Development of an in situ polymeric hydrogel implant of methylprednisolone for spinal injuries

Purpose: To prepare and characterize in situ gel-forming implants of methylprednisolone for the treatment of spinal cord injuries.Methods: In situ hydrogels of methylprednisolone were prepared by dispersing polylactide glycolic acid (PLGA) polymer and methylprednisolone in N-methyl-pyrrolidone solvent, and subsequent membrane sterilization. Hydrogels were prepared using varying concentrations of PLGA polymer. The physicochemical properties of hydrogels, including visual appearance, clarity, pH, viscosity, drug content, and in vitro drug release, were characterized. In vivo studies were performed to examine antiinflammatory activity (paw edema test) and in vivo motor function activity in a rat spinal injury model after injecting the hydrogels into rats.Results: The physicochemical properties of the gels were satisfactory. F1, F2, F3, and F4 formulations showed 99.67, 95.29, 88.89 and 88.20 % drug release, respectively, at the end of 7 days. In vivo antiinflammatory activity was highest for F1 (62.85 %). Motor function activity scores (arbitrary scale) for the F1, F2, F3 and F4 formulations were 4.82 ± 0.12, 4.70 ± 0.12, 4.68 ± 0.02, and 4.60 ± 0.05, respectively, and were higher (p < 0.05) for F1, F2 and F3) than for the standard (methylprednisolone, 30 mg/kg body weight, iv; activity score, 4.59 ± 0.20).Conclusions: The in situ hydrogels of methylprednisolone developed may be useful for the effective management of spinal cord injuries in patients. However, further investigations are required to ascertain their suitability for clinical use.Keywords: Methylprednisolone, In situ hydrogel, Spinal injury, Motor activity, Implan

A high-precision result for a full-color three-loop three-point form factor in N=4{\cal N}=4 SYM

We perform a high-precision computation of the three-loop three-point form factor of the stress-tensor supermultiplet in ${\cal N}=4$ SYM. Both the leading-color and non-leading-color form factors are expanded in terms of simple integrals. We compute the complete set of integrals at a special kinematic point with very high precision using $\mathtt{AMFlow}$. The high-precision leading-color result enables us to obtain the analytic form of a numerical constant in the three-loop BDS ansatz, which is previously known only numerically. The high-precision values of the non-leading-color finite remainder as well as all integrals are also presented, which can be valuable for future use.Comment: 6 pages, 25 pages of appendi

Heavy-quark pair production at lepton colliders at NNNLO in QCD

We compute the total cross-section and invariant mass distribution for heavy-quark pair production in $e^+e^-$ annihilation at the next-to-next-to-next-to-leading order in QCD. The obtained results are expressed as piecewise functions defined by several deeply expanded power series, facilitating a rapid numerical evaluation. Utilizing top-pair production at a collision energy of 500 GeV as a benchmark, we observe a correction of approximately $0.1\%$ for the total cross-section and around $10\%$ for the majority of the invariant mass distribution range. These results play a crucial role in significantly reducing theoretical uncertainty: the scale dependence has been diminished to $0.06\%$ for the total cross-section and to $5\%$ for the invariant mass distribution. This reduction of uncertainty meets the stringent requirements of future lepton colliders.Comment: 7 pages, 5 figures; invariant mass distribution for heavy-quark pair added; version published at PR

Characterization and Localization of Cyclin B3 Transcript in Both Oocyte and Spermatocyte of the Rainbow Trout (Oncorhynchus Mykiss)

B-type cyclins are regulatory subunits with distinct roles in the cell cycle. To date, at least three subtypes of B-type cyclins (B1, B2, and B3) have been identified in vertebrates. Previously, we reported the characterization and expression profiles of cyclin B1 and B2 during gametogenesis in the rainbow trout (Oncorhynchus mykiss). In this paper, we isolated another subtype of cyclin B, cyclin B3 (CB3), from a cDNA library of the rainbow trout oocyte. The full-length CB3 cDNA (2,093 bp) has an open reading frame (1,248 bp) that encodes a protein of 416 amino acid residues. The CB3 transcript was widely distributed in all the examined tissues, namely, eye, gill, spleen, brain, heart, kidney, stomach, skin, muscle, and, especially, gonad. Northern blot analysis indicated only one form of the CB3 transcript in the testis and ovary. In situ hybridization revealed that, in contrast to cyclin B1 and B2 transcripts, CB3 transcripts were localized in the oocytes, spermatocytes, and spermatogonia. These findings strongly suggest that CB3 plays a role not only as a mitotic cyclin in spermatogonial proliferation during early spermatogenesis but also during meiotic maturation of the spermatocyte and oocyte in the rainbow trout

Complete two-loop electroweak corrections to e+e−→HZe^+e^-\rightarrow HZ

We compute the complete two-loop electroweak corrections to the Higgsstralung process $e^+e^-\rightarrow HZ$ at the future Higgs factory. The Feynman integrals involved in the computation are decomposed into linear combinations of a minimal set of master integrals taking advantage of the recent developments of integral reduction techniques. The master integrals are then evaluated by differential equations with boundary conditions provided by the auxiliary mass flow method. Our final result for given $\sqrt{s}$ is expressed as a piecewise function defined by several deeply expanded power series, which has high precision and can be further manipulated efficiently. Our calculation presents the first complete two-loop electroweak corrections for processes with four external particles.Comment: 5 pages, 2 figures. arXiv admin note: text overlap with arXiv:2209.1425

Activation of transient receptor potential vanilloid 1 protects the heart against apoptosis in ischemia/reperfusion injury through upregulating the PI3K/Akt signaling pathway

Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel and a molecular integrator of noxious stimuli. TRPV1 activation confers cardiac protection against ischemia/reperfusion (I/R) injury. The present study aimed to investigate whether the cardioprotective effects of TRPV1 were associated with the inhibition of apoptosis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathways. Briefly, the hearts of TRPV1 knockout (TRPV1-/-) or wild-type (WT) mice were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion in a Langendorff apparatus in the presence or absence of the PI3K inhibitor, LY294002. At the end of reperfusion, infarct size was measured using 2, 3, 5-triphenyltetrazolium chloride staining and myocardial apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and phosphorylated Akt and ERK1/2 were determined by western blot analysis. There was a significant increase in the extent of infarction and the percentage of TUNEL-positive cells, and a decrease in the Bcl-2/Bax ratio, and Akt and ERK1/2 phosphorylation in TRPV1-/- hearts. In addition, treatment with LY294002 increased infarct size and the percentage of TUNEL-positive cells, and reduced Bcl-2/Bax expression and Akt phosphorylation in WT hearts, but not in TRPV1-/- hearts, following I/R. Taken together, these data suggested that TRPV1 serves a protective role against myocardial apoptosis during I/R via the PI3K/Akt signaling pathway. In conclusion, activating TRPV1 may be considered a potential approach to protect the heart against I/R injury

Effects of triazolodiazepine on the production of interleukin-6 from murine spleen cells and rabbit synovial cells in vitro

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase anaphylactic reaction, and haematopoiesis. Lipopolysaccharide (6–24 μg/ml) significantly induced IL-6 release from murine spleen cells. In cultured rabbit synovial cells interleukin-1 (IL-1, 1–10 U/ml) induced IL-6 production in a concentration-dependent manner. Triazolodiazepine (Tri) is a hetrazepine platelet-activating factor antagonist. In this study we found that Tri (0.1–10 μmol/l) exerted strong inhibitory effects on LPS stimulated IL-6 production in murine spleen cells. Kinetic studies showed that the inhibition of IL-6 release was time-independent. In rabbit synovial cells Tri also reduced IL-6 release induced by IL-1 and tumour necrosis factor. Inhibition of cytokine production by Tri may partially explain its wide and strong anti-inflammatory effects

Long-term nitrogen fertilization decreased the abundance of inorganic phosphate solubilizing bacteria in an alkaline soil

Inorganic phosphate solubilizing bacteria (iPSB) are essential to facilitate phosphorus (P) mobilization in alkaline soil, however, the phylogenetic structure of iPSB communities remains poorly characterized. Thus, we use a reference iPSB database to analyze the distribution of iPSB communities based on 16S rRNA gene illumina sequencing. Additionally, a noval pqqC primer was developed to quantify iPSB abundance. In our study, an alkaline soil with 27-year fertilization treatment was selected. The percentage of iPSB was 1.10 similar to 2.87% per sample, and the dominant iPSB genera were closely related to Arthrobacter, Bacillus, Brevibacterium and Streptomyces. Long-term P fertilization had no significant effect on the abundance of iPSB communities. Rather than P and potassium (K) additions, long-term nitrogen (N) fertilization decreased the iPSB abundance, which was validated by reduced relative abundance of pqqC gene (pqqC/16S). The decreased iPSB abundance was strongly related to pH decline and total N increase, revealing that the long-term N additions may cause pH decline and subsequent P releases relatively decreasing the demands of the iPSB community. The methodology and understanding obtained here provides insights into the ecology of inorganic P solubilizers and how to manipulate for better P use efficiency