Age-Related Changes of the Zygomatic Ligament: An Experimental Animal Study.

BACKGROUND: Facial aging is a multifactorial process involving the skin, fat, muscles, bones, and ligaments. The role of facial ligaments in the facial aging process remains elusive. OBJECTIVES: The aim of this study was to identify whether age-related changes in facial ligaments exist and how to best quantify such changes when investigating the zygomatic ligament in the rat. METHODS: A total of 30 male Sprague-Dawley rats (10 young, 10 middle-aged, 10 mature) were investigated to visualize the zygomatic ligament. Samples of the ligaments spanning the zygomatic arch and the skin were taken and histologically examined with hematoxylin-eosin, Masson, Verhoeff's elastic, and picrosirius red staining. Quantification of the Type I/III collagen ratio and collagen content was performed by color deconvolution and electron microscopic imaging. RESULTS: With increasing age, collagen fibers inside of the examined ligaments appeared thicker and more closely arranged. The Type I/III collagen ratio was measured to be 1.74 in young animals, 3.93 in middle-aged animals, and 5.58 in mature animals. The ultra-microstructure of the ligament was less coordinated in direction and orientation in young and middle-aged animals than in mature animals, in which collagen fibers were bundled together in a strong and oriented mesh. CONCLUSIONS: Ligaments appeared thinner, transparent, more elastic, and less robust in young animals, whereas ligaments in mature animals appeared thicker, more fascia-like, less elastic, and more robust. An increase in the Type I/III collagen ratio, indicating greater stiffness and reduced elasticity, was observed with higher age of the investigated animals. These findings indicate that ligaments might increase in stiffness and rigidity with age.

Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis. In contrast, overexpression of Sirt3 enhanced deacetylation of COX-1 and inhibited oxidative stress-induced apoptotic cell death. Significantly, rats treated with ischemia/reperfusion injury, a typical oxidative stress-related disease, presented an inhibition of Sirt3-induced hyperacetylation of COX-1 in the brain tissues. Furthermore, K13, K264, K319, and K481 were identified as the acetylation sits of COX-1 in response to oxidative stress. In conclusion, COX-1 was discovered as a new deacetylation target of Sirt3, indicating that the Sirt3/COX-1 axis is a promising therapy target of stress-related diseases.-Tu, L.-F., Cao, L.-F., Zhang, Y.-H., Guo, Y.-L., Zhou, Y.-F., Lu, W.-Q., Zhang, T.-Z., Zhang, T., Zhang, G.-X., Kurihara, H., Li, Y.-F., He, R.-R. Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

Upgrade of laser pump time-resolved X-ray probes in Beijing synchrotron.

The upgrade of the laser pump time-resolved X-ray probes, namely time-resolved X-ray absorption spectroscopy (TR-XAS) and X-ray diffraction (TR-XRD), implemented at the Beijing Synchrotron Radiation Facility, is described. The improvements include a superbunch fill, a high-efficiency fluorescence collection, an efficient spatial overlap protocol and a new data-acquisition scheme. After upgrade, the adequate TR-XAS signal is now obtained in a 0.3 mM solution, compared with a 6 mM solution in our previous report. Furthermore, to extend application in photophysics, the TR-XAS probe is applied on SrCoO2.5 thin film. And for the first time, TR-XAS is combined with TR-XRD to simultaneously detect the kinetic trace of structural changes in thin film.

Implementation of ultrafast X-ray diffraction at the 1W2B wiggler beamline of Beijing Synchrotron Radiation Facility.

The implementation of a laser pump/X-ray probe scheme for performing picosecond-resolution X-ray diffraction at the 1W2B wiggler beamline at Beijing Synchrotron Radiation Facility is reported. With the hybrid fill pattern in top-up mode, a pixel array X-ray detector was optimized to gate out the signal from the singlet bunch with interval 85 ns from the bunch train. The singlet pulse intensity is ∼2.5 × 10(6) photons pulse(-1) at 10 keV. The laser pulse is synchronized to this singlet bunch at a 1 kHz repetition rate. A polycapillary X-ray lens was used for secondary focusing to obtain a 72 µm (FWHM) X-ray spot. Transient photo-induced strain in BiFeO3 film was observed at a ∼150 ps time resolution for demonstration.

Functional analysis of nuclear receptor genes in molting and metamorphosis of the cigarette beetle, Lasioderma serricorne.

Nuclear receptors (NRs) are ligand-regulated transcription factors that are important for the normal growth and development of insects. However, systematic function analysis of NRs in the molting process of Lasioderma serricorne has not been reported. In this study, we identified and characterized 16 NR genes from L. serricorne. Spatiotemporal expression analysis revealed that six NRs were mainly expressed in 3-d-old 4th-instar larvae; five NRs were primarily expressed in 5-d-old adults and four NRs were predominately expressed in prepupae. All the NRs were highly expressed in epidermis, fat body and foregut. RNA interference (RNAi) experiments revealed that knockdown of 15 NRs disrupted the larva-pupa-adult transitions and caused 64.44-100 % mortality. Hematoxylin-eosin staining showed that depletion of 12 NRs prevented the formation of new cuticle and disrupted apolysis of old cuticle. Silencing of LsHR96, LsSVP and LsE78 led to newly formed cuticle that was thinner than the controls. The 20E titer and chitin content significantly decreased by 17.67-95.12 % after 15 NR dsRNA injection and the gene expression levels of 20E synthesis genes and chitin metabolism genes were significantly reduced. These results demonstrated that 15 NR genes are essential for normal molting and metamorphosis of L. serricorne by regulating 20E synthesis and chitin metabolism.

Late­onset white cord syndrome following anterior cervical discectomy and fusion: A case report.

White cord syndrome refers to an emerging neurological dysfunction occurring after spinal decompression surgery with hyperenhancing changes on T2-weighted magnetic resonance imaging (T2WI). The pathophysiological mechanism is hypothesized to be an ischemia-reperfusion injury following chronic ischemic spinal cord decompression. A 54-year-old man was admitted to Jinhua Municipal Central Hospital with complaints of numbness and weakness in the extremities and swelling in the neck. MRI showed degeneration and herniation of the C4-C7 intervertebral discs. The patient underwent anterior cervical corpectomy and fusion (ACCF). On the 7th postoperative day, the patient reappeared with weakness of the limbs. Physical examination revealed paralysis. Emergency MRI suggested T2 high signal myelopathy and emergency surgery was performed following the diagnosis of white cord syndrome. Following the operation, the patient's neurological system gradually improved. The motor ability and sensory function of the extremities recovered at 7-month follow-up. Spine surgeons should be aware of this serious complication. The present case serves to provide experience for clinical treatment and diagnosis and encourage research into its pathophysiology.

Biofilm formation is a risk factor for late and delayed complications of filler injection.

Introduction: Biofilm formation is a major cause of delayed-graft complications. Similarly to implants, dermal fillers carry the risk of biofilm formation, which can lead to the development of nodules, chronic inflammatory reactions, abscesses and other complications. In this study, we investigated the late or delayed complications associated with biofilm formation on dermal fillers. Methods: In this retrospective analysis, we analyzed all cases of complications caused by filler injections at a single center between January 2017 and December 2022, the majority of which comprised nodule formation and chronic persistent inflammatory reactions. The risk of biofilm formation with fillers was summarized and analyzed based on the results of bacterial culture and pathological examination. Results: Sixty-one patients were enrolled, including 42 cases of nodule formation, 15 of chronic inflammatory reactions, and 4 of active infection. Bacterial culture of the tissue samples obtained from seven patients after surgical treatment were positive, and comprised four cases of Staphylococcus aureus, one case of Staphylococcus epidermidis, one case of Staphylococcus saprophyticus and one case of Mycobacterium abscessus. The corresponding histopathological results indicated extensive mononuclear lymphocyte infiltration, with a giant cell reaction in the fibrous connective tissue. Conclusion: The results of this study suggest that biofilm formation is a significant risk factor for late and delayed complications following filler injection, and is caused by the contamination of resident bacteria and recessive infection at the injection site.

GPX4 deficiency-dependent phospholipid peroxidation drives motor deficits of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by oxidative stress that triggers motor neurons loss in the brain and spinal cord. However, the mechanisms underlying the exact role of oxidative stress in ALS-associated neural degeneration are not definitively established. Oxidative stress-generated phospholipid peroxides are known to have extensive physiological and pathological consequences to tissues. Here, we discovered that the deficiency of glutathione peroxidase 4 (GPX4), an essential antioxidant peroxidase, led to the accumulation of phospholipid peroxides and resulted in a loss of motor neurons in spinal cords of ALS mice. Mutant human SOD1G93A transgenic mice were intrathecally injected with neuron-targeted adeno-associated virus (AAV) expressing GPX4 (GPX4-AAV) or phospholipid peroxidation inhibitor, ferrostatin-1. The results showed that impaired motor performance and neural loss induced by SOD1G93A toxicity in the lumbar spine were substantially alleviated by ferrostatin-1 treatment and AAV-mediated GPX4 delivery. In addition, the denervation of neuron-muscle junction and spinal atrophy in ALS mice were rescued by neural GPX4 overexpression, suggesting that GPX4 is essential for the motor neural maintenance and function. In comparison, conditional knockdown of Gpx4 in the spinal cords of Gpx4fl/fl mice triggered an obvious increase of phospholipid peroxides and the occurrence of ALS-like motor phenotype. Altogether, our findings underscore the importance of GPX4 in maintaining phospholipid redox homeostasis in the spinal cord and presents GPX4 as an attractive therapeutic target for ALS treatment.

Mannose inhibits proliferation and promotes apoptosis to enhance sensitivity of glioma cells to temozolomide through Wnt/ß-catenin signaling pathway.

BACKGROUND: Temozolomide (TMZ) is generally applied for glioma treatment, while drug resistance of TMZ limits its therapeutic efficacy. Mannose exerts evident anti-tumor effect. We intended to investigate whether mannose enhanced TMZ sensitivity to glioma and examined the underlying mechanism. METHODS: MTT and clone formation assays were performed to detect cell viability and proliferation. Cell apoptosis was measured by flow cytometry. The protein and gene expression levels were detected by Western blot and qRT-PCR assays. Xenograft glioma model was established to explore the influence of mannose in vivo. RESULTS: Mannose inhibited glioma cell growth, which was facilitated by knockdown of phosphomannose isomerase (PMI) while reversed by overexpression of PMI. Mannose enhanced the sensitivity of glioma cells to TMZ, indicated by the further inhibited cell viability and colony formation and the aggravated cell apoptosis, which was reversed by overexpression of O6-methylguanine DNA methyltransferase (MGMT). Furthermore, mannose and TMZ inhibited MGMT expression and Wnt/ß-catenin activation. Moreover, activating Wnt/ß-catenin pathway blocked anti-proliferative effect induced by mannose and TMZ, which was further suppressed by overexpressed MGMT. Mannose inhibited glioma growth, suppressed Ki67 and downregulated MGMT and ß-catenin in vivo. CONCLUSION: Mannose inhibited MGMT to enhance sensitivity of glioma cells to TMZ, with Wnt/ß-catenin pathway involvement. Our data suggested that mannose could be an innovative agent to improve glioma treatment, particularly in TMZ-resistant glioma with high MGMT.

Ruthenium(II) mixed-ligand complex containing 2-(4'-benzyloxy-phenyl)imidazo[4,5-f][1,10]phenanthroline: synthesis, DNA-binding and photocleavage studies.

A novel polypyridyl ligand 2-(4'-benzyloxyphenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and its complex [Ru(bpy)2(BPIP)]2+ (1) (bpy=2,2'-bipyridine) and (2) [Ru(phen)2(BPIP)]2+) (phen=1,10-phenanthroline) have been synthesized and characterized by elemental analysis, electrospray mass spectra and 1H NMR. The DNA-binding properties of the two complexes were investigated by spectroscopic and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode. Both complexes can enantioselectively interact with calf thymus DNA (CT-DNA) in a way. The Lambda enantiomer of complex 1 is slightly predominant for binding to CT-DNA to the Delta enantiomer. Under irradiation at 365 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA. Inhibitors studies suggest that singlet oxygen ((1)O2) and hydroxyl radical (*OH) play a significant role in the cleavage mechanism for both complexes. Moreover, the DNA-binding and photocleavage properties of both complexes were compared with that of [Ru(bpy)2(BPIP)]2+ and [Ru(phen)2(BPIP)]2+. The experimental results indicate that methene group existence or not have a significant effect on the DNA-binding and cleavage mechanism of these complexes.