Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization.

Immune checkpoint therapy has limited efficacy for patients with bone-metastatic castration-resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC-induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32-gene M2-like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206-positive (CD206+) macrophages were enriched in bmCRPC bone biopsy specimens compared with primary tumors or lymph node metastases. In preclinical osteogenic prostate cancer (Pca) xenograft models, CD206+ macrophages were recruited to areas with tumor-induced bone. RNA sequencing (RNAseq) analysis showed higher expression of an M2-like gene signature, with activated canonical and noncanonical Wnt pathways, in tumor-associated macrophages isolated from osteogenic tumors (bone-TAMs) than in TAMs isolated from nonosteogenic tumors (ctrl-TAMs). Mechanistic studies showed that endothelial cells (ECs) that had undergone EC-to-osteoblast (EC-to-OSB) transition, the precursors of tumor-induced OSBs, produced paracrine factors, including Wnts, CXCL14, and lysyl oxidase, which induced M2 polarization and recruited M2-like TAMs to the bone-tumor microenvironment (bone-TME). Bone-TAMs suppressed CD8+ T cells' proliferation and cytolytic activity, and these effects were partially reversed by treating bone-TAMs with Wnt inhibitors. Genetic or pharmacological inhibition of Pca-induced EC-to-OSB transition reduced the levels of M2-like macrophages in osteogenic tumors. Our study demonstrates that Pca-induced EC-to-OSB transition drives immunosuppression in the bone-TME, suggesting that therapies that reduce Pca-induced bone formation may improve immunotherapeutic outcomes for bmCRPC.

Electronic Structure and Chemical Bonding of the First-, Second-, and Third-Row-Transition-Metal Monoborides: The Formation of Quadruple Bonds in RhB, RuB, and TcB.

Boron presents an important role in chemistry, biology, and materials science. Diatomic transition-metal borides (MBs) are the building blocks of many complexes and materials, and they present unique electronic structures with interesting and peculiar properties and a variety of bonding schemes which are analyzed here. In the first part of this paper, we present a review on the available experimental and theoretical studies on the first-row-transition-metal borides, i.e., ScB, TiB, VB, CrB, MnB, FeB, CoB, NiB, CuB, and ZnB; the second-row-transition-metal borides, i.e., YB, ZrB, NbB, MoB, TcB, RuB, RhB, PdB, AgB, and CdB; and the third-row-transition-metal borides, i.e., LaB, HfB, TaB, WB, ReB, OsB, IrB, PtB, AuB, and HgB. Consequently, in the second part, the second- and third-row MBs are studied via DFT calculations using the B3LYP, TPSSh, and MN15 functionals and, in some cases, via multi-reference methods, MRCISD+Q, in conjunction with the aug-cc-pVQZ-PPM/aug-cc-pVQZB basis sets. Specifically, bond distances, dissociation energies, frequencies, dipole moments, and natural NPA charges are reported. Comparisons between MB molecules along the three rows are presented, and their differences and similarities are analyzed. The bonding of the diatomic borides is also described; it is found that, apart from RhB(X1Σ+), which was just recently found to form quadruple bonds, RuB(X2Δ) and TcB(X3Σ-) also form quadruple σ2σ2π2π2 bonds in their X states. Moreover, to fill the gap existing in the current literature, here, we calculate the TcB molecule.

Osteoblastic Factors in Prostate Cancer Bone Metastasis.

PURPOSE OF REVIEW: Prostate cancer bone metastasis is the lethal progression of the disease. The disease frequently presents with osteoblastic lesions in bone. The tumor-induced bone can cause complications that significantly hamper the quality of life of patients. A better understanding of how prostate cancer induces aberrant bone formation and how the aberrant bone affects the progression and treatment of the disease may improve the therapies for this disease. RECENT FINDINGS: Prostate cancer-induced bone was shown to enhance tumor growth and confer therapeutic resistance in bone metastasis. Clinically, Radium-223, an alpha emitter that selectively targets bone, was shown to improve overall survival in patients, supporting a role of tumor-induced bone in prostate cancer progression in bone. Recently, it was discovered that PCa-induced aberrant bone formation is due, in part, from tumor-associated endothelial cells that were converted into osteoblasts through endothelial-to-osteoblast (EC-to-OSB) conversion by tumor-secreted BMP4. The unique bone-forming phenotype of prostate cancer bone metastasis plays a role in prostate cancer progression in bone and therapy resistance. Therapies that incorporate targeting the tumor-induced osteoblasts or EC-to-OSB conversion mechanism may reduce tumor-induced bone formation and improve therapy outcomes.

In Situ Formation of Compound Eye-like SAN-OSB Composite Microspheres by Melt-Blending Method: Enhancing Multiple-Scattering Effect.

The preparation of novel structures of light-diffusing particles is currently a research focus in the field of light-diffusing materials. This study, conducted by the common melt-blending process, controlled thermodynamic and kinetic factors to distribute smaller-sized organic silica bead (OSB) particles at the interface between a polycarbonate (PC) matrix and spherical island-phase styrene-acrylonitrile copolymer (SAN) for the in situ formation of compound eye-like microspheres with SAN as "large eyes" and OSBs as "small eyes". Through the multiple-scattering effects of these compound eye-like microspheres, these light-diffusing materials significantly improved the haze, scattering range, and light-shielding capabilities while maintaining high transmittance. Specifically, the PC/SAN-OSB light-scattering materials achieved a haze of 100% with an OSB content of only 0.17%, maintaining a transmittance of 88%. Compared with the PC/OSB system with the same level of haze, the addition of OSB was reduced by 88%. Therefore, this study achieved exceptionally effective light-diffusing materials through a simple, environmentally friendly, and low-cost preparation method, suitable for the scalable production of light-diffusing materials in new display and lighting fields.

Ion-Exchanging Lead-Free Perovskite with Tunable Emission Wavelengths for Chemical and Fluorescent Double-Modal Anticounterfeiting Application.

Novel and covert fluorescence is quite desirable for fluorescent anticounterfeiting application. Here, Cs2InCl5·H2O/Sb and Cs2NaInCl6/Sb with high photoluminescence quantum yields (PLQYs) of 99.61 and 99.9%, respectively, were achieved. Considering the excellent optical performances together with the high similarity of the two crystal structures, we tried to realize the crystal structure transition from Cs2InCl5·H2O/Sb to Cs2NaInCl6/Sb by an ion-exchange method. It was well done by just adding the NaCl precursor with different concentrations in the Cs2InCl5·H2O/Sb product. Interestingly, a gradual color change from yellow to orange, warm white, white, cool white, and blue was achieved in the process of crystal structure transition. The energy-transfer dynamic models of Cs2InCl5·H2O/Sb, the white product, and Cs2NaInCl6/Sb were identified. The chemical reaction and UV fluorescence properties made it possible for application in chemical and fluorescent double-modal anticounterfeiting and highly decreased the possibility of being cracked and copied. Especially, when salt for daily cooking was used to replace NaCl, a similar phenomenon happened as that of the 99.9% NaCl precursor, which made it easy to be applicated. The combination of chemical and optical verifications provides two levels of security and unbreakable encryption. The results demonstrate that the transition from Cs2InCl5·H2O/Sb to Cs2NaInCl6/Sb is highly promising in fluorescent anticounterfeiting application.

Composite Beams Made of Waste Wood-Particle Boards, Fastened to Solid Timber Frame by Dowel-Type Fasteners.

To increase the sustainability of prefabricated timber buildings and constructions, composite timber beams with "box" cross-sections were developed in collaboration with an industry partner. They were constructed from a solid timber frame and from webs made of residual waste wood-particle boards from prefabricated timber buildings production. The developed beams' design concepts presented in this paper were governed by architectural features of prefabricated timber buildings, geometrical limitations, available production technology, and structural demand related to various possible applications. The paper presents the results of experimental bending tests of six variations of the developed composite timber beams constructed by mechanical fasteners only. The developed design concept of composite timber beams without adhesives is beneficial compared to glued beams in terms of design for deconstruction and lower VOC emissions. The tests were conducted to study the influence of the following parameters on the beams' mechanical behavior: (i) web material (oriented strand boards (OSBs) vs. cement-particle boards); (ii) the influence of beam timber frame design (flanges and web stiffeners vs. flanges, web stiffeners, and compressive diagonals), and (iii) the influence of stiffener-flange joint design. Besides the beams' load-bearing capacities, their linear and non-linear stiffness characteristics were the main research interest. While adding compressive timber diagonals did not prove to significantly increase the stiffness of the beams in the case of cement-particle board webs, it increased their load-bearing capacity by enabling the failure of flanges instead of prior webs and stiffener-flange joints failure. For beams with OSB webs, failure of the bottom flange was achieved already with the "basic" timber frame design, but timber diagonals proved beneficial to increase the stiffness characteristics. Finally, mechanical characteristics of the developed beams needed in structural design for their application are provided together with further development guidelines.

Fast Pyrolysis Bio-Oil-Based Epoxy as an Adhesive in Oriented Strand Board Production.

The objectives of this study were to utilize bio-oil-based epoxy resin in oriented strand board (OSB) production and investigate the effect of bio-oil substitution in epoxy resin as an adhesive for OSB production. Bio-oil was produced by the fast pyrolysis (FP) process using southern yellow pine (Pinus spp.). Bio-oil-based epoxy resin was synthesized by the modification of epoxy resin with FP bio-oil at various substitution levels. Acetone extraction using a Soxhlet process indicated a superior cured reaction of bio-oil and epoxy resin at 20% bio-oil substitution. FTIR spectra corroborated the Soxhlet extraction with the removal of the epoxide peak signature within the cross-linked polymer. Images from the scanning electron microscopy suggested bulk phase homogeneity. OSB panels were tested according to ASTM D1037-12. The modulus of rupture (MOR), modulus of elasticity (MOE), internal bond strength, and water resistance (thickness swell and water absorption) properties of the OSB panels were feasible at bio-oil substitution up to 30% in the epoxy resin system.

The Effect of Openings' Size and Location on Selected Dynamical Properties of Typical Wood Frame Walls.

The wooden frame constructions are now popular in many developed countries of the world. Many of these locations where such buildings are constructed are exposed to seismic and other shocks which are generated by human activities. This paper discusses the effect of the size and location of openings in the wooden frame walls under dynamic loadings. Natural frequencies of such frames with and without openings have been determined. Three 14 m high walls with different widths, including 3, 6, and 12 m, have been considered. Dynamic analysis has been made using finite element method structural analysis software Dlubal RFEM 5.17. The results show that the effect of the size and location of the openings on the natural frequency is significant. Numerically speaking, the relative change of the natural frequencies of a wall without and with an opening in a specific place could be up to 30%. In addition, the change of the natural frequency for the location of the openings is more sensitive than that to the sizes. Furthermore, the appropriate sizes and locations of openings of the wooden frame walls have been suggested. The appropriate size and place were found to be small openings in the top of the walls.

Experimental Study of Oriented Strand Board Ignition by Radiant Heat Fluxes.

Wood and composite panel materials represent a substantial part of the fuel in many building fires. The ability of materials to ignite when heated at elevated temperatures depends on many factors, such as the thermal properties of materials, the ignition temperature, critical heat flux and the environment. Oriented strand board (OSB) without any surface treatment in thicknesses of 12, 15 and 18 mm were used as experimental samples. The samples were gradually exposed to a heat flux of 43 to 50 kW.m-2, with an increase of 1 kW.m-2. At heat fluxes of 49 kW.m-2 and 50 kW.m-2, the ignition times are similar in all OSB thicknesses, in contrast to the ignition times at lower heat fluxes. The influence of the selected factors (thickness and distance from the heat source) was analysed based on the experimentally obtained data of ignition time and weight loss. The experimentally determined value of the heat flux density was 43 kW.m-2, which represented the critical heat flux. The results show a statistically significant effect of OSB thickness on ignition time.

Rheological Relaxation of OSB Beams Reinforced with CFRP Composites.

An experimental and analytical approach to the relaxation problem of wood-based materials-OSB (Oriented Strand Boards-pressed wood-based composite panels) beams, including beams with CFRP (Carbon fiber reinforced polymer) tape composite reinforcement, is presented. It is a relevant engineering and scientific problem due to the fact that wood and wood-based materials, as well as composite reinforcements, are widely used in building constructions. Their rheological properties are very important and complicated to estimate. A 10 day long relaxation test of thick OSB beams without reinforcement and with CFRP tape was performed. A four-point bending test with five different bending levels was performed, during which the reduction of the loading force was measured. A five-parameter rheological model was used to describe the rheology of the beams. The equations of this model were calculated with the use of Laplace transform, whereas the values of the parameters were calculated based on the experimental relaxation curves. A high correlation between experimental and theoretical results was obtained. A beam reinforced with CFRP tape was treated as a system with a viscoelastic element (OSB) and an elastic element (CFRP), joined together without the possibility of slipping. The equations of the mathematical model were calculated based on the assumptions of the linear theory of viscoelasticity and the convolution integral. A good correlation between experimental and theoretical results was obtained. A significant redistribution of stresses was observed during the relaxation of the reinforced beam. The reinforced beams show a higher stiffness of approximately 63% and carry proportionally higher loads than unreinforced beams at the same deflection values.

The Clinical Value of Prenatal 3D Ultrasonic Diagnosis on Fetus Hemivertebra Deformity- A Preliminary Study.

OBJECTIVE: The present study is planned to discuss the clinical value of prenatal 3D ultra-sonic diagnosis on fetus hemivertebra deformity through the retrospective analysis of clinical data of fetus hemivertebra deformity. METHODS: Selected 9 fetus hemivertebra deformity cases, which have been admitted to our hospital during the period from January, 2010 to January, 2016 as study samples, and analyzed their 2D and 3D ultrasonic examination data. RESULTS: 4 cases of the fetus hemivertebra deformity occurred at lumbar vertebra, 3 cases at thoracic vertebra, and 2 cases at thoracolumbar vertebra. There were scoliosis and opened spine bifida (OSB). In 7 cases, there was absence of ribs in fetus. The 2D ultrasonic image showed that: The echo at the center of fetus vertebral arch lesion was blurred or lost. The coronal section showed the deformity of the spine. There was obvious loss of the ossification center. From the cross section, we could see that the vertebral body of the fetus was shrinking and the edges were relatively blurred. The 3D ultrasonic image showed that: the echo at the ossification center of the fetus vertebra was relatively blurred, or even lost. The image also indicated scoliosis deformity of the spine. The vertebral body lesion could be accurately located. CONCLUSION: 9 cases of fetus hemivertebra deformity have been detected through examination. Labor inductions have been carried out after getting the permission from the family members. The X-ray examination of the fetus after labor induction showed that the diagnosis was correct. Prenatal ultra-sonic examination holds strong potential for the diagnosis of fetus hemivertebra deformity quite early and deserves further clinical evaluation with large sample size.

Surgical Management of Laterognathia in Orthofacial Surgery.

INTRODUCTION: Each year around the world, various surgical procedures are carried out with the goal of correcting laterognathia; both the intraoral vertical ramus osteotomy (IVRO) and bilateral sagittal split ramus osteotomy (OSB) have been the most used techniques in mandibular surgery. These techniques have advantages and disadvantages; for example the advantages of the OSB include: increased coefficient of friction between bony segments, for both the forward and the retroposition, as well as decrease in the time of intermaxillary fixation (IMF). Disadvantages include injury to the inferior alveolar nerve (IAN), hemorrhage, bad split, among others. The advantages of IVRO include decrease of possibility of injury to the IAN, ease of implementation of the technique, a lower incidence of hemorrhage and the short duration of the surgical procedure. Their disadvantages include: lower coefficient of friction between bony segments, requires a relatively long period of IMF. The combination between the techniques of mandibular osteotomy for the correction of minor 10 mm laterognathia is the ideal treatment, since it avoids potential recurrence. MATERIALS AND METHODS: We describe two cases of patients with laterognathia greater than 6 mm associated with maxilla deformity, which were treated with combined osteotomies. At Maxillofacial Surgery Service, Specialty Hospital, National Medical Center XXI Century, we describe the advantages and disadvantages, pre and postoperative nosocomial, by comparing them with the reports of the literature. CONCLUSION: The combination of techniques in the correction of laterognathias greater than 4 mm (smaller than 10 mm) is the ideal treatment, eliminating problems of articular compression, recurrence and damage to the alveolar nerve.

Identification of differentially-expressed genes potentially implicated in drought response in pitaya (Hylocereus undatus) by suppression subtractive hybridization and cDNA microarray analysis.

Drought is one of the most severe threats to the growth, development and yield of plant. In order to unravel the molecular basis underlying the high tolerance of pitaya (Hylocereus undatus) to drought stress, suppression subtractive hybridization (SSH) and cDNA microarray approaches were firstly combined to identify the potential important or novel genes involved in the plant responses to drought stress. The forward (drought over drought-free) and reverse (drought-free over drought) suppression subtractive cDNA libraries were constructed using in vitro shoots of cultivar 'Zihonglong' exposed to drought stress and drought-free (control). A total of 2112 clones, among which half were from either forward or reverse SSH library, were randomly picked up to construct a pitaya cDNA microarray. Microarray analysis was carried out to verify the expression fluctuations of this set of clones upon drought treatment compared with the controls. A total of 309 expressed sequence tags (ESTs), 153 from forward library and 156 from reverse library, were obtained, and 138 unique ESTs were identified after sequencing by clustering and blast analyses, which included genes that had been previously reported as responsive to water stress as well as some functionally unknown genes. Thirty six genes were mapped to 47 KEGG pathways, including carbohydrate metabolism, lipid metabolism, energy metabolism, nucleotide metabolism, and amino acid metabolism of pitaya. Expression analysis of the selected ESTs by reverse transcriptase polymerase chain reaction (RT-PCR) corroborated the results of differential screening. Moreover, time-course expression patterns of these selected ESTs further confirmed that they were closely responsive to drought treatment. Among the differentially expressed genes (DEGs), many are related to stress tolerances including drought tolerance. Thereby, the mechanism of drought tolerance of this pitaya genotype is a very complex physiological and biochemical process, in which multiple metabolism pathways and many genes were implicated. The data gained herein provide an insight into the mechanism underlying the drought stress tolerance of pitaya, as well as may facilitate the screening of candidate genes for drought tolerance.