Recent Advances in the Epidemiology of Pathogenic Agents.

The COVID-19 pandemic has underscored the pivotal role of epidemiology in studying pathogenic agents [...].

Biomimetic vascularized adipose-derived mesenchymal stem cells bone-periosteum graft enhances angiogenesis and osteogenesis in a male rabbit spine fusion model.

Aims: Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods: A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials - acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC - were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results: At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson's trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion: The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes.

Developing a novel quasi-3D movable water phantom for radiation therapy workable in the magnetic resonance environment.

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA. Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift. Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity. Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists.

Enhanced Superconductivity and Rashba Effect in a Buckled Plumbene-Au Kagome Superstructure.

Plumbene, with a structure similar to graphene, is expected to possess a strong spin-orbit coupling and thus enhances its superconducting critical temperature (Tc ). In this work, a buckled plumbene-Au Kagome superstructure grown by depositing Au on Pb(111) is investigated. The superconducting gap monitored by temperature-dependent scanning tunneling microscopy/spectroscopy shows that the buckled plumbene-Au Kagome superstructure not only has an enhanced Tc with respect to that of a monolayer Pb but also possesses a higher value than what owned by a bulk Pb substrate. By combining angle-resolved photoemission spectroscopy with density functional theory, the monolayer Au-intercalated low-buckled plumbene sandwiched between the top Au Kagome layer and the bottom Pb(111) substrate is confirmed and the electron-phonon coupling-enhanced superconductivity is revealed. This work demonstrates that a buckled plumbene-Au Kagome superstructure can enhance superconducting Tc and Rashba effect, effectively triggering the novel properties of a plumbene.

Formation of surface states on Pb(111) by Au adsorption.

Using low-energy electron diffraction and angle-resolved photoemission spectroscopy, we investigated the lattice and electronic structures of the Pb(111) surface upon the adsorption of Au atoms at the low temperature T = 40 K. Unlike earlier results showing the formation of PbAu-alloy layers at room temperature, we found that Au atoms form a ultra-thin superstructure, Au/Pb(111)-3 × 3, on top of the Pb(111) surface. Moreover, three surface-state bands, S1, S2, and S3, are induced within and immediately adjacent to the Pb bulk projected band gap centered at the surface zone boundary [Formula: see text] at the energies of - 0.02, - 1.05, and - 2.56 eV, respectively. First-principles calculation based on Au/Pb(111)-3 × 3 confirms the measured surface-state bands among which the most interesting are the S1 and S3 surface states. They are derived from surface resonances in Pb(111). Moreover, S1, which disperses across Fermi level, exhibits a large anisotropic Rashba splitting with α of 1.0 and 3.54 eVÅ in the two symmetry directions centered at [Formula: see text]. The corresponding Rashba splitting of S1 band in Cu/Pb(111)-3 × 3 and Ag/Pb(111)-3 × 3 were calculated for comparison.

Experimental Observation of Isolative Efficacy of a Solid Coupling Medium in Extracorporeal Shock Wave Lithotripsy-Implications to Nosocomial Infection Prevention.

Introduction: Extracorporeal shock wave lithotripsy (ESWL) is a well-established, popular treatment choice for renal stones. Traditionally, the semi-liquid gel is used as a coupling medium in ESWL. During ESWL, body fluid or blood might transmit between the patients when the probe or gel used in the procedure is contaminated and cause potential nosocomial infections. To solve this problem, we developed a solid coupling medium (isolation coupling pad, referred to as "icPad") between the patient's skin and the probe as a shock wave transmission medium to prevent contamination. This study aimed to investigate the isolative efficacy of the icPad in blocking the permeation of microbes. Method: Rhodamine 6G (a fluorescent dye) was used as a tracer to simulate the microorganisms. The penetration of the fluorescent dye on the longitudinal section of the icPad was observed by a microscope after the dye was placed on the body side of the icPad for 40 min. After the shock wave, icPad was extracted with 75% ethanol, and fluorescence intensity was measured with a fluorescence spectrometer. Results: Our results revealed that the body side of icPad is free of fluorescent dye during lithotripsy. Qualitative analysis results confirmed that icPad has an isolative effect on simulating contaminants such as bacteria or viruses. Conclusion: In this in vitro phantom study, a proprietary icPad can be an isolative coupling medium and is speculated to avoid cross-contamination of bacterial or viral infection during ESWL.

A clinical observational study of effectiveness of a solid coupling medium in extracorporeal shock wave lithotripsy.

This study aimed to investigate clinical effectiveness of stone disintegration by using isolation coupling pad ("icPad") as coupling medium to reduce trapped air pockets during extracorporeal shock wave lithotripsy (ESWL). Patients underwent ESWL between Oct. 2017 and May 2018 were enrolled in this clinical observational study. An electromagnetic lithotripter (Dornier MedTech Europe GmbH Co., Germany) was used in this study. Patients were divided into icPad group P1, P2 and semi-gel group C by different coupling medium. The energy level and total number of shock wave (SW) for group P1 and C was set at level 2 and 3000 and group P2 at level 3 and 2500. The successful stone disintegration rate (SSDR) was determined to evaluate the treatment outcome. All patients were evaluated by KUB film and ultrasonography after 90 days. Complications during ESWL were recorded. A total of 300 patients satisfied the inclusion criteria. There were no significant differences in characteristics of patients and stone among three groups. The corresponding SSDRs for patients in group P1, P2 and C was 73.0%, 73.2% and 55.3%, respectively. The SSDR in group P1 was statistically higher than Group C. Comparing to semi-liquid gel, coupling medium using by icPad could achieve better treatment outcome of stone disintegration in ESWL.

Topological Proximity-Induced Dirac Fermion in Two-Dimensional Antimonene.

Antimonene is a promising two-dimensional (2D) material that is calculated to have a significant fundamental bandgap usable for advanced applications such as field-effect transistors, photoelectric devices, and the quantum-spin Hall (QSH) state. Herein, we demonstrate a phenomenon termed topological proximity effect, which occurs between a 2D material and a three-dimensional (3D) topological insulator (TI). We provide strong evidence derived from hydrogen etching on Sb2Te3 that large-area and well-ordered antimonene presents a 2D topological state. Delicate analysis with a scanning tunneling microscope of the evolutionary intermediates reveals that hydrogen etching on Sb2Te3 resulted in the formation of a large area of antimonene with a buckled structure. A topological state formed in the antimonene/Sb2Te3 heterostructure was confirmed with angle-resolved photoemission spectra and density-functional theory calculations; in particular, the Dirac point was located almost at the Fermi level. The results reveal that Dirac fermions are indeed realized at the interface of a 2D normal insulator (NI) and a 3D TI as a result of strong hybridization between antimonene and Sb2Te3. Our work demonstrates that the position of the Dirac point and the shape of the Dirac surface state can be tuned by varying the energy position of the NI valence band, which modifies the direction of the spin texture of Sb-BL/Sb2Te3 via varying the Fermi level. This topological phase in 2D-material engineering has generated a paradigm in that the topological proximity effect at the NI/TI interface has been realized, which demonstrates a way to create QSH systems in 2D-material TI heterostructures.

Newly designed solid coupling medium for reducing trapped air pockets during extracorporeal shock wave lithotripsy_ a phantom study.

INTRODUCTION: Air pockets between the lithotripter head and body surface are almost inevitably generated when applying a handful of gel onto the contact portion of the treatment head and that on the patient's skin during coupling procedure. These air pockets can compromise the transmission of acoustic energy of shock wave and may significantly affect efficacy of stone disintegration. Comparing to conventional gel, this study aims to investigate efficacy of stone disintegration by using a proprietary isolation-coupling pad ("icPad") as the coupling medium to reduce trapped air pockets during ESWL procedure. METHOD: In this phantom study, Dornier lithotripter (Delta-2 RC, Dornier MedTech Europe GmbH Co., Germany) was used with a proprietary gel pads (icPad, Diameter = 150 mm, Thickness = 4 mm and 8 mm). The lithotripter was equipped with inline camera to observe the trapped air pockets between the contact surface of the lithotripter head. A testing and measuring device were used to observe experimental stone disintegration using icPad and semi-liquid gel. The conventional semi-liquid gel was used as control for result comparison. RESULTS: The stone disintegration rate of icPad 4 mm and 8 mm after 200 shocks of energy at level 2 were significantly higher than that of the semi-liquid gel (disintegration rate 92.3%, 85.0% vs. 45.5%, respectively, p < 0.001). The number of shocks for complete stone disintegration by icPad of 4 mm and 8 mm at the same energy level 2 were significantly lower than that of the semi-liquid gel (the number of shocks 242.0 ± 13.8, 248.7 ± 6.3 vs. 351.0 ± 54.6, respectively, p = 0.011). Furthermore, quantitative comparison of observed air pockets under Optical Coupling Control (OCC) system showed that the area of air pockets in semi-liquid group was significantly larger than that of the group using icPad (8 mm) and that of the group using icPad (8 mm) after sliding (332.7 ± 91.2 vs. 50.3 ± 31.9, 120.3 ± 21.5, respectively, p < 0.05). CONCLUSION: The advantages of icPad includes: (1) reduced the numbers of shock wave and increased stone disintegration rate due to icPad's superior efficacy; (2) significantly reduce trapped air pockets in ESWL coupling. Due to the study limitation, more data are needed to confirm our observations before human trials.

Exploring Dual-Substrate Cultivation Strategy of 1,3-Propanediol Production Using Klebsiella pneumoniae.

1,3-Propanediol (1,3-PDO) has numerous industrial applications in the synthesis of the monomer of the widely used fiber polytrimethylene terephthalate. In this work, the production of 1,3-PDO by Klebsiella pneumoniae is increased by dual-substrate cultivation and fed-batch fermentation. Experimental results indicate that the production of 1,3-PDO can be elevated to 16.09 g/L using a dual substrate ratio (of glucose to crude glycerol) of 1/30 and to 20.73 g/L using an optimized dual-substrate ratio of 1/20. Ultimately, the optimal dual-substrate feeding for a 5 L scale fed-batch fermenter that maximizes 1,3-PDO production (29.69 g/L) is determined. This production yield is better than that reported in most related studies. Eventually, the molecular weight and chemical structure of 1,3-PDO were obtained by FAB-MS, 1H-NMR, and 13C-NMR. Also, in demonstrating the effectiveness of the fermentation strategy in increasing the production and production yield of 1,3-PDO, experimental results indicate that the fermentation of 1,3-PDO is highly promising for commercialization.

Ectoine production with indigenous Marinococcus sp. MAR2 isolated from the marine environment.

Ectoine has fostered the development of products for skin care and cosmetics. In this study, we employed the marine bacterial strain Marinococcus sp. MAR2 to increase ectoine production by optimizing medium constituents using Response Surface Methodology (RSM) and a fed-batch strategy. The results from the steepest ascent and central composite design indicated that 54 g/L of yeast extract, 14.0 g/L of ammonium acetate, 74.4 g/L of sodium glutamate, and 6.2 g/L of sodium citrate constituted the optimal medium with maximum ectoine production (3.5 g/L). In addition, we performed fed-batch culture in the bioreactor, combining pH and dissolved oxygen to produce ectoine by Marinococcus sp. MAR2. The ectoine production, content, and productivity of 5.6 g/L, 10%, and 3.9 g/L/day were further reached by a fed-batch culture. Thus, the ectoine production by Marinococcus sp. MAR2 using RSM and fed-batch strategy shows its potential for industrial production.

WMJ-S-001, a Novel Aliphatic Hydroxamate-Based Compound, Suppresses Lymphangiogenesis Through p38mapk-p53-survivin Signaling Cascade.

Background and purpose: Angiogenesis and lymphangiogenesis are major routes for metastatic spread of tumor cells. It thus represent the rational targets for therapeutic intervention of cancer. Recently, we showed that a novel aliphatic hydroxamate-based compound, WMJ-S-001, exhibits anti-angiogenic, anti-inflammatory and anti-tumor properties. However, whether WMJ-S-001 is capable of suppressing lymphangiogenesis remains unclear. We are thus interested in exploring WMJ-S-001's anti-lymphangiogenic mechanisms in lymphatic endothelial cell (LECs). Experimental approach: WMJ-S-001's effects on LEC proliferation, migration and invasion, as well as signaling molecules activation were analyzed by immunoblotting, flow-cytometry, MTT, BrdU, migration and invasion assays. We performed tube formation assay to examine WMJ-S-001's ex vivo anti-lymphangiogenic effects. Key results: WMJ-S-001 inhibited serum-induced cell proliferation, migration, invasion in murine LECs (SV-LECs). WMJ-S-001 reduced the mRNA and protein levels of survivin. Survivin siRNA significantly suppressed serum-induced SV-LEC invasion. WMJ-S-001 induced p53 phosphorylation and increased its reporter activities. In addition, WMJ-S-001 increased p53 binding to the promoter region of survivin, while Sp1 binding to the region was decreased. WMJ-S-001 induced p38 mitogen-activated protein kinase (p38MAPK) activation. p38MPAK signaling blockade significantly inhibited p53 phosphorylation and restored survivin reduction in WMJ-S-001-stimulated SV-LCEs. Furthermore, WMJ-S-001 induced survivin reduction and inhibited cell proliferation, invasion and tube formation of primary human LECs. Conclusions and Implications: These observations indicate that WMJ-S-001 may suppress lymphatic endothelial remodeling and reduce lymphangiogenesis through p38MAPK-p53-survivin signaling. It also suggests that WMJ-S-001 is a potential lead compound in developing novel agents for the treatment of lymphangiogenesis-associated diseases and cancer.

Enhancing production of lutein by a mixotrophic cultivation system using microalga Scenedesmus obliquus CWL-1.

This work studies a series of strategies in the production of lutein by Scenedesmus obliquus CWL-1 under mixotrophic cultivation. Our experimental results revealed that the optimal conditions associated with light-related strategies were 12 h light period followed by a 12 h dark period and blue to red light under mixotrophic cultivation. Under such conditions, the biomass, lutein content and lutein productivity were maximized to 9.88 (g/L), 1.78 (mg/g) and 1.43 (mg/L/day), respectively. Moreover, the assimilation of 4.5 g/L of calcium nitrate into S. obliquus CWL-1 increased the maximal biomass (12.73 g/L) and the highest maximal lutein productivity (3.06 mg/L/day), while the assimilation of 1.5 g/L of calcium nitrate yielded the highest maximal lutein content of 2.45 mg/g. The highest maximal lutein productivity of 4.96 (mg/L/day) was obtained when fed-batch fermentation was conducted, and this value was approximately 11-folds that obtained using the batch system.

Intermittent Parathyroid Hormone Injection Can Decrease Femoral Head Collapse in the Vascular Deprivation of Rat Femoral Head Model.

BACKGROUNDS: Intermittent parathyroid hormone (intermittent PTH) injection has been shown to improve osteogenesis. We hypothesized that intermittent PTH injection could stimulate osteogenesis during the early phase of vascular deprivation-induced femoral neck osteonecrosis in a rat model. MATERIALS AND METHODS: Eighteen Sprague-Dawley rats were divided into three groups (normal saline [CON], PTH 10 µg/kg [PTH-H], and PTH 1 µg/kg [PTH-L]) for 8 weeks by subcutaneous injection. All rats were sacrificed at postoperative 8 weeks, and all underwent a micro-computed tomography (µ-CT) examination for bone quality and quantity evaluation and histomorphometric analysis for microscopic histologic differences. RESULTS: Under µ-CT examination, both the PTH-H and PTH-L groups revealed less bone resorption than the control group. The PTH-H group had a better bone protective effect than the PTH-L group. Bone mineral density was increased in the PTH-H and PTH-L groups compared to the control group. The uninjured left femoral head was enlarged in both PTH groups. The histologic examination showed that both PTH groups had new bone and cartilage formation. The control group had only dead bone without any osteogenesis. CONCLUSION: Intermittent PTH injection could decrease bone resorption and improve bone density, compared to the control group, in vascular deprivation of the femoral head in a rat model. High-level intermittent PTH injection had a better effect than low-level intermittent PTH injection.

Exploring useful fermentation strategies for the production of hydroxyectoine with a halophilic strain, Halomonas salina BCRC 17875.

Hydroxyectoine, an ectoine derivative, is the most common compatible solute in halophilic microorganisms for resisting harsh environments. Compatible solutes can be utilized in fields such as cosmetics, medicine, and biochemistry. Moderately halophilic microorganisms produce much less hydroxyectoine as compared with ectoine. In this study, we first evaluate the effect of medium formulation (i.e., yeast extract (YE) medium and high yeast extract (HYE) medium) on hydroxyectoine production. In addition, an investigation of hydroxyectoine production by Halomonas salina under optimal conditions for vital factors (i.e., iron and α-ketoglutarate) and hydroxylase activity was also carried out. As a result, hydroxyectoine production was obviously elevated (0.9 g/L to 1.8 g/L) when the HYE medium was utilized. Furthermore, hydroxyectoine production further increased to 2.4 g/L when both the α-ketoglutarate and iron factors were added to the HYE medium in the early stationary phase. In addition, we found that ectoine hydroxylase activity increased more when a combination of iron and α-ketoglutarate was used than when either was used alone. The results showed that the alteration of iron and α-ketoglutarate clearly stimulated the expression of ectoine hydroxylase, which in turn affected hydroxyectoine synthesis. This study also showed that hydroxyectoine production was further raised from 2.4 g/L to 2.9 g/L when 50 mM of α-ketoglutarate and 1 mM of iron were added to the HYE medium. Ultimately, the experimental results showed using the optimal conditions further elevated the hydroxyectoine production yield to 2.90 g/L, which was over 3-fold higher than the best results obtained from the original medium.

Construction and co-cultivation of two mutant strains harboring key precursor genes to produce prodigiosin.

The biosynthesis of prodigiosin (PG) from Serratia marcescens involves the coupling of a bipyrrole, 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC), with a monopyrrole, 2-methyl-3-n-amyl-pyrrole (MAP), and formation of a linear tripyrrole (PG). We constructed mutant strains in which either the MBC biosynthesis by S. marcescens BMJ816 or the MAP biosynthesis by S. marcescens AMJ817. S. marcescens BMJ816 and AMJ817 confirmed that they lose the ability to synthesize PG when they are cultivated alone. An experiment was also conducted in which cultures of the two mutant strains were grown to the early exponential phase in a semi-defined medium, and one suspension culture was inoculated with the other. This approach yielded 103 mg/L PG. The findings suggest that the addition of precursors may enhance PG production by microorganisms.

Sintered dicalcium pyrophosphate treatment attenuates estrogen deficiency-associated disc degeneration in ovariectomized rats.

BACKGROUND: Estrogen deficiency is associated with musculoskeletal disorders. Sintered dicalcium pyrophosphate (SDCP) is a novel antiosteoporotic agent. In this study, we examined its use for restoration of bone quality and attenuation of disc degeneration in ovariectomy rats. METHODS: Sixty female Sprague Dawley rats were randomly divided into 3 groups, namely sham group undergoing sham surgery, ovariectomy (OVX) group receiving an equivalent volume of isotonic sodium chloride solution, and OVX/SDCP group orally administered with 0.25 mg/mL SDCP. Animals were sacrificed at 3 and 6 months post ovariectomy and lumbar vertebrae and intervertebral discs were harvested. Bone mineral density, micro-computed tomography analysis, and biomechanical testing were performed to assess bone quality. Histological analysis with hematoxylin and eosin, Alcian blue, and Masson's trichrome stain were conducted to determine disc degeneration. Immunohistochemistry and real-time PCR were carried out to measure the expressions of aggrecan, type I collagen, type II collagen, and MMP-1, MMP-3, and MMP-13. RESULTS: SDCP improved bone quality as observed by the results of increased bone mineral density and stiffness in OVX rats. The improvement in disc degeneration induced by estrogen withdrawal was associated with reduced gene expressions of MMPs and increased production of collagen type II. CONCLUSION: SDCP prevents osteoporosis and ameliorates disc degeneration in OVX rats. It represents a favorable therapeutic agent for osteoporotic and osteoarthritic conditions in clinical practice.

Effectiveness of Strontium Ranelate in the Treatment of Rat Model of Legg-Calve-Perthes Disease.

BACKGROUND: Legg-Calve-Perthes disease (LCPD) causes osteonecrosis of the femoral head (ONFH) by temporarily interrupting the blood supply in children. Even with potential toward bone regeneration and revascularization in LCPD, the prognosis depends on the deformity of femoral heads, and successful rate with the current treatments varies. Antiresorptive therapy such as bisphosphonate, which maintains mechanical stability of the femoral head by inhibiting necrotic bone resorption, has proven effective in animal models. However, concerns on simultaneous decline in bone turnover rate still leave room for improvement. Strontium ranelate with dual effect on inhibiting bone resorption and accelerating bone formation is presumed to be an ideal therapy for reserving sphericity of femoral heads in LCPD. MATERIALS AND METHODS: In this study of a rat model of ONFH, randomized groups of rats treated with strontium ranelate or normal saline are compared at different time points in analysis of radiological, histological, and bone morphometric changes. Gait analysis was also compared between the two groups. RESULTS: The group treated with strontium ranelate recovered their normal gait earlier than the control group did. Bone density, trabecular thickness, sphericity of the femoral head, and bone regeneration potential were also preserved in the strontium ranelate group. CONCLUSION: Strontium ranelate effectively prevented collapse of the ischemic femoral head and enhanced trabecular thickness in the rat model of LCPD. Hopefully, this preclinical experiment can improve the effectiveness of strontium ranelate treatment for pediatric ONFH.