Underlying Mechanism of Lysosomal Membrane Permeabilization in CNS Injury: A Literature Review.

Lysosomes play a crucial role in various intracellular pathways as their final destination. Various stressors, whether mild or severe, can induce lysosomal membrane permeabilization (LMP), resulting in the release of lysosomal enzymes into the cytoplasm. LMP not only plays a pivotal role in various cellular events but also significantly contributes to programmed cell death (PCD). Previous research has demonstrated the participation of LMP in central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid hemorrhage (SAH), and hypoxic-ischemic encephalopathy (HIE). However, the mechanisms underlying LMP in CNS injuries are poorly understood. The occurrence of LMP leads to the activation of inflammatory pathways, increased levels of oxidative stress, and PCD. Herein, we present a comprehensive overview of the latest findings regarding LMP and highlight its functions in cellular events and PCDs (lysosome-dependent cell death, apoptosis, pyroptosis, ferroptosis, and autophagy). In addition, we consolidate the most recent insights into LMP in CNS injury by summarizing and exploring the latest advances. We also review potential therapeutic strategies that aim to preserve LMP or inhibit the release of enzymes from lysosomes to alleviate the consequences of LMP in CNS injury. A better understanding of the role that LMP plays in CNS injury may facilitate the development of strategic treatment options for CNS injury.

Exploring the role of parthanatos in CNS injury: Molecular insights and therapeutic approaches.

BACKGROUND: Central nervous system (CNS) injury causes severe organ damage due to both damage resulting from the injury and subsequent cell death. However, there are currently no effective treatments for countering the irreversible loss of cell function. Parthanatos is a poly (ADP-ribose) polymerase 1 (PARP-1)-dependent form of programmed cell death that is partly responsible for neural cell death. Consequently, the mechanism by which parthanatos promotes CNS injury has attracted significant scientific interest. AIM OF REVIEW: Our review aims to summarize the potential role of parthanatos in CNS injury and its molecular and pathophysiological mechanisms. Understanding the role of parthanatos and related molecules in CNS injury is crucial for developing effective treatment strategies and identifying important directions for future in-depth research. KEY SCIENTIFIC CONCEPTS OF REVIEW: Parthanatos (from Thanatos, the personification of death according to Greek mythology) is a type of programmed cell death that is initiated by the overactivation of PARP-1. This process triggers a cascade of reactions, including the accumulation of poly(ADP-ribose) (PAR), the nuclear translocation of apoptosis-inducing factor (AIF) after its release from mitochondria, and subsequent massive DNA fragmentation caused by migration inhibitory factor (MIF) forming a complex with AIF. Secondary molecular mechanisms, such as excitotoxicity and oxidative stress-induced overactivation of PARP-1, significantly exacerbate neuronal damage following initial mechanical injury to the CNS. Furthermore, parthanatos is not only associated with neuronal damage but also interacts with various other types of cell death. This review focuses on the latest research concerning the parthanatos cell death pathway, particularly considering its regulatory mechanisms and functions in CNS damage. We highlight the associations between parthanatos and different cell types involved in CNS damage and discuss potential therapeutic agents targeting the parthanatos pathway.

Idiopathic short stature and scoliosis in children treated with growth hormone.

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study. A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery. In the cross-sectional study, there was an unexpectedly higher prevalence of scoliosis (33.1% (681/2,053) vs 8.52% (350/4,106)) in children with idiopathic short stature compared with controls (odds ratio 3.722; p < 0.001), although most cases were mild. In the longitudinal study, children with idiopathic short stature had a higher risk of the development and progression of scoliosis than the controls. Among children with idiopathic short stature without scoliosis at baseline, treatment with growth hormone significantly increased the risk of developing scoliosis (p = 0.015) and the need for bracing (p < 0.001). Among those with idiopathic short stature and scoliosis at baseline, treatment with growth hormone did not increase the risk of progression of the scoliosis, the need for bracing, or surgery. The impact of treatment with growth hormone on scoliosis in children with idiopathic short stature was considered controllable. However, physicians should pay close attention to the assessment of spinal curves in these children.

Enhancing oxygen/moisture resistance of quantum dots by short-chain, densely cross-linked silica glass network.

Quantum dots (QDs) are facing significant photoluminescence degradation in moisture environment. In QDs-silicone composites, the poor water resistance of silicone matrix makes it easy for water and oxygen molecules to erode QDs. To tackle this issue, we proposed a new QDs protection strategy by introducing short-chain silica precursors onto the QDs' surface, so that a dense silica passivation layer could be formed onto the QDs nanoparticles. Sol-gel method based on 3-aminopropyl triethoxysilane (APTES), 3-mercaptopropyl trimethoxysilane (MPTMS), and 3-mercaptopropyl triethoxysilane (MPTES) were adopted to prepare the uniform and crack-free QDs-silica glass (QD-glass). Because of the crosslinking of short-chain precursors, the formed silica glass possesses 38.6% smaller pore width and 68.6% lower pore volume than silicone, indicating its denser cross-linked network surrounding QDs. After 360 h water immersion, the QDs-glass demonstrated a 6% enhancement in red-light peak intensity, and maintained a stable full width at half maximum (FWHM) and peak wavelength, proving its excellent water-resistant ability. However, the conventional QDs-silicone composites not only showed a decrease of 75.3% in red-light peak intensity, but also a broadened FWHM and a redshifted peak wavelength after water immersion. QDs-glass also showed superior photostability after 132 h exposure to blue light. Red-light peak intensity of QDs-glass remained 87.3% of the initial while that of QDs-silicone decreased to 19.8%. And the intensity of QDs-glass dropped to 62.3% of that under 20 °C after thermal treatment of 160 °C. Besides, under increasing driving currents, the light conversion efficiency drop of QDs-glass is only one fifth that of QDs-silicone. Based on the QDs-glass, the white light-emitting diodes was achieved with a high luminous efficiency of 126.5 lm W-1and a high color rendering index of 95.4. Thus, the newly proposed QD-glass has great significance in guaranteeing the working reliability of QDs-converted devices against moisture and high-power environment.

Silencing of Vangl2 attenuates the inflammation promoted by Wnt5a via MAPK and NF-κB pathway in chondrocytes.

BACKGROUND: The Wnt planar cell polarity (PCP) pathway is implicated in osteoarthritis (OA) both in animals and in humans. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the orientation and alignment of chondrocytes in the growth plate. However, its functional roles in OA still remain undefined. Here, we explored the effects of Vangl2 on OA chondrocyte in vitro and further elucidated the molecular mechanism of silencing Vangl2 in Wnt5a-overexpressing OA chondrocytes. METHODS: Chondrocytes were treated with IL-1ß (10 ng/mL) to simulate the inflammatory microenvironment of OA. The expression levels of Vangl2, Wnt5a, MMPs, and related proinflammatory cytokines were measured by RT-qPCR. Small interfering RNA (siRNA) of Vangl2 and the plasmid targeting Wnt5a were constructed and transfected into ATDC5 cells. Then, the functional roles of silencing Vangl2 in the OA chondrocytes were investigated by Western blotting, RT-qPCR, and immunocytochemistry (ICC). Transfected OA chondrocytes were subjected to Western blotting to analyze the relationship between Vangl2 and related signaling pathways. RESULTS: IL-1ß induced the production of Vangl2, Wnt5a, and MMPs in a time-dependent manner and the significantly increased expression of Vangl2. Vangl2 silencing effectively suppressed the expression of MMP3, MMP9, MMP13, and IL-6 at both gene and protein levels and upregulated the expression of type II collagen and aggrecan. Moreover, knockdown of Vangl2 inhibited the phosphorylation of MAPK signaling molecules (P38, ERK, and JNK) and P65 in Wnt5a-overexpressing OA chondrocytes. CONCLUSIONS: For the first time, we demonstrate that Vangl2 is involved in the OA process. Vangl2 silencing can notably alleviate OA progression in vitro by inhibiting the expression of MMPs and increasing the formation of the cartilage matrix and can inhibit the proinflammatory effects of Wnt5a via MAPK and NF-κB pathway. This study provides new insight into the mechanism of cartilage inflammation.

Effect of refractive index of packaging materials on the light extraction efficiency of COB-LEDs with millilens array.

Lens arrays are introduced to diminish the total internal reflection (TIR) that happens at chip-encapsulant and encapsulant-air interfaces of chip-on-board light-emitting diodes (COB-LEDs), so as to improve the light extraction efficiency (LEE) of the COB-LEDs. However, the LEE of COB-LEDs with lens array depends on the refractive index of the encapsulant layer nencap and lens array nlens, which was rarely concerned so far. Optical simulations based on a Monte Carlo ray tracing method, and experiments were conducted to investigate the effect of nencap and nlens on the LEE of COB-LEDs with millilens array. The simulated results show that the TIR at chip-encapsulant, encapsulant-lens, and lens-air interfaces can be significantly diminished by regulating the nencap and nlens, and the LEE of COB-LEDs decreases as the refractive difference of encapsulant layer and lens array |nlens-nencap| increases. Compared to the COB-LEDs with only a flat encapsulant layer, the LEEs of blue and white COB-LEDs with nlens=nencap=nITO=2 are enhanced by 246.2% and 50.6%, where nITO is the refractive index of the top layer of the conventional LED chip. The experimental results agree well with the simulated results with normalized LEE deviation within 7.3%.