Oscillatory potential findings in patients with acute ischaemic central retinal vein occlusion.

AIMS: To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO). METHODS: 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG. RESULTS: A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1-4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes. CONCLUSION: The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.

Mendelian randomization of individual sleep traits associated with major depressive disorder.

BACKGROUND: Observational studies have shown that individual sleep traits habits are potential risk factors for major depression. However, it is not known whether there is a causal relationship between individual sleep traits habits such as continuous sleep duration, short sleep duration, short sleep duration, insomnia, nap during the day, snoring, and major depression. In this study, Mendelian randomization (MR) was used to predict major depressive disorder (MDD) in individuals sleep traits habits. METHODS: Data were obtained from the genome-wide association study (GWAS). Nine MR analysis methods were used: Inverse Variance Weighted (IVW) [fixed effects/multiplicative random effects], simple mode, simple mode, weighted mode, simple median, weighted median, penalised weighted median, and MR-Egger, MR Egger (bootstrap). IVW was used as the main analysis method for the MR analysis of two samples, and the other methods were used as supplements. RESULTS: The results obtained through the IVW method supported a causal relationship between sleep duration and decreased risk of MDD (odds ratio, ORivw: 0.998; 95 % CI: 0.996-0.999, P<0.001). Two-Sample MR, results showed that short sleep duration has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.179; 95 % CI: 1.108-1.255, P<0.001). However, there were no sufficient evidence supported that long sleep duration has a causal effect on the decreased risk of MDD (odds ratio, ORivw: 0.991; 95 % CI: 0.924-1.062, P = 0.793). A significant causal relationship between insomnia and increased risk of MDD was observed (OR: 1.233; 95 % CI: 1.214-1.253, P<0.001). Interestingly, our study also found that daytime napping has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.519; 95 % CI: 1.376-1.678, P<0.001). The present results did not show a significant causal relationship between snoring and the risk of MDD (ORivw: 1.000; 95 % CI: 0.998-1.002, P = 0.906). Obstructive sleep apnea (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) and morning person (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) have no causal effect on the increased risk of MDD. LIMITATIONS: The study could not ascertain whether there were genetic differences among different ethnicities, nations, and regions, as it only included participants of European ancestry. CONCLUSIONS: In summary, our research provides genetic evidence for the relationship between individual sleep traits (short sleep duration, insomnia, daytime napping) and the increased risk of MDD. Interventions targeting lifestyle factors may reduce the risk of MDD.

Effect of gradient pressure therapy on the prevention of chemotherapy-induced peripheral neuropathy in patients with breast cancer.

PURPOSE: To investigate the effect of gradient pressure therapy on the prevention of chemotherapy-induced peripheral neuropathy (CIPN) and improvement in activities of daily living (ADL) in patients with breast cancer. METHODS: Eighty female patients with breast cancer treated at Tangshan People's Hospital between October 2022 and July 2023 were selected as research participants and divided into control and intervention, with 40 patients in each group. The control group received routine treatment and care, whereas the intervention group received gradient pressure therapy based on routine treatment and care. Incidence of peripheral neuropathy and the degree of impact on ADL between the two groups were compared after the intervention for cycles 2, 4, and 6. RESULTS: There was no significant difference in the general information between the two groups (P > 0.05). After two intervention cycles, there was no significant difference in the incidence of CIPN, various dimensions of Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (CIPNAT), and total scores between the two groups (P > 0.05). After four intervention cycles, the two groups had a statistically significant difference in the incidence of CIPN, sensory dimension, general activity dimension, and total CIPNAT score (P < 0.05). After six intervention cycles, there was a significant difference in the incidence of CIPN, sensory dimension, fine activity dimension, general activity dimension, and total CIPNAT score between the two groups (P < 0.05), while there was no significant difference in the other dimensions (P > 0.05). CONCLUSIONS: Gradient pressure therapy can effectively prevent or alleviate peripheral neuropathy in patients with breast cancer undergoing chemotherapy and improve their ability to perform ADL. Thus, it is safe, effective, and worthy of clinical application. TRIAL REGISTRATION: RMYY-LLKS-2022-054.

Largely Improved Creep Resistance and Thermal-Aging Stability of Eco-Friendly Polypropylene High-Voltage Insulation by Long-Chain Branch-Induced Interfacial Constraints.

Polypropylene (PP)-based composites have attracted numerous attention as a replacement of prevailing cross-linked polyethylene (XLPE) for high-voltage insulation due to their ease of processing, recyclability, and excellent electrical performance. However, the poor resistances against high-temperature creep and thermal aging are obstacles to practical applications of PP-based thermoplastic high-voltage insulation. To address these problems, in this Letter, we synthesized an impact polypropylene copolymer (IPC) containing multifold long-chain branched (LCB) structures in phases, especially the interfaces between the PP matrix and the rubber phase. The results indicated that the structural stability of LCBIPC was significantly enhanced under extreme conditions. In comparison to IPC (without LCB structures), 24.1% less creep strain and 75.2% less unrecoverable deformation are achieved in LCBIPC at 90 °C. In addition, the thermal aging experiments were performed at 135 °C for 48 and 88 days for IPC and LCBIPC, respectively. The results show that the resistance against thermal aging was also enhanced in LCBIPC, which showed a 133% longer thermal aging life compared to IPC. Further results revealed that the interfacial layer between the PP matrix and the rubber phase was constructed in LCBIPC. The two phases are tightly linked by chemical bonds in LCB structures, leading to enforced constraints of the rubber phase at the micro level and better resistance performance against creep and thermal aging at the macro level. Evidently, the reported eco-friendly LCBIPC thermoplastic insulation shows great potential for applications in high-voltage cable insulation.

Therapeutic effects of compression therapy on taxane-induced peripheral neuropathy incidence, negative emotions, and sleep disorders in patients with breast cancer.

PURPOSE: To explore the effects of compression therapy on chemotherapy-induced peripheral neuropathy (CIPN), anxiety, depression, and sleep disorders in breast cancer patients administered taxanes. METHODS: Eighty patients with breast cancer undergoing chemotherapy at Tangshan People's Hospital between October 2022 and July 2023 were randomly divided into control (n = 40) and intervention (n = 40) groups. The control group received routine care, while intervention group received compression therapy in addition to routine care (30 min before the infusion of chemotherapy drugs, patients wore surgical gloves on their hands that were one size smaller than the appropriate size and elastic socks on their feet until 30 min after the infusion). The incidence of CIPN, anxiety, depression, and sleep scores, were compared between these groups before and after compression therapy during chemotherapy cycles 2, 4, and 6. RESULTS: The general characteristics did not differ significantly between the groups (P > 0.05). The CIPN incidence, anxiety and depression scores, and sleep scores also did not differ significantly between the two groups before and after the intervention period (P > 0.05). After the fourth and sixth cycles of intervention, the incidence of CIPN (≥ 1 and ≥ 2), anxiety and depression scores, and sleep scores were significantly lower in the intervention group than in the control group (P < 0.05). CONCLUSION: Compression therapy can effectively reduce the incidence of CIPN, as well as improve the level of anxiety, depression, and sleep disorders in chemotherapy patients. Therefore, medical personnel should closely observe the physical and psychological changes in patients undergoing chemotherapy and provide corresponding preventive measures. REGISTRATION NUMBER: RMYY-LLKS-2022-054. DATE OF REGISTRATION: September 25, 2022.

UBAP2L ensures homeostasis of nuclear pore complexes at the intact nuclear envelope.

Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a role of ubiquitin-associated protein 2-like (UBAP2L) in the assembly and stability of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells. UBAP2L localizes to the nuclear pores and facilitates the formation of the Y-complex, an essential scaffold component of the NPC, and its localization to the NE. UBAP2L promotes the interaction of the Y-complex with POM121 and Nup153, the critical upstream factors in a well-defined sequential order of Nups assembly onto NE during interphase. Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1) to the NE and its interaction with the Y-complex are likewise dependent on UBAP2L. Thus, this NPC biogenesis mechanism integrates the cytoplasmic and the nuclear NPC assembly signals and ensures efficient nuclear transport, adaptation to nutrient stress, and cellular proliferative capacity, highlighting the importance of NPC homeostasis at the intact NE.

KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation.

Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin-associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, develop autoinflammation triggered by nonantigenic cues such as from the environment. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowered the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increased NLRP3-dependent inflammation. Myeloid-specific deletion of PIEZO1/2 protected mice from gouty arthritis. Mechanistically, activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux and promotes NLRP3 inflammasome activation. Activation of PIEZO signaling was sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Last, pharmacological inhibition of KCNN4 alleviated autoinflammation in cells of patients with CAPS and in mice bearing a CAPS mutation. Thus, PIEZO-dependent mechanical inputs boost inflammation in NLRP3-dependent diseases, including CAPS.

Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.