Identification of Risk Factors for Primary Osteoporosis: The Role of Cervical Ligament Ossification.

BACKGROUND Long-term clinical practice has suggested a possible association between ossification of cervical ligament (OCL) and primary osteoporosis (POP). However, there is a lack of relevant research data. This study aimed to clarify the potential relationship between OCL and POP, and propose new strategies for preventing the onset of POP. MATERIAL AND METHODS The study involved 107 patients. The patients' diagnosis included OCL (ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and ossification of the nuchal ligament) and POP. Bone mineral density (BMD), types of OCL, types of ossification of posterior longitudinal ligament, age, sex, serum calcium, serum phosphorus, alkaline phosphatase, type I collagen amino-terminal extension peptide, type I collagen degradation products, osteocalcin N-terminal molecular fragments, 25-hydroxyvitamin D, and history of taking steroid drugs were collected. SPSS24.0 and GraphPad Prism 8 were used to obtain the risk factors for POP. RESULTS One-way analysis of variance found that OCL, ossification of posterior longitudinal ligament, alkaline phosphatase, and osteocalcin N-terminal molecular fragments had statistical significance on BMD of the femoral neck (P<0.05). The independent sample t test showed that patient sex had statistical significant effect on BMD (femoral neck) (P=0.036). Incorporating the above factors into multiple linear regression analysis, it was found that OCL, alkaline phosphatase, and osteocalcin N-terminal molecular fragments were risk factors affecting BMD of femoral neck (P<0.05). CONCLUSIONS OCL, osteocalcin N-terminal molecular fragments, and alkaline phosphatase are risk factors for POP.

Risk-adapted stereotactic body radiotherapy for patients with cervical spinal metastases.

Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard-risk patients were planned to receive 30 Gy (range 21-36) with median fractions of 3 (range 1-3) and high-risk patients 35 Gy (range 24-50) with median fractions of 5 (range 4-5) according to the spinal cord and esophagus dose constraints. The median follow-up time was 17.07 months (range 3.1-118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1-year and 2-year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1-4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk-adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.

First Indirect Drive Experiment Using a Six-Cylinder-Port Hohlraum.

The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of ∼222 eV for ∼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency η∼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (>1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.

Measurement of Time-Dependent Drive Flux on the Capsule for Indirectly Driven Inertial Confinement Fusion Experiments.

A new method for measuring the time-dependent drive flux at the hohlraum center is proposed as a better alternative to conventional wall-based techniques. The drive flux here is obtained by simultaneous measurement of the reemitted flux and shock velocity from a three-layered "cakelike" sample. With these two independent observables, the influence induced by the uncertainty of the material parameters of the sample can be effectively decreased. The influence from the closure of the laser entrance hole, which was the main challenge in conventional wall-based techniques, was avoided through localized reemitted flux measurement, facilitating drive flux measurement throughout the entire time history. These studies pave a new way for probing the time-dependent drive flux, for both cylindrical hohlraums and novel hohlraums with six laser entrance holes.

Recent advancement of decellularization extracellular matrix for tissue engineering and biomedical application.

BACKGROUND: Decellularized extracellular matrixs (dECMs) derived from organs and tissues have emerged as a promising tool, as they encompass the characteristics of an ideal tissue scaffold: complex composition, vascular networks and unique tissue-specific architecture. Consequently, their use has propagated throughout tissue engineering and regenerative medicine. dECM can be easily obtained from various tissues/organs by appropriate decellularization protocolsand is entitled to provide necessary cues to cells homing. METHODS: In this review, we describe the decellularization and sterilization methods that are commonly used in recent research, the effects of these methods upon biologic scaffold material are discussed. Also, we summarize the recent developments of recellularization and vascularization techniques in regeneration medicine. Additionally, dECM preservation methods is mentioned, which provides the basis for the establishment of organ bank. RESULTS: Biomedical applications and the status of current research developments relating to dECM biomaterials are outlined, including transplantation in vivo, disease models and drug screening, organoid, 3D bioprinting, tissue reconstruction and rehabilitation and cell transplantation and culture. Finally, critical challenges and future developing technologies are discussed. CONCLUSIONS: With the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.

Effect of cryoprotectants on rat kidney decellularization by freeze-thaw process.

To overcome the shortage of organ donors and morbidity and mortality caused by lifetime immunosuppression, development of a transplantable graft to permanently replace the organ function is required. This study is focused on the effects of a freeze-thaw process and cryoprotectants on the ultrastructure and composition of decellularization scaffolds. Results showed that cryoprotectants and freezing temperatures had significant effects on the decellularization scaffold. The vascular network integrity at -20 °C was better than that at -80 °C. For low-concentration cryoprotectants, 10% dimethyl sulfoxide and 5% trehalose could achieve a better balance between preserving the vascular tree and decellularization. For high-concentration cryoprotectants (vitrification solutions VS55 and VS83), the vascular network integrity was best because of the absence of freezing damage and ice-induced disruption of cells, but the decellularization effect was poor because the cells remained in the scaffold. Collagen, elastic fiber, protein, and mechanical properties of the scaffold could be retained after decellularization using the freeze-thaw method. Further studies and further optimization of the freeze-thaw decellularization protocol are necessary for clinical applications.

First Inertial Confinement Fusion Implosion Experiment in Octahedral Spherical Hohlraum.

In inertial confinement approaches to fusion, the asymmetry of target implosion is a major obstacle to achieving high gain in the laboratory. A recently proposed octahedral spherical hohlraum makes it possible to naturally create spherical target irradiation without supplementary symmetry control. Before any decision is made to pursue an ignition-scale laser system based on the octahedral hohlraum, one needs to test the concept with the existing facilities. Here, we report a proof-of-concept experiment for the novel octahedral hohlraum geometry on the cylindrically configured SGIII laser facility without a symmetry control. All polar and equatorial self-emission images of the compressed target show a near round shape of convergence ratio 15 under both square and shaped laser pulses. The observed implosion performances agree well with the ideal spherical implosion simulation. It also shows limitations with using the existing facilities and adds further weight to the need to move to a spherical port geometry for future ignition laser facilities.

Evaluation of solid state of rice flours produced by different milling processes using ATR-FTIR spectroscopy.

This study evaluated the influence of the milling process on solid state of rice flours according to water activity using ATR-FTIR. A band at 1740 cm-1 attributed to the C=O stretching of lipids was detected for crystalline samples, and it disappeared at a high aw range. The CH band at 2930 cm-1 of crystalline samples gradually shifted to a higher wavenumber with aw. This band of the α-formed and wet-milled samples shifted to higher wavenumbers above 0.8aw. A band due to OH stretching mode in the 3500-3000 cm-1 region did not shift with aw. The result obtained from IR spectra suggests that the parameter K calculated by Guggenheim-Anderson-de Boar model reflected not only the interaction between water molecules but also the changes of state in solids. Consequently, the results from this study provide insights about the adsorption properties of nonideal solids such as rice flour.

Effect of socket-shield technique on alveolar ridge soft and hard tissue in dogs.

AIM: To study the soft and hard tissue alterations of the alveolar ridge after socket-shield technique. MATERIALS AND METHODS: In four Beagle dogs, the following treatments (Tx) were randomly assigned to 32 extraction sockets: Tx1: blood clot; Tx2: Bio-Oss Collagen; Tx3: socket-shield technique and blood clot; Tx4: socket-shield technique and Bio-Oss Collagen. The width and height alterations of the buccal bone plate were calculated by CBCT scans. The dimensional alterations of the buccal aspect of the alveolar ridge at different time points were calculated by impressions using digital imaging analysis. The dogs were sacrificed for micro-CT and histologic analysis 3 months after surgery. RESULTS: Width, height and dimensional alterations of Tx3 and Tx4 were significantly lower than those of Tx1 and Tx2. Bone morphological parameters displayed no significant differences among four groups except for the trabecular thickness of Tx1 and Tx2. The quantity and quality of hard tissue containing the residual teeth of Tx3 and Tx4 were much greater than those of Tx1 and Tx2. CONCLUSIONS: Socket-shield technique may be beneficial in preserving the soft and hard tissue of the alveolar ridge, which is better than simple bone grafting in the extraction socket.

First Octahedral Spherical Hohlraum Energetics Experiment at the SGIII Laser Facility.

The first octahedral spherical hohlraum energetics experiment is accomplished at the SGIII laser facility. For the first time, the 32 laser beams are injected into the octahedral spherical hohlraum through six laser entrance holes. Two techniques are used to diagnose the radiation field of the octahedral spherical hohlraum in order to obtain comprehensive experimental data. The radiation flux streaming out of laser entrance holes is measured by six flat-response x-ray detectors (FXRDs) and four M-band x-ray detectors, which are placed at different locations of the SGIII target chamber. The radiation temperature is derived from the measured flux of FXRD by using the blackbody assumption. The peak radiation temperature inside hohlraum is determined by the shock wave technique. The experimental results show that the octahedral spherical hohlraum radiation temperature is in the range of 170-182 eV with drive laser energies of 71 kJ to 84 kJ. The radiation temperature inside the hohlraum determined by the shock wave technique is about 175 eV at 71 kJ. For the flat-top laser pulse of 3 ns, the conversion efficiency of gas-filled octahedral spherical hohlraum from laser into soft x rays is about 80% according to the two-dimensional numerical simulation.

A novel epidermal growth factor receptor inhibitor for treating lung cancer.

To investigate the effects of a novel synthetic epidermal growth factor receptor inhibitor, COMPOUND7809, on the inhibition of lung cancer growth in vitro and the underlying mechanisms, we treated three lung tumor cell lines (A549, SK-LU-1, and NCI-H23) with COMPOUND7809 and a Food and Drug Administration-approved epidermal growth factor receptor inhibitor gefitinib. Then, we examined cell growth in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell survival in a Cell Counting Kit-8 assay, and cell apoptosis by Annexin V flow cytometry in the presence of fluorouracil. We found that compared to gefitinib, COMPOUND7809 inhibited cell growth more potentially and induced more cell death in the presence of fluorouracil. Thus, our study demonstrates that COMPOUND7809 may be a promising epidermal growth factor receptor inhibitor for human lung cancer therapy.

Influence of Sanao Tang on urine volume and expression of aquaporin 2 in rats with respiratory function impairment induced by passive smoking and lipopolysaccharide.

OBJECTIVE: To investigate the effect of Sanao Tang (SAT) on urine volume and the expression of aquaporin- 2 (AQP2) in rats with lung dysfunction induced by passive smoking and lipopolysaccharide. METHODS: Totally 45 healthy Specific pathogen Free Wistar Rats were randomized into 3 groups: normal control group, model group and SAT group. A rat model of respiratory dysfunction induced by exposure to cigarette smoking and lipopolysaccharide (LPS). Lavage of decoction of the Chinese medicine was performed for rats in the SAT group. Anires 2005 System was used to analyze the pulmonary function. Urine of rats was collected through metabolism cage method. Enzyme-linked immunosorbent assay (ELISA) was used to determine content of antidiuretic hormone (ADH), angiotensin Ⅱ (AngⅡ), atrial natriuretic factor (ANP), endothelin 1 (ET-1), nitric oxide (NO) and prostaglandin E2 (PGE2) in serum, lung and kidney. The expression of AQP2 in rat renal tissue was determined with real-time fluorescence quantitative PCR (RT-PCR). RESULTS: (a) In comparison with the normal control, It was found that enforced vital capacity (FVC), 1-second forced expiratory volume/forced vital capacity% (FEV(1)/FVC%), 24 h urine volume content of NO and PGE2 were decreased, while AQP2mRNA level and content of ADH, Agn Ⅱ, ANP and ET-1 were increased in the model group with statistical significance (P < 0.05). (b) In comparison with the model group, It was found that FVC, FEV(1), FEV(1)/FVC%, 24 h urine volume, content of PGE2 and NO decreased, while AQP2mRNA level, content of ANP, ADH and Ang Ⅱ decreased in the SAT group with statistical significance (P < 0.05). CONCLUSION: SAT might effectively regulate the urine volume in the modeled rats; ADH, Ang Ⅱ, ANP, ET-1, NO and PGE2 might play an important role in the regulation on urine volume by lungs. This might be the mechanisms underpinning the function of lung governing water passage in terms of the theory of Traditional Chinese Medicine.

Comparison of MBM and ESD in the Treatment of Single Early Esophageal Cancer and Precancerous Lesions.

AIM: Esophageal cancer is a disease with high morbidity and mortality, exploring effective treatment methods is the key to the treatment of this disease. This study aims to compare the clinical efficacy and safety of multi-band mucosectomy (MBM) and endoscopic submucosal dissection (ESD) in the treatment of single early esophageal cancer (EEC) and precancerous lesions, and whether MBM can achieve better clinical effect as an effective treatment method. METHODS: The clinical data of 70 patients with EEC and precancerous lesions who were treated with MBM and ESD in the Fourth Affiliated Hospital of China Medical University from May 2021 to May 2023 and could be followed up were retrospectively analyzed. They were divided into two groups according to different treatment methods: MBM group (31 cases) and ESD group (39 cases). The general data, perioperative conditions, endoscopic treatment effect and pathological results of the two groups were compared. RESULTS: The duration of endoscopic treatment in MBM group was shorter than that in ESD group [36 (25~39) min vs 46 (41~57) min, p < 0.05], and there was no significant difference in the intraoperative bleeding rate between the two groups (12.90% vs 7.69%, p > 0.05). There was no significant difference in the rate of intraoperative perforation between the two groups (3.23% vs 7.69%, p > 0.05), and the hospitalization time in MBM group was shorter than that in ESD group [5 (4~7) days vs 8 (7~12) days, p < 0.05]. The hospitalization cost was less [2535 (2423~2786) dollars vs 4485 (3858~5794) dollars, p < 0.05]. No postoperative bleeding occurred in both groups. There was no statistically significant difference in postoperative stenosis rate between MBM group and ESD group (3.23% vs 12.82%, p > 0.05), and no statistically significant difference in postoperative local recurrence rate (12.90% vs 5.13%, p > 0.05). There was no significant difference in the rate of additional surgery (9.68% vs 2.56%, p > 0.05). The en bloc resection rate of MBM group was lower than that of ESD group (77.42% vs 97.44%, p < 0.05), but there was no significant difference in the complete resection rate between the two groups (87.10% vs 97.44%, p > 0.05). The postoperative pathological results of MBM group showed 13 cases of low-grade intraepithelial neoplasia (LGIN), 11 cases of high-grade intraepithelial neoplasia (HGIN), and 7 cases of canceration, while the postoperative pathological results of ESD group showed 10 cases of LGIN, 14 cases of HGIN, and 15 cases of canceration, with no statistical significance (p > 0.05). CONCLUSIONS: MBM and ESD are effective methods for the treatment of EEC and precancerous lesions. MBM has the advantages of short hospital stay, quick recovery and low cost. However, compared with MBM, ESD can improve the complete resection rate of the lesion, avoid the occurrence of positive incisal margin, and reduce the risk of secondary treatment and additional surgery.

Light irradiation changes the regulation pattern of BtCrgA on carotenogenesis in Blakeslea trispora.

CrgA has been shown to be a negative regulator of carotenogenesis in some filamentous fungi, while light irradiation is an inducible environmental factor for carotenoid biosynthesis. To clarify the relationship between CrgA and light-inducible carotenogenesis in Blakeslea trispora, the cis-acting elements of the btcrgA promoter region were investigated, followed by the analyses of correlation between the expression of btcrgA and carotenoid structural genes under different irradiation conditions. A variety of cis-acting elements associated with light response was observed in the promoter region of btcrgA, and transcription of btcrgA and carotenoid structural genes under different irradiation conditions was induced by white light with a clear correlation. Then, RNA interference and overexpression of btcrgA were performed to investigate their effects on carotenogenesis at different levels under irradiation and darkness. The analyses of transcription and enzyme activities of carotenoid structural gene, and accumulation of carotenoids among btcrgA-interfered, btcrgA-overexpressed, and wild-type strains under irradiation and darkness indicate that btcrgA negatively regulates the synthesis of carotenoid in darkness, while promotes the carotenogenesis under irradiation regardless of reduced or overexpression of btcrgA .

Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function.

Osteoporosis is a systemic disease characterized by an imbalance in bone homeostasis, where osteoblasts fail to fully compensate for the bone resorption induced by osteoclasts. Corylifol A, a flavonoid extracted from Fructus psoraleae, has been identified as a potential treatment for this condition. Predictions from network pharmacology and molecular docking studies suggest that Corylifol A exhibits strong binding affinity with NFATc1, Nrf2, PI3K, and AKT1. Empirical evidence from in vivo experiments indicates that Corylifol A significantly mitigates systemic bone loss induced by ovariectomy by suppressing both the generation and activation of osteoclasts. In vitro studies further showed that Corylifol A inhibited the activation of PI3K-AKT and MAPK pathways and calcium channels induced by RANKL in a time gradient manner, and specifically inhibited the phosphorylation of PI3K, AKT, GSK3 ß, ERK, CaMKII, CaMKIV, and Calmodulin. It also diminishes ROS production through Nrf2 activation, leading to a decrease in the expression of key regulators such as NFATcl, C-Fos, Acp5, Mmp9, and CTSK that are involved in osteoclastogenesis. Notably, our RNA-seq analysis suggests that Corylifol A primarily impacts mitochondrial energy metabolism by suppressing oxidative phosphorylation. Collectively, these findings demonstrate that Corylifol A is a novel inhibitor of osteoclastogenesis, offering potential therapeutic applications for diseases associated with excessive bone resorption.

K-shell photoabsorption edge of strongly coupled matter driven by laser-converted radiation.

The first observation of the K-shell photoabsorption edge of strongly coupled matter with an ion-ion coupling parameter of about 65 generated by intense x-ray radiation-driven shocks is reported. The soft x-ray radiation generated by laser interaction with a "dog bone" high-Z hohlraum is used to ablate two thick CH layers, which cover a KCl sample, to create symmetrical inward shocks. While the two shocks impact at the central KCl sample, a highly compressed KCl is obtained with a density of 3-5 times solid density and a temperature of about 2-4 eV. The photoabsorption spectra of chlorine near the K-shell edge are measured with a crystal spectrometer using a short x-ray backlighter. The redshift of the K edge up to 11.7 eV and broadening of 15.2 eV are obtained for the maximum compression. A comparison of the measured redshifts and broadenings with dense plasma calculations are made, and it indicates potential improvements in the theoretical description.

Predicting GPR40 Agonists with A Deep Learning-Based Ensemble Model.

Recent studies have identified G protein-coupled receptor 40 (GPR40) as a promising target for treating type 2 diabetes mellitus, and GPR40 agonists have several superior effects over other hypoglycemic drugs, including cardiovascular protection and suppression of glucagon levels. In this study, we constructed an up-to-date GPR40 ligand dataset for training models and performed a systematic optimization of the ensemble model, resulting in a powerful ensemble model (ROC AUC: 0.9496) for distinguishing GPR40 agonists and non-agonists. The ensemble model is divided into three layers, and the optimization process is carried out in each layer. We believe that these results will prove helpful for both the development of GPR40 agonists and ensemble models. All the data and models are available on GitHub. (https://github.com/Jiamin-Yang/ensemble_model).

Droplet Generation, Vitrification, and Warming for Cell Cryopreservation: A Review.

Cryopreservation is currently a key step in translational medicine that could provide new ideas for clinical applications in reproductive medicine, regenerative medicine, and cell therapy. With the advantages of a low concentration of cryoprotectant, fast cooling rate, and easy operation, droplet-based printing for vitrification has received wide attention in the field of cryopreservation. This review summarizes the droplet generation, vitrification, and warming method. Droplet generation techniques such as inkjet printing, microvalve printing, and acoustic printing have been applied in the field of cryopreservation. Droplet vitrification includes direct contact with liquid nitrogen vitrification and droplet solid surface vitrification. The limitations of droplet vitrification (liquid nitrogen contamination, droplet evaporation, gas film inhibition of heat transfer, frosting) and solutions are discussed. Furthermore, a comparison of the external physical field warming method with the conventional water bath method revealed that better applications can be achieved in automated rapid warming of microdroplets. The combination of droplet vitrification technology and external physical field warming technology is expected to enable high-throughput and automated cryopreservation, which has a promising future in biomedicine and regenerative medicine.

Determination of the hohlraum M-band fraction by a shock-wave technique on the SGIII-prototype laser facility.

The proposal of simultaneously determining the hohlraum peak radiation temperature T(R) and M-band fraction f(M) by shock velocity measurement technique [Y. S. Li et al. Phys. Plasmas 18, 022701 (2011)] is demonstrated for the first time in recent experiments conducted on SGIII-prototype laser facility. In the experiments, T(R) and f(M) are determined by using the observed shock velocities in Al and Ti. For the Au hohlraum used in the experiments, T(R) is about 160 eV and f(M) is around 4.3% under a 1 ns laser pulse of 2 kJ. The results from this method are complementary to those from the broadband x-ray spectrometer, and the technique can be further used to determine T(R) and f(M) inside an ignition hohlraum.

[Preparation of tissue and organ decellularized scaffolds: a review].

Decellularized extracellular matrix (dECM) is designed to remove cells that cause immune rejection and retain the original tissue structure and composition. Since its structure and composition are similar to the original tissues and organs, it has attracted extensive attention in tissue engineering and biomedicine applications, and has become a promising tissue engineering material. dECM can be easily obtained from tissues and organs by appropriate decellularization methods. Here, we summarized the commonly used decellularization methods and reviewed the sterilization, cross-linking and storage methods of decellularized scaffold. In addition, we summarized the latest applications and developments of dECMs obtained from different tissues/organs in tissue engineering and biomedicine. Finally, we discussed the present challenges of dECM biomaterials and prospected future perspectives. With the development of tissue engineering and regenerative medicine technology, dECM biomaterials are expected to become a gold scaffold in the field of biomedicine and will receive wide applications.