increases to a stable state. Moreover, the internal stress of the MFL field signal generated by the pipe dislocation rapidly increases to a peak value and then decays exponentially to a certain base value. The overall change trend is in good agreement with the calculation results of the established force-magnetic coupling model. Meanwhile, the differentiation research between deformation and internal stress MFL field signals under different magnetic field intensities can provide a reliable theoretical basis for the subsequent accurate identification and quantification of pipeline stress-concentrated areas.

4,4-Difluoroproline as a Unique 19F NMR Probe of Proline Conformation.

Despite the importance of proline conformational equilibria (trans versus cis amide and exo versus endo ring pucker) on protein structure and function, there is a lack of convenient ways to probe proline conformation. 4,4-Difluoroproline (Dfp) was identified to be a sensitive 19F NMR-based probe of proline conformational biases and cis-trans isomerism. Within model compounds and disordered peptides, the diastereotopic fluorines of Dfp exhibit similar chemical shifts (ΔδFF = 0-3 ppm) when a trans X-Dfp amide bond is present. In contrast, the diastereotopic fluorines exhibit a large (ΔδFF = 5-12 ppm) difference in chemical shift in a cis X-Dfp prolyl amide bond. DFT calculations, X-ray crystallography, and solid-state NMR spectroscopy indicated that ΔδFF directly reports on the relative preference of one proline ring pucker over the other: a fluorine which is pseudo-axial (i.e., the pro-4R-F in an exo ring pucker, or the pro-4S-F in an endo ring pucker) is downfield, while a fluorine which is pseudo-equatorial (i.e., pro-4S-F when exo, or pro-4R-F when endo) is upfield. Thus, when a proline is disordered (a mixture of exo and endo ring puckers, as at trans-Pro in peptides in water), it exhibits a small Δδ. In contrast, when the Pro is ordered (i.e., when one ring pucker is strongly preferred, as in cis-Pro amide bonds, where the endo ring pucker is strongly favored), a large Δδ is observed. Dfp can be used to identify inherent induced order in peptides and to quantify proline cis-trans isomerism. Using Dfp, we discovered that the stable polyproline II helix (PPII) formed in the denatured state (8 M urea) exhibits essentially equal populations of the exo and endo proline ring puckers. In addition, the data with Dfp suggested the specific stabilization of PPII by water over other polar solvents. These data strongly support the importance of carbonyl solvation and n → π* interactions for the stabilization of PPII. Dfp was also employed to quantify proline cis-trans isomerism as a function of phosphorylation and the R406W mutation in peptides derived from the intrinsically disordered protein tau. Dfp is minimally sterically disruptive and can be incorporated in expressed proteins, suggesting its broad application in understanding proline cis-trans isomerization, protein folding, and local order in intrinsically disordered proteins.

Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability.

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Metaplastic regeneration in the mouse stomach requires a reactive oxygen species pathway.

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.

The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.

INTRODUCTION: With age and ATP decrease in the body, the transcription factors hypophosphorylation weakens the transcription of Slc40a1 and hinders the expression of the iron discharger ferroportin. This may lead to iron accumulation in the brain and the catalysis of free radicals that damage cerebral neurons and eventually lead to Alzheimer's disease (AD). OBJECTIVES: To prevent AD caused by brain iron excretion disorders and reveal the mechanism of J bs-5YP peptide restoring ferroportin. METHODS: We prepared J bs-YP peptide and administered it to the senile mice with dementia. Then, the intelligence of the mice was tested using a Morris Water Maze. The ATP content in the body was detected using the ATP hydrophysis and Phosphate precipitation method. The activation of Slc40a1 transcription was assayed with ATAC seq and the ferroportin, as well as the phosphorylation levels of Ets1 in brain were detected by Western Blot. RESULTS: The phosphorylation level of Ets1in brain was enhanced, and subsequently, the transcription of Slc40a1 was activated and ferroportin was increased in the brain, the levels of iron and free radicals were reduced, with the neurons protection, and the dementia was ultimately alleviated in the senile mice. CONCLUSION: J bs-5YP can recover the expression of ferroportin to excrete excessive iron in the brain of senile mice with dementia by enhancing the transcription of Slc40a1 via phosphorylating Ets1, revealing the potential of J bs-5YP as a drug to alleviate senile dementia.

Development of a human-size magnetic particle imaging device for sentinel lymph node biopsy of breast cancer.

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 kHz@1.5 mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 µg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 µg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.

Metabolomics analysis to interpret changes in physiological and metabolic responses to chronic heat stress in Pekin ducks.

Heat stress (HS) is a major environmental threat that affects duck production in subtropical and tropical regions, especially in summer. This study aimed to evaluate the physiological and metabolic responses of Pekin ducks to chronic HS conditions via liquid chromatography-mass spectrometry (LC-MS) using a paired-fed (PF) experimental design. On the basis of equivalent feed intake (HS vs. PF), HS significantly reduced growth performance and the percentage of leg and breast muscles, however, markedly increased the percentage of abdominal fat and breast skin fat. Serum metabolomics results revealed that heat-stressed ducks showed enhanced glycolysis and pentose phosphate pathways, as demonstrated by higher glucose 6-phosphate and 6-phogluconic acid levels in the PF vs. HS comparison. HS decreased hepatic mRNA levels of mitochondrial fatty acid ß-oxidation-related genes (MCAD and SCAD) compared to the PF group, resulting in acetylcarnitine accumulation in serum. Moreover, HS elevated the concentrations of serum amino acids and mRNA levels of ubiquitination-related genes (MuRF1 and MAFbx) in the skeletal muscle and amino acid transporter-related genes (SLC1A1 and SLC7A1) and gluconeogenesis-related genes (PCK1 and PCase) in the liver compared to the PF group. When compared to the normal control group (NC), HS further decreased growth performance, but it elevated the abdominal fat rate. However, increased mRNA levels of ubiquitination-related genes and serum amino acid accumulation were not observed in the HS group compared to the NC group, implying that reduced feed intake masked the effect of HS on skeletal muscle breakdown and is a form of protection for the organism. These results suggest that chronic HS induces protein degradation in the skeletal muscle to provide amino acids for hepatic gluconeogenesis to provide sufficient energy, as Pekin ducks under HS conditions failed to efficiently oxidise fatty acids and ketones in the mitochondria, leading to poor growth performance and slaughter characteristics.

Uveal Melanoma Metastasis to the Thyroid.

Background: Around 1.2 to 3.1% of thyroid malignancies are due to metastasis. Among them, cutaneous malignant melanomas constitute 4% of malignancy metastasized to the thyroid. Uveal melanoma is uncommon, and its metastasis to the thyroid has only rarely been reported. Hereby, we describe an unusual case of uveal melanoma metastasized to the thyroid and discuss the concept of correct diagnosis. Case Report. During a routine ophthalmological examination, an 86-year-old Caucasian female was found to have retinal detachment secondary to choroidal melanoma. She was treated with gamma knife which resulted in reduction of tumor size. Three months later, she was noted to have a goiter on physical examination. Follow-up thyroid ultrasonography demonstrated numerous vascularized nodules in both lobes. The fine needle aspiration (FNA) of the left dominant nodule was indeterminate the first time and nondiagnostic the second time. FNA of the right dominant nodule was nondiagnostic twice but showed malignant cells the third time. Subsequent immunohistochemistry staining of the FNA sample from the right thyroid nodule confirmed a profile consistent with malignant melanoma. Conclusion: It should be kept in mind that a thyroid nodule detected in a patient with a diagnosis of uveal melanoma can be metastasis and that uveal melanoma diagnosis should be taken into account for the examination of the thyroid tumors of these patients. It is important to employ immunohistochemical staining FNA examination of the patient with such tumors for markers associated with a patient's known malignancy to facilitate diagnosis.

Peficitinib ameliorates doxorubicin-induced cardiotoxicity by suppressing cellular senescence and enhances its antitumor activity.

Irreversible cardiotoxicity limits the clinical applications of doxorubicin (DOX). Cardiotoxicity can be detected early using clinical assessment; however, effective preventive measures are still lacking. Peficitinib (ASP015K), a JAK (Janus kinase) inhibitor, is a potent anti-inflammatory agent in autoimmune diseases. Nevertheless, little research has been conducted on anti-ageing and anti-tumour therapies. In this study, we investigated whether ASP015K could attenuate DOX-induced cardiotoxicity through its anti-ageing effects and whether it would affect the tumour treatment effect of DOX by establishing senescence, acute heart injury, and xenograft models. We observed that ASP015K could antagonise the senescence induced by various factors, including hydrogen peroxide and DOX. In addition, ASP015K treatment significantly alleviated cardiac function damage, histopathological deterioration, myocardial fibrosis, and oxidative damage in acute injury mouse models. ASP015K enhanced the sensitivity of tumour cells to DOX therapy and significantly slowed down the tumour growth rate and tumour volume in the xenograft mouse model. Therefore, ASP015K is expected to be developed as a potential cardioprotective agent to prevent or reduce the cardiotoxic side effects of anthracyclines in chemotherapy.

Artesunate ameliorates irinotecan-induced intestinal injury by suppressing cellular senescence and significantly enhances anti-tumor activity.

Irinotecan (CPT-11) is a topoisomerase I inhibitor that was approved for cancer treatment in 1994. To date, this natural product derivative remains the world's leading antitumor drug. However, the clinical application of irinotecan is limited due to its side effects, the most troubling of which is intestinal toxicity. In addition, irinotecan has certain toxicity to cells and even causes cellular senescence. Committed to developing alternatives to prevent these adverse reactions, we evaluated the activity of artesunate, which has never been tested in this regard despite its biological potential. Irinotecan accelerated the process of aging in vivo and in vitro, and we found that this was mainly caused by activating mTOR signaling targets. Artesunate inhibited the activity of mTOR, thereby alleviating the aging process. Our study found that artesunate treatment improved irinotecan-induced intestinal inflammation by reducing the levels of TNF-α, IL1, and IL6; reducing inflammatory infiltration of the colonic ileum in mice; and preventing irinotecan-induced intestinal damage by reducing weight loss and improving intestinal length. In addition, in mouse xenograft tumor models, artesunate and irinotecan significantly inhibited tumor growth in mice.

PKM2 allosteric converter: A self-assembly peptide for suppressing renal cell carcinoma and sensitizing chemotherapy.

Stronger intrinsic Warburg effect and resistance to chemotherapy are the responses to high mortality of renal cell carcinoma (RCC). Pyruvate kinase M2 (PKM2) plays an important role in this process. Promoting PKM2 conversion from dimer to tetramer is a critical strategy to inhibit Warburg effect and reverse chemotherapy resistance. Herein, a PKM2 allosteric converter (PAC) is constructed based on the "in vivo self-assembly" strategy, which is able to continuously stimulate PKM2 tetramerization. The PAC contains three motifs, a serine site that is protected by enzyme cleavable ß-N-acetylglucosamine, a self-assembly peptide and a AIE motif. Once PAC nanoparticles reach tumor site via the EPR effect, the protective and hydrophilic ß-N-acetylglucosamine will be removed by over-expressed O-GlcNAcase (OGA), causing self-assembled peptides to transform into nanofibers with large serine (PKM2 tetramer activator) exposure and long-term retention, which promotes PKM2 tetramerization continuously. Our results show that PAC-induced PKM2 tetramerization inhibits aberrant metabolism mediated by Warburg effect in cytoplasm. In this way, tumor proliferation and metastasis behavior could be effectively inhibited. Meanwhile, PAC induced PKM2 tetramerization impedes the nuclear translocation of PKM2 dimer, which restores the sensitivity of cancer cells to first-line anticancer drugs. Collectively, the innovative PAC effectively promotes PKM2 conversion from dimer to tetramer, and it might provide a novel approach for suppressing RCC and enhancing chemotherapy sensitivity.

Crassaminicella indica sp. nov., a novel thermophilic anaerobic bacterium isolated from a deep-sea hydrothermal vent.

A novel moderately thermophilic heterotrophic bacterium, designated strain 143-21T, was isolated from a deep-sea hydrothermal chimney sample collected from the Central Indian Ridge at a depth of 2 440 m. Phylogenetic analysis indicated that strain 143-21T belongs to the genus Crassaminicella. It was most closely related to Crassaminicella thermophila SY095T (96.79 % 16S rRNA gene sequence similarity) and Crassaminicella profunda Ra1766HT (96.52 %). Genomic analysis showed that strain 143-21T shares 79.79-84.45 % average nucleotide identity and 23.50-29.20 % digital DNA-DNA hybridization with the species of the genus Crassaminicella, respectively. Cells were rod-shaped, non-motile, Gram-positive-staining. Terminal endospores were observed in stationary-phase cells when strain 143-21T was grown on Thermococcales rich medium. Strain 143-21T was able to grow at 30-60 °C (optimum, 50 °C), pH 6.5-8.5 (optimum, pH 7.0) and in 1.0-7.0 % NaCl (w/v; optimum 2.0 %, w/v). Strain 143-21T utilized fructose, glucose, maltose, mannose, ribose, N-acetyl-d-(+)-glucosamine and casamino acids, as well as amino acids including glutamate, lysine, histidine and cysteine. The main fermentation products from glucose were acetate (2.07 mM), H2 and CO2. It did not reduce elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe (III). The predominant cellular fatty acids were C14 : 0 (48.8 %), C16 : 0 (12.9 %), and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 10.2 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, as well as two unidentified phospholipids and four unidentified aminolipids. No respiratory quinones were detected. Based on its phylogenetic analysis and physiological characteristics, strain 143-21T is considered to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella indica sp. nov. is proposed. The type strain is strain 143-21T (=DSM 114408T= MCCC 1K06400T).

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

Elevated retinal retinol-binding protein 4 levels in diabetic mice can induce retinal neurodegeneration through microglia.

Retinol-binding protein 4 (RBP4) is the sole specific transport protein for vitamin A (retinol), but it is also an adipokine with retinol-independent, proinflammatory activity associated with diabetes and diabetic retinopathy (DR). Most previous studies focused on the relationship between elevated serum RBP4 levels and DR. Since serum RBP4 cannot cross the blood-retinal barrier, the level of retinal RBP4 is independent of serum RBP4, and the change of retinal RBP4 and its potential pathogenic mechanism in DR has not been studied. We showed that the retinal RBP4 levels were raised in Streptozotocin-induced diabetic mice though the serum RBP4 levels were decreased. Intravitreal injection of RBP4 protein in mice results in activation of microglia, loss of retinal ganglion cells (RGCs) and bipolar cells. Minocycline (MC) can reverse the activation of microglia induced by RBP4, protecting RGCs and bipolar cells. These findings suggest that retinal RBP4 levels were raised in diabetic mice, and RBP4 can directly induce retinal neurodegeneration in mice through microglia. RESEARCH HIGHLIGHTS: We revealed that the retinal RBP4 levels were raised in diabetes and elevated retinal RBP4 can induce retinal neurodegeneration through microglia. Inhibition of neuroinflammation or reduction of retinal RBP4 level may be a potential therapeutic strategy to prevent diabetic retinal neurodegeration.

Research progress of exosomes in drug resistance of breast cancer.

Since breast cancer is a heterogeneous disease, there are currently a variety of treatment methods available, including chemotherapy, endocrine therapy, molecular targeted therapy, immunotherapy, radiation therapy, etc. Breast cancer recurrence and metastasis, despite many treatment modalities, constitute a considerable threat to patients' survival time and pose a clinical challenge that is difficult to tackle precisely. Exosomes have a very special and crucial role in the treatment of drug resistance in breast cancer as a carrier of intercellular communication in the tumor microenvironment. Exosomes and breast cancer treatment resistance have been linked in a growing number of clinical investigations in recent years. This paper covers the status of research on exosomes in the treatment of breast cancer drug resistance and offers theoretical guidance for investigating new strategies to treat breast cancer drug resistance.

Biomechanical analysis of stress around the tilted implants with different cantilever lengths in all-on-4 concept.

BACKGROUND: Many clinical studies have reported the high success rate of the All-on-4 concept. In the present study, we aimed to compare the stress distribution with different tilted distal implants and cantilever lengths in an All-on-4 system using the two-dimensional photoelastic method and to establish the All-on-4 implant photoelastic model by computer-aided design (CAD) and rapid prototyping (RP).  METHODS: The data of the human edentulous mandible were acquired by computed tomography (CT). Three human edentulous mandible All-on-4 implant models with different distally inclined implant holes were fabricated using Mimic, Geomagic Studio software, and a light solidifying fast shaping machine. Then the final photoelastic models were established through the traditional method. Each of the three models had four NobelSpeedy Replace implants between the interforaminal regions. The two posterior implants were placed 0, 15, and 45 degrees distally before the mental foramen. The four implants were splinted by wrought cobalt-chromium alloy frameworks. Each of the three photoelastic models was submitted to a 150 N vertical load at five points on the framework: the central fossa of the mandibular first molar, and 0 mm, 5 mm, 10 mm, and 15 mm of the cantilever length. The stress produced in the models was photographed with a digital camera, and the highest value of the stressed fringe pattern was recorded. RESULTS: The All-on-4 implant photoelastic model established by CAD and RP was highly controllable and easy to modify. The position and inclination of implants were accurate, and the frameworks could be passively emplaced. The stress values were higher around a single tilted implant compared with the distal implant in All-on-4 with the same inclination. The 0-degree distal implant and 45-degree distal implant demonstrated the highest and lowest stress when loading at the central fossa of the mandibular first molar, respectively. With the same inclination of distal implant, the peri-implant bone stress increased as the length of cantilever increased. CONCLUSION: The method of establishing the All-on-4 implant photoelastic model by CAD and RP was highly controllable, convenient, fast, and accurate. The tilted implants splinted in the fully fixed prosthesis with reduced cantilever lengths did not increase the stress level compared with the vertical distal implants.And this illustrated that the influence of cantilever on stress distribution was greater than the influence of implant inlination.