Galectin-3 inhibition reduces fibrotic scarring and promotes functional recovery after spinal cord injury in mice.

BACKGROUND: In the context of spinal cord injury (SCI), infiltrating macrophages assume prominence as the primary inflammatory cells within the lesion core, where the fibrotic scar is predominantly orchestrated by platelet-derived growth factor receptor beta (PDGFRß+) fibroblasts. Galectin-3, a carbohydrate-binding protein of the lectin family, is notably expressed by infiltrating hematogenous macrophages and mediates cell-cell interactions. Although Galectin-3 has been shown to contribute to the endocytic internalization of PDGFRß in vitro, its specific role in driving fibrotic scar formation after SCI has not been determined. METHODS: We employed a crush mid-thoracic (T10) SCI mouse model. Galectin-3 inhibition after SCI was achieved through intrathecal injection of the Galectin-3 inhibitor TD139 or in situ injection of lentivirus carrying Galectin-3-shRNA (Lv-shLgals3). A fibrosis-induced mice model was established by in situ injection of platelet-derived growth factor D (PDGFD) or recombinant Galectin-3 (rGalectin-3) into the uninjured spinal cord. Galectin-3 internalization experiments were conducted in PDGFRß+ fibroblasts cocultured in conditioned medium in vitro. RESULTS: We identified the spatial and temporal correlation between macrophage-derived Galectin-3 and PDGFRß in fibroblasts from 3 to 56 days post-injury (dpi). Administration of TD139 via intrathecal injection or in situ injection of Lv-shLgals3 effectively mitigated fibrotic scar formation and extracellular matrix deposition within the injured spinal cord, leading to better neurological outcomes and function recovery after SCI. Furthermore, the fibrosis-inducing effects of exogenous PDGFD in the uninjured spinal cord could be blocked by TD139. In vitro experiments further demonstrated the ability of PDGFRß+ fibroblasts to internalize Galectin-3, with Galectin-3 inhibition resulting in reduced PDGFRß expression. CONCLUSIONS: Our finding underscores the pivotal role of macrophage-derived Galectin-3 in modulating the sustained internalized activation of PDGFRß within fibroblasts, providing a novel mechanistic insight into fibrotic scarring post-SCI.

Evaluation of the prognosis in patients with small-cell lung cancer treated by chemotherapy using tumor shrinkage rate-based radiomics.

BACKGROUND: Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. METHODS: We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan-Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. RESULTS: The TSR cutoff was identified to be - 6.6%. Median PFS and OS were longer in the group with a TSR < -6.6% than in the group with a TSR ≥ - 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < - 6.6% than when it was > - 6.6%. Brain metastasis-free survival was better in the group with a TSR < - 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS. CONCLUSIONS: The TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.

Surface Gradient Desodiation Chemistry in Layered Oxide Cathode Materials.

Sodium-ion batteries (SIBs) as a promising technology for large-scale energy storage have received unprecedented attention. However, the cathodes in SIBs generally suffer from detrimental cathode-electrolyte interfacial side reactions and structural degradation during cycling, which leads to severe capacity fade and voltage decay. Here, we have developed an ultra-stable Na0.72Ni0.20Co0.21Mn0.55Mg0.036O2 (NCM-CS-GMg) cathode material in which a Mg-free core is encapsulated by a shell with gradient distribution of Mg using coprecipitation method with Mg-hysteretic cascade feedstock followed by calcination. From the interior to outer surface of the shell, as the content of electrochemically inactive Mg gradually increases, the Na+ deintercalation amount gradually decreases after charged. Benefiting from this surface gradient desodiation, the surface transition metal (TM) ion migration from TM layers to Na layers is effectively inhibited, thus suppressing the layered-to-rock-salt phase transition and the resultant microcracks. Besides, the less formation of high-valence TM ions on the surface contributes to a stable cathode-electrolyte interface. The as-prepared NCM-CS-GMg exhibits remarkable cycling life over 3000 cycles with a negligible voltage drop (0.127 mV per cycle). Our findings highlight an effective way to developing sustainable cathode materials without compromising on the initial specific capacity for SIBs.

Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury.

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment.

Realizing High Capacity and Zero Strain in Layered Oxide Cathodes via Lithium Dual-Site Substitution for Sodium-Ion Batteries.

Sodium-ion batteries have garnered unprecedented attention as an electrochemical energy storage technology, but it remains challenging to design high-energy-density cathode materials with low structural strain during the dynamic (de)sodiation processes. Herein, we report a P2-layered lithium dual-site-substituted Na0.7Li0.03[Mg0.15Li0.07Mn0.75]O2 (NMLMO) cathode material, in which Li ions occupy both transition-metal (TM) and alkali-metal (AM) sites. The combination of theoretical calculations and experimental characterizations reveals that LiTM creates Na-O-Li electronic configurations to boost the capacity derived from the oxygen anionic redox, while LiAM serves as LiO6 prismatic pillars to stabilize the layered structure through suppressing the detrimental phase transitions. As a result, NMLMO delivers a high specific capacity of 266 mAh g-1 and simultaneously exhibits the nearly zero-strain characteristic within a wide voltage range of 1.5-4.6 V. Our findings highlight the effective way of dual-site substitution to break the capacity-stability trade-off in cathode materials for advanced rechargeable batteries.

Molecular characteristics, oncogenic roles, and relevant immune and pharmacogenomic features of NEK2 in gastric cancer.

Gastric cancer (GC) is the most common form of gastrointestinal cancer, with a high mortality rate and limited treatment options. High levels of NEK2 are associated with malignant progression and a poor prognosis in several tumors; however, the role of NEK2 in GC remains unclear. We aimed to explore the potential role of NEK2 in the oncogenesis of GC and in the shaping of the tumor microenvironment (TME). The expression levels of NEK2 were analyzed using immunohistochemistry and real-time quantitative polymerase chain reaction. We found that NEK2 expression was upregulated in GC and was a predictor of a poor prognosis. Based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment and gene set enrichment analyses, multiple tumor pathways were hyperactivated in patients with high NEK2 mRNA expression. Immunological characteristics indicated that NEK2 upregulation might lead to decreased immune cell infiltration and weakened immune activity in the cancer immunity cycle. Additionally, higher frequencies of amplifications and deletions were observed in the high NEK2 expression subpopulation. Based on the TME classification, patients with high expression of NEK2 were more susceptible to targeted therapy with drugs targeting the cell cycle and DNA replication. Following verification, a NEK2-derived genomic model reliably predicted the patient prognosis; A nomogram (radiation therapy, tumor/node/metastasis staging, and the NEK2-derived risk score) was used to better estimate an individual's survival probability. In summary, our findings indicate that NEK2 plays a vital role in the tumorigenesis of GC.

CD146 is closely associated with the prognosis and molecular features of osteosarcoma: Guidance for personalized clinical treatment.

Background: Osteosarcoma (OSA), a focus for orthopedic surgeons, always results in severe death due to metastasis. CD146 is severely expressed in several tumors, indicating its potential as a biomarker for OSA. Method: Two OSA cohorts were enrolled in this study. A Therapeutically Applicable Research to Generate Effective Treatments-Osteosarcoma (TARGET-OS) cohort was used as a training cohort, and GSE21257 was used as the external validation cohort. The R package "limma" was used to discriminate the differentially expressed genes among CD146-high and CD146-low patients and was further annotated by the enriched signaling pathways. The R package MOVICS was used to evaluate immune infiltration and the response to chemotherapy and immunotherapy. All statistical analyses were performed by R version 4.0.2, and p < 0.05 was considered statistically significant. Result: CD146 plays an important role in promoting the progression, invasion, and metastasis of several tumors. In the current study, we first revealed an integrative unfavorable prognosis in patients with tumors (p < 0.01, HR: 1.10, 95% CI: 1.07-1.14). CD146 is tightly correlated with m5C RNA methylation modification genes in OSA. Furthermore, we revealed that CD146 acts as an oncogene in OSA patients and is linked to poor prognosis in both the TARGET-OS cohort (p = 0.019, HR: 2.61, 95% CI: 1.171-5.834) and the GSE21257 cohort (p = 0.005, HR: 3.61, 95% CI: 1.474-8.855), with a total of 137 patients, regardless of whether they were adjusted for clinical pathological features. Highly-expressed CD146 impacts the signaling pathways of cytokine‒cytokine receptor interactions and is associated with the high infiltration of immunocytes. Moreover, patients with high CD146 expression were more likely to be sensitive to anti-PD-1 immunotherapy, while patients with low expression of CD146 were more likely to be sensitive to cisplatin and doxorubicin chemotherapy. Conclusion: Overall, CD146 is an independent prognostic factor for OSA patients and can help doctors select clinical treatment strategies.

Coexistence of multiple microcombs in monochromatically pumped Si3N4 microresonators.

We experimentally demonstrate that multiple microcombs can coexist in monochromatically pumped Si3N4 microresonators. By pumping around the mode crossing using a CW laser with mixed polarization, three types of coherent microcombs are generated simultaneously: (i) TE-polarized soliton microcomb; (ii) TM-polarized Turing rolls microcomb; and (iii) cross-phase-modulation-induced TM-polarized microcomb. It is proved that the type-(iii) microcomb shares the same comb line spacing with the type-(i) microcomb although the free spectral ranges of TE and TM modes are different. In addition, a 22.95-GHz signal is extracted from a ∼100-GHz microresonator by heterodyning the TE and TM comb lines, and phase noise analysis reveals their coherence characteristics.

Building Homogenous Li2 TiO3 Coating Layer on Primary Particles to Stabilize Li-Rich Mn-Based Cathode Materials.

Li-rich Mn-based oxides (LRMOs) are promising cathode materials for next-generation lithium-ion batteries (LIBs) with high specific energy (≈900 Wh kg-1 ) because of anionic redox contribution. However, LRMOs suffer from issues such as irreversible release of lattice oxygen, transition metal (TM) dissolution, and parasitic cathode-electrolyte reactions. Herein, a facile, scalable route to build homogenous and ultrathin Li2 TiO3 (LTO) coating layer on the primary particles of LRMO through molten salt (LiCl) assisted solid-liquid reaction between TiO2 and Li1.08 Mn0.54 Co0.13 Ni0.13 O2 is reported. The prepared LTO-coated Li1.08 Mn0.54 Co0.13 Ni0.13 O2 (LTO@LRMO) exhibits 99.7% capacity retention and 95.3% voltage retention over 125 cycles at 0.2 C, significantly outperforming uncoated LRMO. Combined characterizations of differential electrochemical mass spectrometry, in situ X-ray diffraction, and ex situ X-ray photoelectron spectroscopy evidence significantly suppressed oxygen release, phase transition, and interfacial reactions. Further analysis of cycled electrodes reveals that the LTO coating layer inhibits TM dissolution and prevents the lithium anode from TM crossover effect. This study expands the primary particle coating strategy to upgrade LRMO cathode materials for advanced LIBs.

Case report and literature review: Primary leiomyosarcoma of the bone in the trochanteric region of the femur.

Background: Primary leiomyosarcoma of the bone (LMSB) is an extremely rare, invasive, and highly destructive primary osteosarcoma with limited treatment options and poor prognosis. Only a few case reports of LMSB have been described because of its rarity. Therefore, clinicians have a limited understanding of its diagnosis, treatment, and prognosis, and the final diagnosis depends on histopathological findings. In this report, we describe a rare case of primary LMSB in the trochanteric region of the femur. Reporting this case may increase the dissemination and understanding of information regarding LMSB and provide a reference for the diagnosis and treatment of similar cases. Case presentation: A 63-year-old woman presented with pain and limited movement of the left hip, which had lasted for 3 months, with no history of trauma or illness. Plain radiography and computed tomography revealed a solitary osteolytic lesion in the trochanteric area of the left femur with focal cortical destruction. Magnetic resonance imaging findings suggested invasion of the lesion into the bone cortex, forming a soft tissue mass, although no distant positive findings were observed on a whole-body bone scan. A bone tumor puncture biopsy was performed to obtain a final diagnosis, and histopathological evaluation revealed left femoral intertrochanteric leiomyosarcoma, classified as G1T2M0 and staged as IB (extracompartmental low-grade malignant) according to the Enneking staging system. Thus, we performed extensive debridement and left hip arthroplasty. Postoperative chemotherapy was administered, and the patient was followed up for 4 years. Four years later, the patient's left hip pain had resolved, joint activity was good, and no signs of recurrence or distant metastasis of the bone tumor were noted. Conclusion: For proximal femoral Enneking stage IB LMSB, extensive tumor resection combined with tumor prosthesis replacement may be an effective treatment method to prolong the patient's lifespan and to restore joint function.

Multi-octave linearized RF/photonic link based on orthogonal modulation and optimized demodulation.

In this Letter, we propose and demonstrate a multi-octave linearized analog radio-frequency (RF)/photonic link with orthogonal modulation and optimized demodulation. In our proposed link, the DC-reserved (DCR) digital method is utilized in a parallel Mach-Zehnder-modulator scheme to greatly improve the tolerance to the in-phase/quadrature amplitude imbalance and Q-path DC error, which inevitably exist during digital processing. The fault tolerance and transmission performance of the link are theoretically analyzed and experimentally verified. Compared with the traditional digital-signal-processing method, higher signal-to-distortion ratios can be achieved by the DCR method when the amplitude imbalance and DC errors are considered. As a result, the SFDR2 and SFDR3 (spurious-free dynamic ranges) of our system are measured to be 103.74dB⋅Hz1/2 and 116.31dB⋅Hz2/3, respectively. Furthermore, the linearization of the link is demonstrated by testing the RF signals with various frequencies, which proves the potential in broadband applications.

High-SFDR 100.8km ROF link with optical homodyne detection and genetic-algorithm-assisted digital demodulation.

Radio-over-fiber (ROF) link based on phase modulation and coherent detection has been widely proposed for linear transmission. Nowadays, there are increasing demands for long-distance analog radio-frequency (RF) signal transmission, as radars and broadcast systems. In this paper, a high spurious-free-dynamic-range (SFDR) analog coherent ROF link based on optical homodyne detection and genetic-algorithm-assisted digital demodulation is proposed and experimentally investigated. The ROF link is designed for transmitting RF signals ranging from 500 kHz to 100 MHz over a long-distance fiber under the environment of wide temperature. We test the link performance by transmitting different groups of two-tone signals (580 kHz and 600 kHz, 9 MHz and 10 MHz, 49 MHz and 50 MHz, 99 MHz and 100 MHz) over a 100.8-km single-mode fiber (SMF) under the temperature varying from -40°C to 70°C, the shot-noise-limited SFDR of the link are measured to be greater than 122 dB·Hz2/3.

Frequency-demultiplication OEO for stable millimeter-wave signal generation utilizing phase-locked frequency-quadrupling.

A novel scheme for the generation and stabilization of the millimeter-wave (mmW) signal employing a frequency-demultiplication optoelectronic oscillator (FD-OEO) has been theoretically analyzed and experimentally demonstrated. The FD-OEO can keep sustaining without optical first-order sidebands, which would help to simplify the photonic-assisted frequency multiplication process and provide a wide frequency compensation range for the mmW system simultaneously. The stability of the generated 40-GHz mmW signal reaches 1.38 × 10-12 at the average time of 100s. Besides, the measured single-sideband phase noise of the generated mmW signal exhibits as low as -103 dBc/Hz at 10-kHz offset frequency, maintaining a spurious level of -97 dBc.

HeLa cell adhesion on various collagen-grafted surfaces.

Cell adhesion is important to develop cell microarrays and biocompatible materials. Collagen has been reported to be able to improve cell adhesion. In this paper, two collagen coating methods (collagen grafted directly on the substrate and chitosan-modified substrate) were carried out, on which the adhesive behaviors of HeLa cells were studied. An atomic force microscope and a surface potential meter were used to characterize morphologies and electric polarization of these surfaces. It was found that surface electric polarization and the its durability and surface topography were key factors to cell adhesion. Collagen (1 mg/mL) grafted on 1% chitosan-modified surface showed the best adhesion of HeLa cell. This work might be helpful to the practical application of cell microarray chips.