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Abstract Background Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH. Methods In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed. Results Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway. Conclusion Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment.

Background: Osteoarthritis (OA) is a chronic and degenerative condition that persists and progresses over time. Sipeimine (Sip), a steroidal alkaloid derived from Fritillariae Cirrhosae Bulbus, has attracted considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, and anti-cancer characteristics. However, Sip's effects on OA and its mechanism still need further research. Methods: This study utilized network pharmacology to identify initial targets for Sip. Functional associations of Sip in OA were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing a list of targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis assessed pathways linked to Sip's therapeutic efficacy in OA. Molecular docking techniques explored Sip's binding affinity with key targets. In vitro experiments assessed Sip's impact on lipopolysaccharide (LPS)-induced pro-inflammatory factors and its protective effects on collagen-II and aggrecan degradation within the extracellular matrix (ECM). Western blotting and fluorescence analyses were conducted to determine Sip-mediated signaling pathways. Moreover, in vivo experiments using a mouse OA model validated Sip's therapeutic efficacy. Results: The results from network pharmacology revealed a total of 57 candidate targets for Sip in OA treatment. GO enrichment analysis demonstrated a robust correlation between Sip and inflammatory response, response to LPS and NF-κB-inducing kinase activity in OA. KEGG enrichment analysis highlighted the significance of NF-κB and PI3K-AKT pathways in Sip's therapeutic potential for OA. Furthermore, molecular docking results demonstrated Sip's robust binding affinity with p65 and PI3K. In vitro experiments demonstrated Sip's effectively suppressed the expression of pro-inflammatory factors induced by LPS, such as COX-2, iNOS, IL-1β, and IL-18. Besides, Sip counteracted the degradation of collagen-II and aggrecan within the ECM and the expression of MMP-13 and ADAMTS-5 mediated by LPS. The safeguarding effects of Sip were ascribed to its inhibition of PI3K/AKT/NF-κB pathway and NLRP3 inflammasome mediated pyroptosis. Additionally, in vivo experiments revealed that Sip could alleviate the subchondral remodeling, cartilage degeneration, synovitis as well as ECM degradation a mouse model of OA. Conclusion: Sip exhibited potential in attenuating OA progression by suppressing the PI3K/AKT/NF-κB pathway, consequently inhibiting the activation of NLRP3 inflammasome and pyroptosis. The translational potential statement: The translational potential of this articleThis study provides a biological rationale for the use of Sip as a potential candidate for OA treatment, provide a new concept for the cartilage targeted application of natural compounds.

In order to investigate the tensile properties of basalt fibre reinforced recycled aggregate concrete (BFRAC), the axial tensile tests were carried out on BFRAC specimens using the concrete axial tensile testing device. The effects of basalt fibre (BF) content and recycled aggregate replacement rate on the tensile properties of BFRAC were quantitatively investigated, and the tensile damage mechanism of BFRAC was analysed. The following conclusions were drawn: The volume fraction of BF had the most prominent effect on the axial tensile properties of BFRAC. The axial tensile strength and peak tensile strain of BFRAC both showed the change rule of first increasing and then decreasing with the increase of BF volume fraction. The replacement rate of recycled aggregate is negatively correlated with the tensile properties of BFRAC. The larger the replacement rate, the worse the tensile properties of BFRAC. When the replacement rate of recycled aggregate is 30 % and the volume fraction of BF is 0.3 %, the tensile properties of BFRAC are better, as well as its economic and environmental performance. The axial tensile strength and peak tensile strain were 2.08 MPa and 114 × 10−6, respectively. BFRAC exhibits the toughening and crack arresting effect of BF, and the crack development is relatively slow, showing more obvious plastic damage characteristics.

Abstract Background Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. Result This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. Conclusion This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.

Abstract Conducting research on the fatigue performance of concrete materials is of great significance for the anti fatigue design of concrete structures. Currently, indirect tensile or compressive strength tests are commonly used to study the fatigue performance of basalt fiber reinforced concrete, but there is little research on its fatigue performance under direct tensile conditions. Using a fatigue testing machine and a self-developed concrete axial tensile device, direct tensile fatigue tests of basalt fiber reinforced concrete were conducted under different fiber content and stress levels. Based on fatigue test data, the entire fatigue tensile process of basalt fiber reinforced concrete was analyzed, and the effects of fiber content and stress level on the fatigue life of concrete specimens were explored. Strain fatigue life curves of concrete with different fiber content were plotted. The experimental results indicate that the failure mode of basalt fiber reinforced concrete under cyclic loading is brittle failure; with the increase of basalt fiber content, the fatigue life of concrete first increases and then decreases. When the fiber content is 0.3%, the fatigue life of basalt fiber concrete is the highest compared to the benchmark concrete. When the fiber content is the same, the fatigue life of concrete decreases with the increase of stress level. The fatigue deformation process of basalt fiber reinforced concrete can be divided into three stages: the stage of fast strain growth, the stage of uniform strain growth, and the stage of rapid strain growth.

The mechanical properties of polyethylene fibre reinforced cementitious composites (PE-ECC) and polyethylene fibre-calcium carbonate whisker reinforced cementitious composites (PECW-ECC) were tested after exposure to different temperatures. And the microstructure changes of ECCs were observed by scanning electron microscope. The results showed the compressive and tensile strengths of PE-ECC and PECW-ECC tended to increase and then decrease with the increase of exposure temperature. The incorporation of CW improved the mechanical properties of PE-ECC to a certain extent. At the same exposure temperature, the compressive and tensile strengths of PECW-ECC are better than that of PE-ECC, and the plastic deformation capacity is also better than that of PE-ECC. The reason is that CW can be tightly bonded with the matrix material, and it has a filling effect on matrix defects, a bridging effect on the microscopic cracks, and a deflecting effect on the microscopic cracks.

Abstract Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

Abstract Background Steroid-induced avascular necrosis of the femoral head (SANFH) is characterized by osteoblast apoptosis, leading to a loss of bone structure and impaired hip joint function. It has been demonstrated that erythropoietin (EPO) performs a number of biological roles. Objective We examined the effects of EPO on SANFH and its regulation of the STAT1-caspase 3 signaling pathway. Method In vitro, osteoblasts were treated with dexamethasone (Dex) or EPO. We identified the cytotoxicity of EPO by CCK-8, the protein expression of P-STAT1, cleaved-caspase9, cleaved-caspase3, Bcl-2, BAX, and cytochrome c by Western blotting, and evaluated the apoptosis of osteoblasts by flow cytometry. In vivo, we analyzed the protective effect of EPO against SANFH by hematoxylin and eosin (H&E), Immunohistochemical staining, and Micro-computed tomography (CT). Results In vitro, EPO had no apparent toxic effect on osteoblasts. In Dex-stimulated cells, EPO therapy lowered the protein expression of BAX, cytochrome c, p-STAT1, cleaved-caspase9, and cleaved-caspase3 while increasing the expression of Bcl-2. EPO can alleviate the apoptosis induced by Dex. In vivo, EPO can lower the percentage of empty bone lacunae in SANFH rats. Conclusion The present study shows that EPO conferred beneficial effects in rats with SANFH by inhibiting STAT1-caspase 3 signaling, suggesting that EPO may be developed as a treatment for SANFH.

Abstract In order to study the axial tensile properties of polypropylene fiber reinforced concrete, an axial tensile test device for concrete is developed in this paper. The device is composed of three parts: rigid frame, spherical hinge and puller, and specimen fabrication part. The test device can accurately measure the tensile strength and peak tensile strain of concrete, and perfectly solves the eccentricity problem of concrete specimens under tension. It can measure the post peak segment tensile strain, such that the whole process tensile stress–strain curve can be obtained. The axial tensile test of polypropylene fiber concrete was carried out using the above test device, and the results show that the tensile strength of concrete can be clearly improved by adding polypropylene fiber, which makes the tensile failure of concrete show certain plastic characteristics. The test results show that with the increase in fiber content, the tensile strength of concrete increases first and then decreases. The effects of polypropylene fiber content and curing age on the tensile properties of concrete were studied and the optimum polypropylene fiber content was determined. When the fiber content is 0.9 kg/m3, the tensile strength of concrete reaches the maximum value. The splitting tensile test of concrete under the same condition was carried out simultaneously. The damage phenomenon and test results of the axial tensile test and splitting tensile test of concrete were compared and analyzed, and the applicability of the new developed device in the concrete axial tensile test was verified.

Objective(s): Recently, studies on microRNAs (miRNAs) and their targets and related genes have provided new therapeutic opportunities for controlling intervertebral disc degeneration (IDD). We aimed to investigate the effects of miR-148a-3p overexpression on IDD progression.Materials and Methods: This study used microRNA microarrays to analyze key regulators of IDD. Q-PCR was used to verify the IL-1β-induced down-regulation of miR-148a-3p expression both in nucleus pulposus (NP) tissues of IDD patients and in degenerated NP cells (NPCs) of rats. Rat NPC micromass cultures and ex vivo intervertebral disc (IVD) culture models were established, and histological staining was performed to verify the effect of miR-148a-3p on the general morphology and proteoglycan and collagen contents of IVDs. In addition, q-PCR and western blotting analyses were performed to examine the expression of ECM molecules and matrix-degrading enzymes. A luciferase reporter assay was used to confirm the target genes of miR-148a-3p.Results: Our data revealed that miR-148a-3p was down-regulated in IDD. Overexpression of miR-148a-3p had no effect on ACAN or COL2A1 gene expression but decreased MMP3, MMP13, and ADAMTS5 gene expression. The matrix deposited by miR-148a-3p-overexpressing rat NPCs contained high levels of proteoglycans and collagen. The ex vivo experiments verified that agomiR-148a-3p alleviated the NPC matrix degradation induced by IL-1β. A luciferase reporter assay confirmed that miR-148a-3p directly targeted ADAMTS5 and MMP13.Conclusion: We proved that miR-148a-3p can attenuate ECM loss and protect NP function by inhibiting matrix-degrading enzymes.

Abstract Bone metabolic homeostasis is largely dependent on the dynamic balance between osteoblasts and osteoclasts. MicroRNAs (miRNAs) play critical roles in regulating bone metabolism. In this study, we explored the role of a new miRNA (miR-148a) in osteoporosis. We compared the bone phenotype between miR-148a knockout (KO) mice and the wild-type (WT) littermates. We found miR-148a KO mice exhibited an increased bone mass phenotype and decreased osteoclastogenesis compared to the WT group. In vitro, miR-148a overexpression promoted osteoclastogenesis and bone resorption function. Mechanistically, NRP1 was identified as a novel direct target of miR-148a, and NRP1 silencing reversed the effect of miR-148a knockout. In OVX and calvarial osteolysis models, miR-148a KO protects mice against excessive bone resorption, while miR-148a agomiR/AAV-shNRP1 accelerates pathologic bone loss. Finally, the miR-148a level was found to be positively correlated with β-CTX in postmenopausal osteoporosis (PMOP) serum specimens. In summary, our findings revealed that miR-148a genetic deletion ameliorates bone loss under physiological and pathological conditions by targeting NRP1. In osteoclast-related bone metabolic diseases such as PMOP, miR-148a may be an attractive therapeutic target in the future.

Abstract Background Due to post-cleavage residence of the Cas9-sgRNA complex at its target, Cas9-induced DNA double-strand breaks (DSBs) have to be exposed to engage DSB repair pathways. Target interaction of Cas9-sgRNA determines its target binding affinity and modulates its post-cleavage target residence duration and exposure of Cas9-induced DSBs. This exposure, via different mechanisms, may initiate variable DNA damage responses, influencing DSB repair pathway choices and contributing to mutational heterogeneity in genome editing. However, this regulation of DSB repair pathway choices is poorly understood. Results In repair of Cas9-induced DSBs, repair pathway choices vary widely at different target sites and classical nonhomologous end joining (c-NHEJ) is not even engaged at some sites. In mouse embryonic stem cells, weakening the target interaction of Cas9-sgRNA promotes bias towards c-NHEJ and increases target dissociation and reduces target residence of Cas9-sgRNAs in vitro. As an important strategy for enhancing homology-directed repair, inactivation of c-NHEJ aggravates off-target activities of Cas9-sgRNA due to its weak interaction with off-target sites. By dislodging Cas9-sgRNA from its cleaved targets, DNA replication alters DSB end configurations and suppresses c-NHEJ in favor of other repair pathways, whereas transcription has little effect on c-NHEJ engagement. Dissociation of Cas9-sgRNA from its cleaved target by DNA replication may generate three-ended DSBs, resulting in palindromic fusion of sister chromatids, a potential source for CRISPR/Cas9-induced on-target chromosomal rearrangements. Conclusions Target residence of Cas9-sgRNA modulates DSB repair pathway choices likely through varying dissociation of Cas9-sgRNA from cleaved DNA, thus widening on-target and off-target mutational spectra in CRISPR/Cas9 genome editing.

Objective The aim of this study was to compare the radiological features of intravertebral clefts (IVC) between Kümmell disease (KD) and acute osteoporotic vertebral compression fracture (OVCF). Materials and Methods This is a retrospective study. A total of 79 patients with IVC from January 2014 to December 2018 were included in this study. There were 22 men and 57 women, with an average of 73.5 years. Based on the exact time interval from injury to treatment and the pathological examination results, the patients were divided into KD group (44 patients) and acute OVCF group (35 patients). The two groups were compared by the margin sclerosis of IVC, vertebra and pedicle ossification, stress fracture of the spinous process, paravertebral callus, the shape of IVC, cleft in the adjacent disc, and flatness of IVC's margin from plain radiographs and computed tomography (CT). The two groups were compared by the IVC content, double‐line sign, and signal of fracture vertebral from their magnetic resonance imaging (MRI). Results There were no significant differences in sex, age, and fracture distribution between the KD group and the acute OVCF group. IVC was present in both the KD group and the acute OVCF group. Six radiological features were only present in the KD group, including sclerosis of the cleft margin (95.5%, 42/44), ossification of the fractured vertebrae (100%, 44/44), ossification of the pedicle (31.8%, 14/44), double‐line sign (27.3%, 12/44), stress fracture of the spinous process (13.6%, 6/44), and even formation of paravertebral callus (18.2%, 8/44). Although there were statistical differences in the other four radiological features of content of IVC (P = 0.02), cleft sign in adjacent intervertebral disc (P

ObjectiveWe evaluated the effect of a novel modified OLIF technique (anteroinferior psoas approach, AIPA) for anterior decompression reconstruction in lumbar burst fractures, and compared the clinical, radiological outcomes and approach-related complications with the mini-open, lateral transpsoas approach (LTPA).MethodsFrom March 2016 to November 2019, 68 patients with lumbar burst fractures underwent one-stage monosegmental posterior/anterior surgery from L1–L4 segments. 35 patients included in AIPA and 33 patients in LTPA group underwent anterior decompression reconstruction. The clinical, radiological and functional evaluation outcomes were recorded during the 16–60 months follow-up period.ResultsAt the latest follow up, neurological state of one or more ASIA grades were achieved in AIPA (90.9%) and LTPA group (94.9%). No significant differences were noted between the two groups regarding preoperative and postoperative Cobbs angle. The surgery time (192.29 vs. 230.47 min, P = 0.02) in AIPA group was better compared with LTPA. The AIPA showed better improvement on Oswestry Disability Index (43.4% vs. 60.8%, P

Background Circulating tumor cells (CTCs) can survive in the circulation and return to primary tumors through a self-seeding process. However, the mechanisms underlying CTCs escape from natural killer (NK) cell-mediated immune surveillance remain unclear.Method Self-seeded tumor cells were isolated and characterized using a modified contralateral seeding model. A comparison of transcriptional profiles was performed between the parental cells and self-seeded cells. The molecular mechanism of self-seeded tumor cells escaping from NK cell was demonstrated through in vitro experiments and verified in a CTC-mimicking in vivo model. Then, the expression level of key protein mediating CTCs immune escape was detected in 24 paired primary and recurrent tumor samples of patients with oral cancer by the immunohistochemical method.Result Self-seeded cells displayed resistance to NK cell-mediated lysis and a higher tumor seeding ability than their parental cells. Elevated expression levels of the CDH2 gene and its protein product, N-cadherin were found in self-seeded cells. NK cells secreted cytokines, and fluid shear stress facilitated N-cadherin release by promoting A disintegrin and metalloprotease 10 (ADAM10) translation or converting the precursor ADAM10 to the mature form. Soluble N-cadherin triggered NK cell functional exhaustion by interacting with the killer cell lectin-like receptor subfamily G member 1 (KLRG1) receptor and therefore protected tumor cells from NK cell killing in the circulation. In vivo experimental results showed that overexpression of N-cadherin promoted tumor self-seeding and facilitated the survival of CTCs. Compared with primary tumors, N-cadherin expression was significantly increased in matched recurrent tumor tissues.Conclusion Together, our findings illustrate an unknown mechanism by which CTCs evaded NK cell-mediated immune surveillance, and indicate that targeting N-cadherin is an effective strategy to prevent CTCs from homing to primary tumor.

Tetrahydropalmatine (dl-THP) demonstrates an analgesic effect in animal models of neuropathic and inflammatory pain, however, the underlying mechanisms of its pharmacological action within the spinal cord remains unclear. Both P2X3 receptor and TRPV1 are associated with the development and progression of such neuropathic and inflammatory pain. Here, we found that both pre-treatment and post-treatment with dl-THP could attenuate Bee Venom (BV)-induced persistent spontaneous pain-related behaviors in rats. Further, the dl-THP also exerted both preventive and therapeutic analgesic effects in BV-induced primary thermal and mechanical pain hypersensitivity as well as in mirror-image thermal pain hypersensitivity. The Rota-Rod treadmill test revealed that the dl-THP administration did not alter the rats’ motor coordinating performance. The TRPV1 and P2X3 receptor proteins increased markedly in the spinal cord of the rats following s.c. BV injection, which was significantly suppressed by dl-THP. These results suggest that dl-THP exerts a robust antihyperalgesia effect through down-regulation of P2X3 receptors and TRPV1 in inflammatory pain, providing a scientific basis for the translation of dl-THP treatment in clinics.

Induction chemotherapy in oral squamous cell carcinoma is a controversial issue in clinical practice. To investigate the evolution of cancer cells and tumor microenvironment (TME) response to chemotherapy in oral squamous cell carcinoma, single-cell transcriptome analysis was performed in a post-chemotherapy squamous cell carcinoma located in oral cavity. The main cell types were identified based on gene expression patterns determined using dimensionality reduction and unsupervised cell clustering. Non-negative matrix factorization clustering of the gene expression of Cancer-associated fibroblasts (CAFs) and macrophages was performed. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis were performed to explore significant functional pathways. CellPhoneDB and NicheNet were used to detect the intercellular communication between cell types. CAFs were divided into “inflammatory CAFs,” “antigen-presenting CAFs” and “myofibroblastic CAFs.” Three classic subgroups of tumor-associated macrophages (TAMs) were detected, namely C1Q (+), FCN1 (+) and SPP1(+) TAMs. The inflammatory cytokine expression is elevated, and several molecular pathways, such as PI3K/Akt/mTORC1, TNF-α via NFκB, TGF-β, IL-6/JAK2/STAT3 and CXCL12/CXCR4 axis associated with epithelial-mesenchymal transition were enriched in TME. Also, CD74-MIF/COPA/APP interactions were expressed in TME of oral squamous cell carcinoma after chemotherapy. The results revealed the characteristics of TME in post-chemotherapy oral squamous cell carcinoma at single-cell transcriptome level, providing new insights and clues for further investigation.

Abstract LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages.

High-purity titanium has been subjected to dynamic compression with a strain rate of 103 s−1 to activate {112-2} and {112-4} contraction twins. Electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), and high-resolution TEM (HRTEM) were performed to observe the morphologies and twin boundaries of the contraction twins. The results show that {112-2} twins are the predominant twinning mode, as well as the formation of {112-4} twins due to the change in local stress state at the intersection region of {112-2} twin variants or {112-2} twin and grain boundary. The TEM and HRTEM observations reveal that (0001)‖(1122-) facets and (0001)‖(1121-) facets formed along the {112-2} and {112-4} twin boundaries, respectively. According to the theory of interfacial defects, the propagation of the {112-2} twin boundary was discussed with (b3, 3h{112-2}) and (b1, h{112-2}) twinning disconnections, as well as the growth process of the {112-4} twin boundary.

Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of studies have suggested that intracellular reactive oxygen species (ROS) are strongly associated with osteoclastogenesis. As a novel angiotensin (Ang) II receptor blocker (ARB), azilsartan was reported to be associated with the inhibition of intracellular oxidative stress processes. However, the relationship between azilsartan and osteoclastogenesis is still unknown. In this study, we explored the effect of azilsartan on ovariectomy-induced osteoporosis in mice. Azilsartan significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, and Ctsk) in vitro. Furthermore, azilsartan reduced RANKL-induced ROS production by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, azilsartan inhibited the activation of MAPK/NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of azilsartan on MAPK/NF-κB signaling pathways. Consistent with the in vitro data, azilsartan administration ameliorated ovariectomy (OVX)-induced osteoporosis, and decreased ROS levels in vivo. In conclusion, azilsartan inhibited oxidative stress and may be a novel treatment strategy for osteoporosis caused by osteoclast overactivation.

A 27-year-old patient with azoospermia and low intelligence was reported having a rare karyotype 47,XYY,dup(13q12.11),t(4;9)(q21.1;q22.3),r(21)(p12q22.3). Clinical genetic tests, including next-generation sequencing (NGS), karyotyping, fluorescence in situ hybridization (FISH), and azoospermia factor (AZF) microdeletions, were conducted. The results showed that (1) one copy of chromosome 21 lost a short arm and appeared as a marker, but subsequent detection confirmed that it was a ring 21; (2) there was a reciprocal translocation between chromosome 4 and chromosome 9; (3) NGS revealed a duplication of 0.3 Mb on 13q12.11 and two Y chromosomes; (4) the Y chromosome showed no AZF microdeletions; and (5) FISH confirmed the two Y chromosomes. To our knowledge, this is the first reported case with rare karyotype, combined with four abnormal chromosomal changes simultaneously. Because no Online Mendelian Inheritance in Man genes were found in duplication fragment on 13q12.11, this duplication is not associated with low intelligence.

A young boy with a facial abnormality was brought to our genetics clinic. Physical examination found bilateral cryptorchidism. Several clinical genetic tests, including chromosome microarray analysis (CMA), karyotyping, and azoospermia factor (AZF) microdeletions on the Y chromosome, were used to identify the genetic basis for this abnormality. The karyotype showed a duplication of the chromosome 2q35q37.3 fragment attached to chromosome 9(p24); CMA revealed 2q35q37.3(220,558,895-243,006,013)x3; the Y chromosome showed no AZF microdeletions; and the parent karyotypes were normal. Surgery has been planned to correct cryptorchidism a year after the original examination. A similar case was found previously.

Objective: This study aimed to conduct a systematic review of literature comparing the clinical effectiveness and safety between anterior reconstruction (AR) and posterior osteotomy (PO) in the treatment of Kümmell's disease with neurological deficits. Methods: We systematically reviewed the literature in PubMed, EMBASE, Cochrane Database of Systematic Reviews, and the Web of Science for “spin*,” “surg*,” “Kümmell's disease,” “Kummell's disease,” “Kummell disease,” “vertebral osteonecrosis,” “vertebral pseudarthrosis,” “intravertebral vacuum cleft,” “delayed vertebral collapse,” and “compression fracture nonunion”. Quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method. Results: A total of 10 publications involving 268 Kümmell's disease patients with neurological deficits were included in this review, with 7 studies of low- or very low-quality. There were 37.7% and 62.3% of patients receiving AR and PO, respectively. For clinical outcomes, AR group showed no significant differences in pain, neurological dysfunction, and imaging outcome improvements compared with patients who underwent PO. However, the incidence of implant-related complications including loose screw, screw fracture, screw disconnection, and plate dislodgment, was higher in AR group compared with PO group (21.6% vs. 14.3%). As another major complication, AR group more often required a second surgery. Conclusion: This systematic review demonstrated that both AR and PO could improve pain, neurological dysfunction and imaging outcomes. However, serious comorbidities, multilevel corpectomies and/or severe osteoporosis highly required PO. Design discrepancies were found in the current studies, further higher-quality studies are warranted. Level of evidence: Level III, therapeutic study. Keywords: Kümmell's disease, Neurological deficits, Anterior reconstruction, Posterior osteotomy, Postoperative outcomes, Systematic review

This meta-analysis was designed to elucidate whether preoperative signal intensity changes could predict the surgical outcomes of patients with cervical spondylosis myelopathy on the basis of T1-weighted and T2-weighted magnetic resonance imaging images. We searched the Medline database and the Cochrane Central Register of Controlled Trials for this purpose and 10 studies meeting our inclusion criteria were identified. In total, 650 cervical spondylosis myelopathy patients with (+) or without (-) intramedullary signal changes on their T2-weighted images were examined. Weighted mean differences and 95g% confidence intervals were used to summarize the data. Patients with focal and faint border changes in the intramedullary signal on T2 magnetic resonance imaging had similar Japanese Orthopaedic Association recovery ratios as those with no signal changes on the magnetic resonance imaging images of the spinal cord did. The surgical outcomes were poorer in the patients with both T2 intramedullary signal changes, especially when the signal changes were multisegmental and had a well-defined border and T1 intramedullary signal changes compared with those without intramedullary signal changes. Preoperative magnetic resonance imaging including T1 and T2 imaging can thus be used to predict postoperative recovery in cervical spondylosis myelopathy patients.

Background: This study aims to investigate the spectrum and frequency of phenylalanine hydroxylase (PAH) gene mutations and the power to prenatally diagnose phenylketonuria (PKU) patients in Shaanxi, China. Methods: Polymerase chain reaction (PCR) and DNA sequencing analyses were performed to examine the PAH gene in 33 PKU patients and seven amniotic fluid samples. Thirty-four pathogenic variants were indicated in all 63 alleles, in which two probands carried three variants. Results: Pedigree analysis suggested that the [c.158G>A([p. R53H)][IVS7+2T>A] mutation was located at the same chromatid. However, there was a controversial viewpoint that thought the c.158G>A(p.R53H) variant was a polymorphism in the Chinese. We also found one novel indel mutation and identified the c.59_60delAGinsCC mutation of the PAH gene for the very first time. The spectrum of the PAH mutations in Shaanxi Province were similar to that among China's population. Based on the results of PAH gene analysis, we further performed prenatal genetic diagnoses for seven PKU families. All foetuses were definitively diagnosed, and their parents were provided with genetic counselling. Conclusions: PAH gene analysis is a crucial method for PKU diagnosis and prenatal genetic prognosis, even though many uncommon mutations would affect the analysis and diagnosis of genetic abnormalities. [ABSTRACT FROM AUTHOR]

Surface plasmon resonance (SPR) is a sensitive, rapid, simple and low cost method for detection of biological molecules. In this study, SPR technology with alkaline phosphatase as a probe was utilized to measure DNA strand breaks induced by 60Co gamma rays. The doses were from 0.01-10 Gy with a dose rate of 0.1 Gy/min. The results demonstrate that the SPR technology can be used to estimate strand breaks of calf thymus DNA. SPR signals of the calf thymus DNA samples increased with increasing gamma ray doses and the relationship of y = sqrt (3297 x + 582.6) (r = 0.99) between the SPR signal and gamma dose was obtained. Estimation of DNA strand breaks in irradiated lymphocytes by SPR also demonstrated an increase in SPR signal with increasing dose and the exponential relationship of y = 169.43 3 (1 - exp-0.89x) (r = 0.93) was obtained. The initial yield of the SPR signal is about 150.79 mdeg ⋅ Gy-1 and compared to the sensitivity of 0.05 Gy achieved by the neutral single cell gel electropho-resis (SCGE), the SPR-based assay of DNA strand breaks was found to be more sensitive (0.02 Gy). We therefore propose that SPR technology with alkaline phosphatase as the probe is a sensitive, simple and quick method for detection of DNA strand breaks in gamma-irradiated lymphocytes. [ABSTRACT FROM AUTHOR]

Even though serum iron is a commonly used parameter in iron metabolism, it has not yet been applied for biological dosimetry purpose. A new biological dosimeter based on serum iron has been developed in this work. Serum iron levels in mice subjected to gamma rays from a 60Co source were detected with the use of ferrous. The doses are from 0.2-7 Gy with a dose rate of 0.2 Gy/min. The results demonstrate that serum iron level increases with increasing dose. The detection limit based on serum iron has a lower limit of dose detection of about 0.5 Gy and the maximal increase of serum iron observed is maintained 4 h after γ irradiation. Therefore the best suggested time for blood collection is within 4 h after γ irradiation. Two dose-response relationships were observed with both according to degrees of the increase of serum iron levels and different intervals after γ irradiation. The first is a linear relationship of y = 0.98x + 6.76 (r = 0.98) obtained 10 min after γ irradiation; the second is the linear quadratic relationship of y=-0.07x² + 1.02x + 6.45 (r = 0.99) obtained 7 days after ² irradiation. The absorbed doses of mice estimated with the use of both these two dose-response relationships were close to the actual dose of 1 Gy. It is concluded that serum iron is a quick, simple and sensitive biomarker for early assessment of the absorbed dose of mice. [ABSTRACT FROM AUTHOR]

Human pancreatitis-associated protein was identified in pathognomonic lesions of Alzheimer disease, a disease characterized by the presence of filamentous protein aggregates. Here, we showed that at physiological pH, human pancreatitis-associated protein forms non-Congo Red-binding, proteinase K-resistant fibrillar aggregates with diameters from 6 up to as large as 68 nm. Interestingly, circular dichroism and Fourier transform infrared spectra showed that, unlike typical amyloid fibrils, which have a cross-β-sheet structure, these aggregates have a very similar secondary structure to that of the native protein, which is composed of two α-helices and eight β-strands, as determined by NMR techniques. Surface structure analysis showed that the positively charged and negatively charged residues were clustered on opposite sides, and strong electrostatic interactions between molecules were therefore very likely, which was confirmed by cross-linking experiments. In addition, several hydrophobic residues were found to constitute a continuous hydrophobic surface. These results and protein aggregation prediction using the TANGO algorithm led us to synthesize peptide Thr84 to Ser116, which, very interestingly, was found to form amyloid-like fibrils with a cross-β structure. Thus, our data suggested that human pancreatitis-associated protein fibrillization is initiated by protein aggregation primarily because of electrostatic interactions, and the loop from residues 84 to 116 may play an important role in the formation of fibrillar aggregates with a native-like conformation. [ABSTRACT FROM AUTHOR]

Studies the resonance assignments and secondary structure of murine angiogenin 4. Characteristics of the angiogenin ribonucleases; Role of the angiogenin enzymes in intestinal immunity and host defense; Use of x-ray crystallography in to study the structure of angiogenins.

By concurrently manipulating the degrees of freedom associated with polarization and orbital angular momentum (OAM), a variety of vector fields can be generated, which exhibit unique characteristics and have found extensive application in both classical and quantum optics. However, the OAM dimensions in these fields have been predominantly confined to two. Different from high-order OAM with a large topological charge, broadening the OAM dimensions beyond this limit and generating OAM spectra with multiple OAM modes can significantly enhance the scope of research. In this study, we explore vector fields with OAM dimensions exceeding ten, achieving polarization-controlled spectra in higher-dimensional OAM. Our findings not only offer a method for controlling high-dimensional OAM through polarization but also pave the way for potential applications in both classical and quantum realms utilizing high-dimensional vector states.

Presents a letter to the editor discussing resonance assignments and secondary structure of the cytotoxic RNase 3 from oocytes of bullfrog Rana catesbeiana.

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers capbinding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. [ABSTRACT FROM AUTHOR]