Suppression of Overactive Insulin-Like Growth Factor 1 Attenuates Trauma-Induced Heterotopic Ossification in Mice.

Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) was demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. The current study used an Achilles tendon puncture-induced HO model to show that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. Micro-computed tomography imaging showed that IGF-1 not only accelerated the rate of osteogenesis and increased ectopic bone volume but also induced spontaneous ectopic bone formation in undamaged Achilles tendons. Blocking IGF-1 activity with IGF-1 antibody or IGF-1 receptor inhibitor picropodophyllin significantly inhibited HO formation. Mechanistically, IGF-1/IGF-1 receptor activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling to promote the phosphorylation of mTOR, resulting in the chondrogenic and osteogenic differentiation of tendon-derived stem cells into chondrocytes and osteoblasts in vitro and in vivo. Inhibitors of PI3K (LY294002) and mTOR (rapamycin) both suppressed the IGF-1-stimulated mTOR signal and mitigated the formation of ectopic bones significantly. In conclusion, these results indicate that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.

MAPRE3 as an epigenetic target of EZH2 restricts ovarian cancer proliferation in vitro and in vivo.

Ovarian cancer (OC) is a lethal gynecologic cancer and the common cause of death within women worldwide. The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase highly expressed in various tumors, including OC. However, the mechanistic basis of EZH2 oncogenic activity in OC remain incompletely understood. Bioinformatics analysis showed that the expression of MAPRE3 was lower in OC tissues than in normal tissues, and was positively correlated with the overall survival. MAPRE3 overexpression decreased cell growth, inducing cell cycle arrest and apoptosis in OC cells, whereas MAPRE3 silencing promoted proliferation and accelerated cell cycle progression of OC cells. The in vivo study validated that overexpression of MAPRE3 impeded tumor formation and growth of OC xenografts in nude mice. In addition, knockdown of EZH2 in OC cells downregulated H3K27me3 expression and increased MAPRE3 expression. Inhibiting EZH2 in OC cells reduced the enrichment of H3K27me3 on the promoter of MAPRE3. Furthermore, MAPRE3 silencing significantly reversed changes in the expression of cell cycle and apoptosis-related markers and cell growth mediated by EZH2 knockdown in OC cells. MAPRE3 functions as a suppressor of OC and is epigenetic repressed by EZH2, suggesting a potential therapeutic strategy for OC by targeting EZH2/MAPRE3 axis.

Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

Linear-coupling-induced double-period pulsating vector solitons in lasers.

Pulsating solitons is a universal phenomenon originating from the Hopf-type bifurcation in dissipative systems such as lasers and microresonators. Here, we report the vector soliton in a fiber laser pulsating with two periods of different orders of magnitude. The short-period pulsation manifests as the period-tripling facilitated by the linear coupling between orthogonal polarization components, which breaks the self-consistent evolution of the vector soliton over a single round trip (RT). The long-period pulsation arises from the mode competition between the two polarization components mediated by various cavity effects. The interplay between linear coupling and mode competition gives rise to the robust double-period pulsating (DPP) vector soliton. Our results provide a clear physical mechanism for the broadly observed double-period breather, which has a significant value in exploring breathers with complex dynamics and multiple comb spectroscopy.

Transcriptome analysis of Kluyveromyces marxianus under succinic acid stress and development of robust strains.

Kluyveromyces marxianus has become an attractive non-conventional yeast cell factory due to its advantageous properties such as high thermal tolerance and rapid growth. Succinic acid (SA) is an important platform molecule that has been applied in various industries such as food, material, cosmetics, and pharmaceuticals. SA bioproduction may be compromised by its toxicity. Besides, metabolite-responsive promoters are known to be important for dynamic control of gene transcription. Therefore, studies on global gene transcription under various SA concentrations are of great importance. Here, comparative transcriptome changes of K. marxianus exposed to various concentrations of SA were analyzed. Enrichment and analysis of gene clusters revealed repression of the tricarboxylic acid cycle and glyoxylate cycle, also activation of the glycolysis pathway and genes related to ergosterol synthesis. Based on the analyses, potential SA-responsive promoters were investigated, among which the promoter strength of IMTCP2 and KLMA_50231 increased 43.4% and 154.7% in response to 15 g/L SA. In addition, overexpression of the transcription factors Gcr1, Upc2, and Ndt80 significantly increased growth under SA stress. Our results benefit understanding SA toxicity mechanisms and the development of robust yeast for organic acid production. KEY POINTS: • Global gene transcription of K. marxianus is changed by succinic acid (SA) • Promoter activities of IMTCP2 and KLMA_50123 are regulated by SA • Overexpression of Gcr1, Upc2, and Ndt80 enhanced SA tolerance.

Linear coupling-related pulse splitting in fiber lasers.

We demonstrate a unique pulse-splitting mechanism dominated by the linear coupling between two vector modes in a mode-locked fiber laser using polarization-maintaining fiber. As the linear coupling strength increases, the pulse experiences larger perturbations and manifests as stronger spectral sidebands. Correspondingly, the temporal pedestals possessing a higher intensity become untrapped and eventually evolve into a stable pulse. Such linear coupling-related pulse splitting is ubiquitous both in normal- and anomalous-dispersion regimes, fundamentally differing from that induced by the excessive nonlinear phase shift. Experimental observations fully sustain numerical results and provide a flexible approach to managing the number and energy of vector solitons.

HDAC2 exacerbates rheumatoid arthritis progression via the IL-17-CCL7 signaling pathway.

Histone deacetylases (HDACs) have been reported to regulate the immune response in rheumatoid arthritis (RA). The current study aimed to explore key HDACs and their molecular mechanism in RA. First, the expression of HDAC1, HDAC2, HDAC3 and HDAC8 in RA synovial tissue was determined by qRT-PCR. The effects of HDAC2 on the proliferation, migration, invasion, and apoptosis of fibroblast-like synoviocytes (FLS) in vitro were studied. Furthermore, collagen-induced arthritis (CIA) rat models were established to evaluate the severity of arthritis in joints, and the levels of inflammatory factors were examined by immunohistochemistry staining, ELISA, and qRT-PCR. Transcriptome sequencing was used to screen differentially expressed genes (DEGs) with HDAC2 silencing in the synovial tissue of CIA rat, and downstream signaling pathways were predicted by enrichment analysis. The results showed that HDAC2 was highly expressed in the synovial tissue of RA patients and CIA rats. Overexpressed HDAC2 promoted FLS proliferation, migration, and invasion and inhibited FLS apoptosis in vitro, resulting in secretion of inflammatory factors and RA exacerbation in vivo. There were 176 DEGs, including 57 downregulated and 119 upregulated genes, after silencing HDAC2 in CIA rats. DEGs were primarily enriched in Platinum drug resistance, IL-17 as well as the PI3K-Akt signaling pathways. CCL7, which was implicated in the IL-17 signaling pathway, was downregulated after HDAC2 silencing. Furthermore, CCL7 overexpression aggravated the development of RA, which was demonstrated to be effectively attenuated by HDAC2 suppression. In conclusion, this study demonstrated that HDAC2 exacerbated the progression of RA by regulating the IL-17-CCL7 signaling pathway, suggesting that HDAC2 may be a promising therapeutic target for RA treatment.

Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

Objective: To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. Methods: A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. Results: The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Conclusions: Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

Anomalous soliton trapping in net-normal dispersion lasers.

In a nonlinear optical system with birefringence such as fiber lasers, soliton trapping can be achieved when the fast (slow) component experiences blueshift (redshift) at normal dispersion to compensate for polarization-mode dispersion (PMD). In this Letter, we demonstrate an anomalous vector soliton (VS) whose fast (slow) component shifts to the red (blue) sides, which is opposite to traditional soliton trapping. It is found that the repulsion between the two components is induced by net-normal dispersion and PMD, while the attraction is ascribed to linear mode coupling and saturable absorption. The equilibrium of attraction and repulsion permits the self-consistent evolution of VSs circulating in the cavity. Our results indicate that the stability and dynamics of VSs are worth revisiting and studying in-depth, especially in lasers with complex configurations, despite it being a well-known object in nonlinear optics.

Self-consistent soliton evolution in single-two-mode fiber lasers.

Ultrafast few-mode fiber lasers have received increasing attention from basic research to practical applications due to their unique pulse performance and intriguing nonlinear dynamics. Here, we experimentally and numerically reveal the formation and evolution behaviors of a soliton in a mode-locked fiber laser composed of two-mode and single-mode fibers. The LP11 pulse walks away from the LP01 pulse in the two-mode fiber due to modal dispersion and then transforms into an auxiliary LP01 pulse after entering the single-mode fiber. After re-entering the two-mode fiber, the LP01 pulse excites the LP11 pulse via mode coupling; therefore, the LP11 pulse also consists of dominant and auxiliary pulses. Such a soliton fiber laser converges to an asymptotic steady state with unlocked spatial modes arising from the interplay between the strong modal dispersion and weak mode coupling.

Internal dynamics in bound states of unequal solitons.

The bound states (BSs) of solitons are found to have intriguing internal dynamics in ultrafast lasers. Here, we explore the binding mechanism and internal motions of asymmetric bound state (ABS) solitons constituted by unequal solitons at short-range with their tails directly overlapped. Experiments and simulations show that the periodic energy flux between two solitons, mediated by their overlapped tails, gives rise to a balanced separation and energy distribution across the ABS. The motion mechanisms of strong and weak solitons are discussed in detail. This work provides insights into the binding mechanism and internal dynamics of BSs.

Synchronous and asynchronous pulsating dual solitons in lasers.

Pulsating solitons are intriguing objects in laser physics and nonlinear science. Recently, emerging works on the pulsating multi-solitons have raised interest in interactions and synchronizations within multiple breathers. However, with their separation of the order of nanoseconds, the evolution and underlying dynamics of multiple pulsating solitons remain uncharted. In this work, we bring initial insights into the pulsating dual-soliton (PDS) with a separation of three orders of magnitude of the pulse duration. Chaotic, synchronous, and asynchronous pulsations are revealed to be controlled by the pump power. Specifically, two solitons can pulsate synchronously in the form of a frozen limit cycle. The asynchronous PDS at a high pump power brings the rotating limit cycle in the phase space. Unveiling the evolutionary dynamics of PDS, this work has potential in all-optical storage, signal encoding, and time division multiplexing communications.

In2S3 nanoparticles coupled to In-MOF nanorods: The structural and electronic modulation for synergetic photocatalytic degradation of Rhodamine B.

Enhancing photocatalytic performance via electronic modulation have attracted much attention for synergetic photocatalytic degradation of antibiotic pollutant. In this study, a new hetero-structured system is raised, which comprises In2S3 coupled to In-MOF and operates as an efficient photocatalyst for RhB degradation. The formation of hetero-structure and occurred electron modulation of In2S3/In-MOF hybrid was confirmed by relevant characterizations. Surprisingly, the In2S3/In-MOF hybrid represented enhanced photocatalytic ability over In-MOF. The photocatalysis of Rhodamine B in presence of In2S3/In-MOF hybrid has achieved 92.2 % degradation.

Use of Radial Artery Grafts for Coronary Artery Bypass Grafting.

Coronary artery bypass grafting (CABG) is the primary surgical treatment for coronary artery disease (CAD). However, long-term clinical practice has confirmed the poor long-term patency of saphenous vein grafts (SVG), prompting surgeons to investigate alternatives, such as the use of radial artery (RA) grafts. In this report, we review and discuss the current status of radial artery application during CABG and current controversies in the field. Ultimately, evidence indicates that RA-CABG is associated with good long-term patency and is suitable for patients with severe stenosis. However, the compensatory capacity of the ulnar artery should be assessed prior to RA harvesting. Given that the RA is prone to spasms, routine application of calcium channel blockers is recommended. Several studies also have indicated that sequential grafting is an effective method for maximizing radial artery application and that patency rates are similar for the radial artery and right internal mammary artery. In contrast, the use of the bilateral internal mammary arteries is technically more demanding and exhibits a significant volume-outcome relationship. The decision to use the right internal mammary artery or radial artery should be based on individual patient characteristics and the experience of the surgical team.

Periodic attraction and repulsion within the tight-bound π-phase soliton molecule.

In the over-pumped dissipative system, the single pulse is prone to split into multi-soliton modes, among which the soliton molecule (SM) comprising two pulses has attracted much interest recently. In this Letter, the tight-bound SM with the π-phase-difference, a soliton pair predicted to be unstable observed in fiber lasers, is found to have oscillating separation with excellent stability. For the first time, to the best of our knowledge, we reveal the mechanism of the π-phase SM to circumvent the irreversible repulsion and the role of dispersive waves on the SM. During the periodic propagation, the destructive interference between solitons produces the repulsion while the dispersive waves give rise to the attractive force, leading to the dynamic oscillating behavior of the SM. The numerical simulation reproduces the experimental observation and offers panoramic insights into the nonlinear interactions between multiple components in dissipative systems.

Graphene-tuned EIT-like effect in photonic multilayers for actively controlled light absorption of topological insulators.

As newly emerging nanomaterials, topological insulators with unique conducting surface states that are protected by time-reversal symmetry present excellent prospects in electronics and photonics. The active control of light absorption in topological insulators are essential for the achievement of novel optoelectronic devices. Herein, we investigate the controllable light absorption of topological insulators in Tamm plasmon multilayer systems composed of a Bi1.5Sb0.5Te1.8Se1.2 (BSTS) film and a dielectric Bragg mirror with a graphene-involved defect layer. The results show that an ultranarrow electromagnetically induced transparency (EIT)-like window can be generated in the broad absorption spectrum. Based on the EIT-like effect, the Tamm plasmon enhanced light absorption of topological insulators can be dynamically tuned by adjusting the gate voltage on graphene in the defect layer. These results will pave a new avenue for the realization of topological insulator-based active optoelectronic functionalities, for instance light modulation and switching.

Lab on D-shaped fiber excited via azimuthally polarized vector beam for surface-enhanced Raman spectroscopy.

We present a method for Raman examination using a silver-nanoparticles (Ag-NPs) coated D-shaped fiber (DSF) internally excited via an in-fiber azimuthally polarized beam (APB) generated by an acoustically induced fiber grating. Simulation results show that an electric-field intensity enhancement factor can be effectively improved under APB excitation compared with the linear polarization beam (LPB) excitation, because the strong gap-mode is uniformly generated between two adjacent Ag NPs on the surface of the DSF planar side. Experimental results show that the Raman signal intensity of the methylene blue (MB) detected by DSF in the case of APB excitation is ∼4.5 times as strong as that of LPB excitation, and the Raman detection sensitivity is ∼10-9 M. The time stability of this method is also tested to be guaranteed.

Plasmon-enhanced linear and second-order surface nonlinear optical response of silver nanoparticles fabricated using a femtosecond pulse.

We present the plasmon-enhanced linear and second-order surface nonlinear optical response of silver nanoparticles (Ag NPs) fabricated using a femtosecond pulse. Theoretical analysis indicates Ag NPs with a diameter of ∼100 nm have excellent linear response within the visible band, and the electric field intensity enhancement factor reaches ∼105 under excitation of continuous light of 632.8 nm. Meanwhile, the simulation result of second-order surface nonlinear optical response shows that the second harmonic conversion efficiency of the Ag NPs dimer is two orders of magnitude higher than that of a single Ag NP, under excitation of a femtosecond pulse. In experiment, the linear response of Ag NPs is examined using surface-enhanced Raman spectroscopy (SERS) with a Raman enhancement factor of ∼1.7 × 1010, revealing the excellent linear optical response of Ag NPs. Moreover, the spectra of the second harmonic can be measured clearly under conditions of an average pump power of 40 µW, revealing the excellent second-order surface nonlinear optical response of Ag NPs.

A pulsewidth measurement technology based on carbon-nanotube saturable absorber.

We demonstrate a proof-of-concept saturable absorption based pulsewidth measurement (SAPM) by exploring the intensity dependent nonlinear transmission (i.e., saturable absorption) of low-dimensional material (LDM) carbon nanotubes. A minimum pulse energy of 75 fJ is experimentally detected with an average-power-peak-power product (Pav⋅ Ppk) of 5.44×10-7 W2 near 1550 nm. A minimum detectable pulse energy of 10 fJ with a Pav⋅ Ppk of 1.3×10-9 W2 is estimated with further optimization. The nanometer-level thickness and femtosecond-level decay time of LDMs allow ultrafast light interaction on a very small footprint, which potentially supports chip-scale characterization of ultrafast pulses with minimum distortion.

Induced reflection in Tamm plasmon systems.

We present an induced reflection response analogue to electromagnetically induced transparency (EIT) in a novel Tamm plasmon system, consisting of a thin metal film and a Bragg grating with a defect layer. The results show that an induced narrow peak can be generated in the original broad reflection dip, which is attributed to the coupling and interference between the Tamm plasmon and defect modes in the grating structure. It is found that the EIT-like induced reflection is strongly dependent on the thickness of defect layer, grating period number between the metal and defect layers, thickness of Bragg grating layer, refractive index of defect layer, and thickness of metal film. Additionally, the induced reflection can be dynamically tuned by adjusting the angle of incident light. The numerical simulations agree extremely well with theoretical calculations. The coupling strength between the Tamm plasmon and defect modes is determined by the above parameters. These results will provide a new avenue for light field control and devices in multilayer photonic systems.