Biomechanical Effects of Multi-segment Fixation on Lumbar Spine and Sacroiliac Joints: A Finite Element Analysis.

OBJECTIVE: Spine fixation surgery affects the biomechanical environment in the sacroiliac joint (SIJ), which may lead to the SIJ pain or degeneration after surgery. The purpose of this study is to determine the impact of the number and position of fixed segments on the SIJs and provide references for surgeons to plan fixation levels and enhance surgical outcomes. METHODS: The intact lumbar-pelvis finite element (FE) models and 11 fixation FE models with different number and position of fixed segments were developed based on CT images. A 400N follower load and 10° range of motion (ROM) of the spine were applied to the superior endplate of L1 to simulate the flexion, extension, bending and torsion motion after surgery. The peak stress on the SIJs, lumbar intervertebral discs, screws and rods were calculated to evaluate the biomechanical effects of fixation procedures. RESULTS: With the lowermost instrumented vertebra (LIV) of L5 or S1, the peak stress on SIJs increased with the number of fixed segments increasing. The flexion motion led to the greater von Mises stress on SIJ compared with other load conditions. Compared with the intact model, peak stress on all fixed intervertebral discs was reduced in the models with less than three fixed segments, and it increased in the models with more than three fixed segments. The stress on the SIJ was extremely high in the models with all segments from L1 to L5 fixed, including L1-L5, L1-S1 and L1-S2 fixation models. The stress on the segment adjacent to the fixed segments was significant higher compared to that in the intact model. The peak stress on rods and screws also increased with the number of fixed segments increasing in the flexion, extension and bending motion, and the bending and flexion motions led to the greater von Mises stress on SIJs. CONCLUSION: Short-term fixation (≤2 segments) did not increase the stress on the SIJs significantly, while long-term segment fixation (≥4 segments) led to greater stress on the SIJs especially when all the L1-L5 segments were fixed. Unfixed lumbar segments compensated the ROM loss of the fixed segments, and the preservation of lumbar spine mobility would reduce the risks of SIJ degeneration.

Epidemiological characteristics of traumatic spinal fractures among the elderly in China.

The exploration of traumatic spinal fractures (TSFs) within the senior demographic has not been thoroughly scrutinized, particularly with respect to variations across genders, age groups, seasonal periods, and causative factors. This retrospective analysis aimed to dissect differences in the prevalence and characteristics of TSFs among the elderly, factoring in gender, age, seasonal timing, and causation. A retrospective analysis was conducted on the medical and imaging records of 1,415 patients, all aged 60 years or older, who were diagnosed with TSFs from 2013 to 2019. This study categorized the data by gender, age groups (60-70, 70-80, and 80 years or older), seasons, and the cause of injuries, including road traffic crashes (RTCs), falls from low heights (LHF), falls from high heights (HHF), and injuries incurred during everyday activities and agricultural labor (DFI). Male patients exhibited notably higher incidences of RTCs, high-height falls (HHFs), outdoor incidents, comas post-injury, fractures of the lower limbs (LLFs), pelvic fractures (PFs), rib fractures (RFs), intra-thoracic injuries (ITIs), intra-abdominal injuries (IAIs), cervical fractures, and spinal cord injuries (SCIs). With advancing age, there was a marked decline in occurrences of RTCs, HHFs, outdoor incidents, RFs, craniocerebral injuries (CCIs), ITIs, cervical fractures, and SCIs, while the incidences of DFIs, indoor incidents, and thoracic and lumbar (T + L) fractures notably increased. During autumn, LLF occurrences were significantly reduced, whereas the winter season saw an increase in thoracic fractures. Spring time was associated with a higher frequency of lumbar fractures and noncontiguous spinal fractures (NSFs). Significant distinctions were observed in the age distribution, injury circumstances, associated injuries, and SCIs between high-energy impacts (RTCs and HHFs) and low-energy traumas (LHFs and DFIs). In the elderly demographic, TSFs exhibited discernible distinctions based on gender, age, seasonal variations, and etiological factors, impacting the nature and circumstances of injuries, associated traumas, complications, fracture sites, and the occurrence of SCIs.

A novel chlorin derivative Shengtaibufen (STBF) mediated photodynamic therapy combined with iodophor for the treatment of chronic superficial leg wounds infected with methicillin-resistant Staphylococcus aureus: A retrospective clinical study.

OBJECTIVE: Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. PATIENTS AND METHODS: This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. RESULTS: We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 107±2.13 × 107 to 6.49 × 107±2.01 × 107 CFU/cm2, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life). CONCLUSION: Our data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.

Germline loss in C. elegans enhances longevity by disrupting adhesion between niche and stem cells.

Ageing and fertility are intertwined. Germline loss extends the lifespan in various organisms, termed gonadal longevity. However, the original longevity signal from the somatic gonad remains poorly understood. Here, we focused on the interaction between germline stem cells (GSCs) and their niche, the distal tip cells (DTCs), to explore the barely known longevity signal from the somatic gonad in C. elegans. We found that removing germline disrupts the cell adhesions between GSC and DTC, causing a significant transcriptomic change in DTC through hmp-2/ß-catenin and two GATA transcription factors, elt-3 and pqm-1 in this niche cell. Inhibiting elt-3 and pqm-1 in DTC suppresses gonadal longevity. Moreover, we further identified the TGF-ß ligand, tig-2, as the cytokine from DTC upon the loss of germline, which evokes the downstream gonadal longevity signalling throughout the body. Our findings thus reveal the source of the longevity signalling in response to germline removal, highlighting the stem cell niche as a critical signalling hub in ageing.

Lung decellularized matrix-derived 3D spheroids: Exploring silicosis through the impact of the Nrf2/Bax pathway on myofibroblast dynamics.

Silicosis is an occupational respiratory disease caused by long-term inhalation of high concentrations of free silica particles. Studies suggest that oxidative stress is a crucial initiator of silicosis fibrosis, and previous studies have linked the antioxidative stress transcription factor known as Nrf2 to fibrosis antagonism. Myofibroblasts play a pivotal role in tissue damage repair due to oxidative stress. Unlike physiological repair, myofibroblasts in fibrosis exhibit an apoptosis-resistant phenotype, continuously synthesising and secreting significant amounts of collagen and other extracellular matrices, which could be a direct cause of silicosis fibrosis. However, the relationship and mechanism of action between oxidative stress and myofibroblast apoptosis resistance remain unclear. In this study, a new 3D cell culture model using mice lung decellularised matrix particles and fibroblasts was developed, simulating the changes in myofibroblasts during the development of silicotic nodules. Western Blot results indicate that silica stimulation leads to increased collagen deposition and decreased apoptosis-related protein Bax and oxidative stress-related protein Nrf2 in the 3D spheroid model. Immunofluorescence experiments reveal co-localisation in their expression. In Nrf2 overexpressing spheroids, Bax exhibits significant upregulation. In the Nrf2 knockout spheroids, Bax is also significantly downregulated; after intervention with Bax inhibitors, a significant downregulation of Bax-induced apoptosis was also detected in the Nrf2-overexpressed spheroids. In contrast, Bax-induced apoptosis showed a significant upregulation trend in Nrf2-overexpressed spheroids after intervention with Bax agonists. The results demonstrate that the spheroid model can mimic the development process of silicotic nodules, and silica stimulation leads to an apoptosis-resistant phenotype in myofibroblasts in the model, acting through the Nrf2/Bax pathway. This research establishes a new methodology for silicosis study, identifies therapeutic targets for silicosis, and opens new avenues for studying the mechanisms of silicosis fibrosis.

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Dietary patterns suggest that dark chocolate intake may have an inhibitory effect on oral cancer: a Mendelian randomization study.

Background: Previous studies reported that variations in dietary intake patterns substantially impact human health, specifically tumorigenesis. However, confounding factors in previous cohort studies have obscured the relationship between dietary differences and the risk of oral cancer (OC). Materials and methods: We developed an outcome dataset from genome-wide association studies (GWAS) data on three OCs within the GAME-ON project, using GWAS-META merging. We extracted 21 dietary exposures, including 10 dietary patterns, 6 vitamins, and 5 micronutrients, from the UK Biobank database, using the inverse variance weighting method as the primary statistical method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. Serum metabolite concentrations were adjusted using multivariate Mendelian randomization. Results: Of the 10 analyzed dietary patterns, 8 showed no significant association with the risk of developing OC. Consumption of dark chocolate (inverse variance weighted [IVW]: Odds ratio (OR) = 0.786, 95% confidence interval [CI]: 0.622-0.993, p = 0.044) and sweet pepper exhibited an inverse relationship with OC risk (IVW: OR = 0.757, 95% CI: 0.574-0.997, p = 0.048). Reverse MR analysis revealed no reverse causality. Furthermore, no significant correlation was observed between the intake of 6 vitamins and 5 micronutrients and the risk of developing OC. After using multivariable MR to adjust for serum caffeine, linoleate, theophylline, and theobromine metabolism levels, consuming dark chocolate was unrelated to a decreased risk of OC. After adjusting each serum metabolite individually, the observed p-values deviated from the original values to varying degrees, indicating that the components of dark chocolate could have different effects. Among these components, theophylline demonstrated the most significant inhibitory effect. Conclusion: This study demonstrated a causal relationship between the intake of dark chocolate and sweet peppers and a lower risk of OC. The components of dark chocolate could have different effects.

Exploring the Relationship Between Subcutaneous Fat Index and Neck Pain in Patients with Spinal Cervical Spondylosis: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: This study measures the subcutaneous fat index (SFI) of the cervical spine in patients with spinal cervical spondylosis using cervical magnetic resonance imaging and explores its relationship with neck pain in patients with spinal cervical spondylosis. METHODS: In this single-center retrospective study, 298 patients hospitalized for spinal cervical spondylosis between January and June 2021 were initially considered. After applying inclusion and exclusion criteria, 93 patients were enrolled. The cervical magnetic resonance imaging data for these patients were analyzed using A-Site software. The SFI was measured at the median sagittal plane on T2-weighted images. Patients were categorized into 2 groups based on their admission complaints: those with cervical pain and those without it. Differences between these groups were then statistically analyzed. RESULTS: The mean SFIs with standard deviations for the neck and non-neck pain groups were 36.4% ± 7.7% and 27.0% ± 7.9%, respectively, with a significant difference (P < 0.0001). The SFI was consistently higher across all neck segments in the neck pain group compared to the nonneck pain group (P < 0.05). The 2 groups had no statistically significant difference in the body mass index. CONCLUSIONS: The SFI provides a more precise assessment of muscle and fat distribution in the posterior cervical region than body mass index and is generally higher in patients with spinal cervical spondylosis who experience neck pain. These findings suggest the importance of early functional exercises postsurgery for potentially improving surgical outcomes in this patient population.

The land of homesickness: The impact of homesteads on the social integration of rural migrants.

Promoting the social integration of rural migrants is key to improving the mechanism of rural-urban integration and development. This study utilizes the 2017 China Migrants Dynamic Survey and matched urban macro data to systematically explore the impact of homesteads on the social integration of rural migrants. Research has shown that social integration of rural migrants will be inhibited if they own homesteads. Simultaneously, the degree of inhibition varies according to the individual characteristics of rural migrants, the region to which they belong, and other factors. Specifically, when rural migrants aged 18 to 50 own homesteads, their degree of social integration into the cities they move into will be low. At the same time, for rural migrants in the central region, homestead ownership will not affect their degree of social integration. In addition, the mechanism analysis shows that increased housing expenditure inhibits rural migrants' willingness to integrate. Meanwhile, owning contracted land and owning a house in the city also affect the degree of social integration of rural migrants to a certain extent. The findings of this study can broaden research on the effects of land on the free movement of population factors. In the meantime, it provides theoretical references for improving the level of social integration of migrants, enhancing people's well-being, and improving the mechanism of urban-rural integration and development.

Efficient Quasi-2D Perovskite Based Blue Light-Emitting Diodes with Carbon Dots Modified Hole Transport Layer.

Quasi-2D perovskites based blue light-emitting diodes (LEDs) suffer from its poor electroluminescence performance, mainly caused by the nonradiative recombination in in defect-rich low-n phases and the unbalanced hole-electron injection in the device. Here, we developed a highly efficient quasi-2D perovskite based sky-blue LEDs behaving recorded external quantum efficiency (EQE) of 21.07% by employing carbon dots (CDs) as additives in the hole transport layer (HTL). We ascribe the high EQE to the effective engineering of CDs: (1) The CDs at the interface of HTLs can suppress the formation of low-efficient n = 1 phase, resulting a high luminescence quantum yield and energy transfer efficiency of the mixed n-phase quasi-2D perovskites. (2) The CDs additives can reduce the conductivity of HTL, partially blocking the hole injection, and thus making more balanced hole-electron injection. The CDs-treated devices have excellent Spectral stability and enhanced operational stability and could be a new alternative additive in the perovskite optoelectronic devices.

Underlying Mechanism of Fluoride Inhibits Colonic Gland Cells Proliferation by Inducing an Inflammation Response.

The integrity of colonic gland cells is a prerequisite for normal colonic function and maintenance. To evaluate the underlying injury mechanisms in colonic gland cells induced by excessive fluoride (F), forty-eight female Kunming mice were randomly allocated into four groups and treated with different concentrations of NaF (0, 25, 50, and 100 mg F-/L) for 70 days. As a result, the integrity of the colonic mucosa and the cell layer was seriously damaged after F treatment, as manifested by atrophy of the colonic glands, colonic cell surface collapse, breakage of microvilli, and mitochondrial vacuolization. Alcian blue and periodic acid Schiff staining revealed that F decreased the number of goblet cells and glycoprotein secretion. Furthermore, F increased the protein expression of TLR4, NF-κB, and ERK1/2 and decreased IL-6, interfered with NF-κB signaling, following induced colonic gland cells inflammation. The accumulation of F inhibited proliferation via the JAK/STAT signaling pathway, as characterized by decreased mRNA and protein expression of JAK, STAT3, STAT5, PCNA, and Ki67 in colon tissue. Additionally, the expression of CDK4 was up-regulated by increased F concentration. In conclusion, excessive F triggered colonic inflammation and inhibited colonic gland cell proliferation via regulation of the NF-κB and JAK/STAT signaling pathways, leading to histopathology and barrier damage in the colon. The results explain the damaging effect of the F-induced inflammatory response on the colon from the perspective of cell proliferation and provide a new idea for explaining the potential mechanism of F-induced intestinal damage.

Investigation on the contaminate of hand washing activities on the surface of environmental objects in intensive care unit.

To detect the contaminate of faucets in hospitals and the splash during hand washing, and to explore the reasonable layout of hand washing pools. Two faucets with roughly the same spatial layout in the ICU of a third-class first-class general hospital were selected, and the farthest splashing distance and specific splashing points were measured by color paper. Samples were detected by ATP detection technology and routine microbial detection method, and the contaminate of faucets was analyzed. After 72 h of daily hand-washing activities, the furthest distance to the splash point was about 100 cm around the faucet, and the place 40-110 cm around the faucet was contaminated seriously. The farthest distance that the splash point reached was about 80 cm around the faucet with the center of the circle, and the area 40-60 cm around the faucet was heavily contaminated. The distance from the water outlet of the long handle and the short handle faucet to the detection point had a high negative correlation (r = - 0.811, P < 0.001) and a moderate negative correlation (r = - 0.475, P = 0.001) with the number of splash points, respectively. The qualified rates of ATP detection and microbial culture were 25% and 15%, respectively. Pseudomonas aeruginosa, Staphylococcus epidermidis, and other pathogenic bacteria were detected in the water outlet of the faucet and the surrounding environment. Safe hand hygiene facilities are one of the important guarantees of hand hygiene effect. Clean objects and objects related to patients should not be placed within 1 m range near the water outlet of faucet. Anti-splash baffle should be installed as much as possible when conditions permit to reduce the contaminate caused by splash during hand washing.

Baicalein attenuates oxidative damage in mice haematopoietic cells through regulation of PDGFRß.

Platelet-derived growth factor receptor ß (PDGFRß) plays a crucial role in murine haematopoiesis. Baicalein (BAI), a naturally occurring flavonoid, can alleviate disease damage through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms. However, whether BAI attenuates oxidative damage in murine haematopoietic cells by PDGFRß remains unexplored. In this study, we utilized a tert-butyl hydroperoxide (TBHP)-induced BaF3 cell injury model and an ionising radiation (IR)-induced mice injury model to investigate the impact of the presence or absence of PDGFRß on the pharmacological effects of BAI. In addition, the BAI-PDGFRß interaction was characterized by molecular docking and dynamics simulations. The results show that a specific concentration of BAI led to increased cell viability, reduced reactive oxygen species (ROS) content, upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression, and its downstream target genes heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and activated protein kinase B (AKT) pathway in cells expressing PDGFRß plasmid and experiencing damage. Similarly, BAI elevated lineage-Sca1+cKIT+ (LSK) cell proportion, promoted haematopoietic restoration, enhanced NRF2-mediated antioxidant response in PDGFRß+/+ mice. However, despite BAI usage, PDGFRß knockout mice (PDGFRß-/-) showed lower LSK proportion and less antioxidant capacity than the total body irradiation (TBI) group. Furthermore, we demonstrated an interaction between BAI and PDGFRß at the molecular level. Collectively, our results indicate that BAI attenuates oxidative stress injury and helps promote haematopoietic cell recovery through regulation of PDGFRß.

Activation of Wnt/ß-catenin signal induces DCs to differentiate into immune tolerant regDCs in septic mice.

BACKGROUND: Sepsis is a common complication among patients in intensive care units, and has a high mortality rate, with no effective therapies to date. As immunosuppression has become the research focus of sepsis, the regulatory role of dendritic cells (DCs) in the immune response to sepsis has received attention. OBJECTIVE: To investigate the role of the Wnt/ß-catenin signaling pathway in inducing the differentiation of splenic DCs in mice with sepsis caused by cecal ligation and puncture (CLP). METHODS: C57bl/6 mice were randomly divided into three groups, namely the sham, 24 h post-CLP, and 72 h post-CLP groups. Levels of regulatory T cells (Tregs) among splenic mononuclear cells, suppressor T cells (TSs), and surface markers, such as major histocompatibility complex class II (MHC-II), co-stimulatory molecules (CD80 and CD86), negative co-stimulatory molecule death-ligand 1 (PD-L1), CC chemokine receptor-5 (CCR5), and CC chemokine receptor-7 (CCR7), were analyzed via flow cytometry for each group of mice post-surgery. CD11c+ DCs were purified from the splenic mononuclear cells of each group, and the expression of ß-catenin, Wnt5a, and Wnt3a was detected using RT-PCR and western blotting.Each group of DCs was incubated with LPS-containing culture solution, and the supernatant of the culture solution was collected after 24 hours to detect the level of Tumor necrosis factor-α(TNF-α), interleukin (IL)-6, IL-12, and IL-10. RESULTS: Compared with that in the sham group, the expression of ß-catenin, Wnt5a, and Wnt3a in splenic DCs of the other two groups of mice increased with prolonged CLP exposure (P<0.05). Meanwhile, the proportion of Tregs and TSs increased in the mouse spleens after CLP, and levels of DC surface molecules, such as CCR5, CCR7, CD80, CD86, and MHC-II, decreased to different degrees, whereas those of PD-L1 increased. These results suggested that DCs differentiate towards regulatory DCs (regDCs) after CLP in mice. The results of ELISA showed that the longer the exposure time after CLP, the lower the ability of DCs to secrete TNF-α and IL-12, but the higher the level of IL-10 and IL-6. CONCLUSION: The Wnt/ß-catenin signaling pathway activates and induces regDCs differentiation in the splenic DCs of mice with sepsis and participates in the regulation of immune tolerance in the organism.

Central role of Sigma-1 receptor in ochratoxin A-induced ferroptosis.

Ochratoxin A (OTA), a secondary fungal metabolite known for its nephrotoxic effects, is prevalent in various feeds and food items. Our recent study suggests that OTA-induced nephrotoxicity is linked to the Sigma-1 receptor (Sig-1R)-mediated mitochondrial pathway apoptosis in human proximal tubule epithelial-originated kidney-2 (HK-2) cells. However, the contribution of Sig-1R to OTA-induced nephrotoxicity involving other forms of regulated cell death, such as ferroptosis, remains unexplored. In this investigation, cell viability, malondialdehyde (MDA) levels, glutathione (GSH) levels, and protein expressions in HK-2 cells treated with OTA and/or Ferrostatin-1/blarcamesine hydrochloride/BD1063 dihydrochloride were assessed. The results indicate that a 24 h-treatment with 1 µM OTA significantly induces ferroptosis by inhibiting Sig-1R, subsequently promoting nuclear receptor coactivator 4 (NCOA4), long-chain fatty acid-CoA ligase 4 (ACSL4), arachidonate 5-lipoxygenase (ALOX5), autophagy protein 5 (ATG5), and ATG7, inhibiting ferritin heavy chain (FTH1), solute carrier family 7 member 11 (SLC7A11/xCT), glutathione peroxidase 4 (GPX4), peroxiredoxin 6 (PRDX6), and ferroptosis suppressor protein 1 (FSP1), reducing GSH levels, and increasing MDA levels (P < 0.05). In conclusion, OTA induces ferroptosis by inhibiting Sig-1R, subsequently promoting ferritinophagy, inhibiting GPX4/FSP1 antioxidant systems, reducing GSH levels, and ultimately increasing lipid peroxidation levels in vitro.

Effect of Otago exercise on fear of falling in older adults: a systematic review and meta-analysis.

BACKGROUND: Approximately 40-70% of older adults who have experienced falls develop fear of falling (FOF), with the incidence rate in nursing home residents reaching as high as 79.4%. An increasing number of studies have focused on the effect of the Otago Exercise Programme (OEP) on reducing FOF among older adults, yet comprehensive analysis is lacking due to regional and demographic variations. Therefore, this study integrates the relevant literature to provide evidence supporting interventions aimed at alleviating FOF among older adults. OBJECTIVE: To evaluate the impact of OEP on FOF in older adults through meta-analysis. METHODS: We searched ten databases using computer systems, covering all records up to May 1, 2024. Two researchers independently conducted the literature screening, bias risk assessment, and data extraction. We performed data analysis using RevMan 5.3 and Stata 15.0 software, assessed result stability through sensitivity analysis, and examined publication bias with funnel plots and Egger's test. RESULTS: Sixteen RCTs were included. Meta-analysis revealed that the OEP significantly reduced FOF among older adults [SMD = 0.96, 95%CI (0.68, 1.23), P < 0.00001]. Subgroup analysis revealed that interventions lasting more than 16 weeks [SMD = 1.12, 95%CI (0.75, 1.49), P < 0.00001], with a frequency of more than twice a week [SMD = 0.99, 95%CI (0.64, 1.35), P < 0.00001], and for older adults in community and nursing institutions [SMD = 1.03, 95%CI (0.50, 1.57), P = 0.0002] were more effective. A comparison of the 16-week and 24-week interventions revealed that the latter had better outcomes [SMD = 0.87, 95%CI (0.66, 1.08), P = 0.0004]. CONCLUSION: Current evidence indicates that OEP effectively reduces FOF among older adults. It is recommended that interventions last for more than 24 weeks, occur more than twice a week, and suitable for application among older adults in community settings or elder care institutions.

Penetrative Ionic Organic Molecular Cage Nanozyme for the Targeted Treatment of Keratomycosis.

Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe2⁺ with carboxyl anions and phenolic hydroxyls in the organic cage, and further deposition of silver nanoparticles on the surface of OMC-Fe complex. The as-prepared OMCzyme demonstrates excellent water dispersion, peroxidase-like activity, in vitro and in vivo biocompatibility, and corneal penetration. Notably, the nanozyme displays targeted antifungal activity, effectively combating Fusarium solani with negligible cytotoxicity toward human corneal epithelial cells. The hybrid mimic is further demonstrated to be effective in treating keratomycosis in mice, indicating the potential of OMCzyme for curing fungal infectious diseases.