It remains unclear whether conservative treatment should be used to treat the common undisplaced femoral neck fractures that develop in the elderly. Herein, we systematically review the rates of ...union and avascular necrosis after conservative and surgical treatment of undisplaced femoral neck fractures.
We searched the EMBASE, PubMed, OVID, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials or observational studies that assessed the outcomes of conservative or surgical treatments of undisplaced femoral neck fractures. No language or publication year limitation was imposed. Statistical analyses were performed with the aid of the chi-squared test. We evaluated the quality of each publication and the risk of bias.
Twenty-nine studies involving 5071 patients were ultimately included; 1120 patients were treated conservatively and 3951 surgically. The union rates were 68.8% (642/933) and 92.6% (635/686) in the former and latter groups, respectively (p < 0.001). The avascular necrosis rate in the conservatively treated group was 10.3% (39/380), while it was 7.7% (159/2074) in the surgically treated group (p = 0.09).
Surgery to treat undisplaced femoral neck fractures was associated with a higher union rate and a tendency toward less avascular necrosis than conservative treatment.
The epigenetic modification 5-hydroxymethylcytosine (5hmC) plays a crucial role in the regulation of gene expression. Although some methods have been developed to detect 5hmC, direct genome-wide ...mapping of 5hmC at base resolution is still highly desirable. Herein, we proposed a single-step deamination sequencing (SSD-seq) method, designed to precisely map 5hmC across the genome at single-base resolution. SSD-seq takes advantage of a screened engineered human apolipoprotein B mRNA-editing catalytic polypeptide-like 3A (A3A) protein, known as eA3A-v10, to selectively deaminate cytosine (C) and 5-methylcytosine (5mC) but not 5hmC. During sequencing, the deaminated C and 5mC are converted to uracil (U) and thymine (T), read as T in the sequencing data. However, 5hmC remains unaffected by eA3A-v10 and is read as C during sequencing. Consequently, the presence of C in the sequence reads indicates the original 5hmC. We applied SSD-seq to generate a base-resolution map of 5hmC in human lung tissue. Our findings revealed that 5hmC was predominantly localized to CpG dinucleotides. Furthermore, the base-resolution map of 5hmC generated by SSD-seq demonstrated a strong correlation with prior ACE-seq results. The advantages of SSD-seq are its single-step process, absence of bisulfite treatment or DNA glycosylation, cost effectiveness, and ability to detect and quantify 5hmC directly at single-base resolution.
Hypoxia/oxygen-sensing signally is closely associated with many tumor progressions, including osteosarcoma (OS). Previous research principally focused on the function of hypoxia-inducible factor ...(HIF)-1α and HIF-2α as the major hypoxia-associated transcription factors in OS, however, the role of HIF-3α has not been investigated. Our study found that HIF-3α was upregulated in OS tissues and cell lines. HIF-3α overexpression facilitated cell proliferation and invasion, and inhibited apoptosis, whereas HIF-3α knockdown showed the opposite results. Chromatin immunoprecipitation analysis revealed that lysine demethylase 3A (KDM3A) expression was transcriptionally activated by HIF-3α under hypoxia, and KDM3A occupied the SRY-box transcription factor 9 (SOX9) gene promoter region through H3 lysine 9 dimethylation (H3K9me2). Additionally, rescue results revealed that KDM3A or SOX9 overexpression reversed the effects of HIF-3α silence on cell functions. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway inhibitor cucurbitacin I suppressed the promotive effects of HIF-3α overexpression on cell proliferation, invasion and TAK2/STAT3 pathway. Finally, OS cell line MG-63 transfected with HIF-3α short hairpin RNA (HIF-3α shRNA) were subcutaneously injected into nude mice, and the results found that HIF-3α knockdown significantly inhibited the xenograft tumor growth of OS in vivo. In conclusion, this study reveals that HIF-3α promotes OS progression in vitro and in vivo by activating KDM3A-mediated SOX9 promoter demethylation, which may provide a potential therapeutic mechanism for OS.
•HIF-3α expression is upregulated in OS tissues and cell lines.•HIF-3α overexpression facilitated OS cell proliferation and invasion.•HIF-3α promotes OS progression by KDM3A-mediated SOX9 promoter demethylation.•HIF-3α promotes OS progression through activating the JAK2/STAT3 pathway.•HIF-3α interference impeded xenograft tumor development in mice.
Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial ...players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca
2+
(Ca
2+
i
) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of Ca
2+
i
in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca
2+
/YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy.
Cytosine modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), play crucial roles in numerous biological processes. Current analytical methods are often constrained ...to the separate detection of either 5mC or 5hmC, or the combination of both modifications. The ability to simultaneously detect C, 5mC, and 5hmC at the same genomic locations with precise stoichiometry is highly desirable. Herein, we introduce a method termed engineered deaminase-assisted sequencing (EDA-seq) for the simultaneous quantification of C, 5mC, and 5hmC at the same genomic sites. EDA-seq utilizes a specially engineered protein, derived from human APOBEC3A (A3A), known as eA3A-M5. eA3A-M5 exhibits distinct deamination capabilities for C, 5mC, and 5hmC. In EDA-seq, C undergoes complete deamination and is sequenced as T. 5mC is partially deaminated resulting in a mixed readout of T and C, and 5hmC remains undeaminated and is read as C. Consequently, the proportion of T readouts (
P
T
) reflects the collective occurrences of C and 5mC, regulated by the deamination rate of 5mC (
R
5mC
). By determining
R
5mC
and
P
T
values, we can deduce the precise levels of C, 5mC, and 5hmC at particular genomic locations. We successfully used EDA-seq to simultaneously measure C, 5mC, and 5hmC at specific loci within human lung cancer tissue and their normal counterpart. The results from EDA-seq demonstrated a strong concordance with those obtained from the combined application of BS-seq and ACE-seq methods. EDA-seq eliminates the need for bisulfite treatment, DNA oxidation or glycosylation and uniquely enables simultaneous quantification of C, 5mC and 5hmC at the same genomic locations.
We developed the EDA-seq method, which enables the simultaneous and quantitative detection of C, 5mC, and 5hmC in DNA at single-base resolution.
When the Laguerre-based finite-difference time-domain (FDTD) method is used for electromagnetic problems, a huge sparse matrix equation results, which is very expensive to solve. We previously ...introduced an efficient algorithm for implementing an unconditionally stable 2-D Laguerre-based FDTD method. We numerically verified that the efficient algorithm can save CPU time and memory storage greatly while maintaining comparable computational accuracy. This paper presents new efficient algorithm for implementing unconditionally stable 3-D Laguerre-based FDTD method. To do so, a factorization-splitting scheme using two sub-steps is adopted to solve the produced huge sparse matrix equation. For a full update cycle, the presented scheme solves six tri-diagonal matrices for the electric field components and computes three explicit equations for the magnetic field components. A perfectly matched layer absorbing boundary condition is also extended to this approach. In order to demonstrate the accuracy and efficiency of the proposed method, numerical examples are given.
There are still many challenges to acquire the optimal integration of biomedical materials with the surrounding tissues. Gene coatings on the surface of biomaterials may offer an effective approach ...to solve the problem. In order to investigate the gene multilayers mediated differentiation of mesenchymal stem cells (MSCs), gene functionalized films of hyaluronic acid (HA) and lipid-DNA complex (LDc) encoding cartilage oligomeric matrix protein (COMP) were constructed in this study via the layer-by-layer self-assembly technique. Characterizations of the HA/DNA multilayered films indicated the successful build-up process. Cells could be directly transfected by gene films and a higher expression could be obtained with the increasing bilayer number. The multilayered films were stable for a long period and DNA could be easily released in an enzymatic condition. Real-time polymerase chain reaction (RT-PCR) assay presented significantly higher (p<0.01) COMP expression of MSCs cultured with HA/COMP multilayered films. Compared with control groups, the osteogenic gene expression levels of MSCs with HA/COMP multilayered films were down-regulated while the chondrogenic gene expression levels were up-regulated. Similarly, the alkaline phosphatase (ALP) staining and Alizarin red S staining of MSCs with HA/COMP films were weakened while the alcian blue staining was enhanced. These results demonstrated that HA/COMP multilayered films could inhibit osteogenic differentiation and promote chondrogenic differentiation of MSCs, which might provide new insight for physiological ligament-bone healing.
A new two-dimensional (2-D) finite-difference time domain (FDTD) method applied to scattering by infinite objects with oblique incidence is proposed. 2-D Maxwell's equations, differential equations, ...and perfectly matched layer (PML) absorbing boundary conditions (ABC) are derived. The incident wave, computed by the 1-D FDTD method, is set on the connecting boundary. The accuracy and the efficiency of the proposed method have been verified by comparing the results of the split-field periodic FDTD method, the sine-cosine method, and the transmission line theory method with the proposed method.
This study explored the function of circular RNA VMA21 (circVMA21) in osteoarthritis (OA). IL-1β inducement reduced the expression of circVMA21 in C28/I2 cells and human primary chondrocytes. Forced ...expression of circVMA21 heightened cell viability and attenuated cell apoptosis, accompanied by upregulation of Bcl-2, and downregulation of Bax and C-caspase-3 in C28/I2 cells in response to IL-1β exposure. CircVMA21 overexpression diminished the expression of MMP1 and MMP13, augmented the expression of COL2A1, and impeded the production of IL-6, TNF-α, prostaglandin E2 (PGE2) and NO. CircVMA21 served as a competitive endogenous RNA by sponging miR-495-3p. F-box and WD40 domain protein 7 (FBWX7) was identified as a target of miR-495-3p. The compensation experiments affirmed that circVMA21-mediated protective effects on IL-1β-irritated chondrocytes through the miR-495-3p/FBWX7 axis. The role of circVMA21 was also confirmed in an OA rat model. Collectively, these findings revealed a protective effect of circVMA21in OA by intercepting the miR-495-3p/FBWX7 crosstalk.
•CircVMA21 was diminished in human chondrocytes challenged by IL-1β.•CircVMA21 protected chondrocytes against IL-1β-triggered apoptosis, inflammatory insult and cartilage degradation.•CircVMA21 functioned as a ceRNA by efficaciously sponging miR-495-3p thereby adjusting FBWX7 expression.•The miR-495-3p/FBWX7 axis participated in the protective roles of circVMA21 in IL-1β-engendered chondrocyte damage.
Hydrophobic nano silver films were fabricated on butterfly wings as bio-template. The micrometric/nano structures and hydrophobicity of the surfaces were investigated with the help of scanning ...electron microscope（SEM） and video-based contact angle meter. The hydrophobic mechanism of silver film was analyzed with the aid of Cas- sie＇s formula. On the nano silver films of various thicknesses（5, 10, 20, 40, 60, 80, 100 nm）, all the contact an- gles（CAs） of water were bigger than 120°. When the silver film was 5 nm, the CAs of water on it on the wing surfa- ces of Mimathyma nycteis and Speyeria aglaja were 143.2° and 139.2°, respectively. Coated with the sliver film of the same thickness, butterfly wing surface exhibited the CA remarkably bigger than glass slide surface, exhibiting its high hydrophobicity. With the increase of silver film thickness on butterfly wing surface, the hydrophobicity kept de- creasing. The micrometric/nano hierarchical structures on butterfly wing surface result in the transition of metal silver from hydrophilicity to hydrophobicity.
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