Tumor Cell-Targeting and Tumor Microenvironment-Responsive Nanoplatforms for the Multimodal Imaging-Guided Photodynamic/Photothermal/Chemodynamic Treatment of Cervical Cancer.

Purpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer. Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)-modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects. Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility. Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.

Computed tomography radiomics in predicting patient satisfaction after robotic-assisted total knee arthroplasty.

PURPOSE: After robotic-assisted total knee arthroplasty (RA-TKA) surgery, some patients still experience joint discomfort. We aimed to establish an effective machine learning model that integrates radiomic features extracted from computed tomography (CT) scans and relevant clinical information to predict patient satisfaction three months postoperatively following RA-TKA. MATERIALS AND METHODS: After careful selection, data from 142 patients were randomly divided into a training set (n = 99) and a test set (n = 43), approximately in a 7:3 ratio. A total of 1329 radiomic features were extracted from the regions of interest delineated in CT scans. The features were standardized using normalization algorithms, and the least absolute shrinkage and selection operator regression model was employed to select radiomic features with ICC > 0.75 and P < 0.05, generating the Rad-score as feature markers. Univariate and multivariate logistic regression was then used to screen clinical information (age, body mass index, operation time, gender, surgical side, comorbidities, preoperative KSS score, preoperative range of motion (ROM), preoperative and postoperative HKA angle, preoperative and postoperative VAS score) as potential predictive factors. The satisfaction scale ≥ 20 indicates patient satisfaction. Finally, three prediction models were established, focusing on radiomic features, clinical features, and their fusion. Model performance was evaluated using Receiver Operating Characteristic curves and decision curve analysis. RESULTS: In the training set, the area under the curve (AUC) of the clinical model was 0.793 (95% CI 0.681-0.906), the radiomic model was 0.854 (95% CI 0.743-0.964), and the combined radiomic-clinical model was 0.899 (95% CI 0.804-0.995). In the test set, the AUC of the clinical model was 0.908 (95% CI 0.814-1.000), the radiomic model was 0.709 (95% CI 0.541-0.878), and the combined radiomic-clinical model was 0.928 (95% CI 0.842-1.000). The AUC of the radiomic-clinical model was significantly higher than the other two models. The decision curve analysis indicated its clinical application value. CONCLUSION: We developed a radiomic-based nomogram model using CT imaging to predict the satisfaction of RA-TKA patients at 3 months postoperatively. This model integrated clinical and radiomic features and demonstrated good predictive performance and excellent clinical application potential.

Corrigendum: Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head.

[This corrects the article DOI: 10.3389/fimmu.2023.1340446.].

Neuroticism personality, social contact, and dementia risk: A prospective cohort study.

BACKGROUND: Personality traits, especially neuroticism, can influence susceptibility to dementia. Social contact mitigates stress and risk of dementia, the extent to which social contact can mitigate excess risk associated with neuroticism remains unclear. We aim to investigate whether active social contact is associated with lower neuroticism-associated excess risk of dementia. METHODS: This prospective cohort study examined 393,939 UK Biobank participants (mean [SD] age: 56.4 [8.1] years; 53.7 % female) assessed from 2006 to 2010 and followed up until December 2022. Neuroticism was measured using the Revised Eysenck Personality Questionnaire. Social contact levels were assessed based on household size, contact with family or friends, and group participation. Dementia was determined using linked electronic health records. RESULTS: High neuroticism was associated with increased all-cause dementia risk and cause-specific dementia. Among high neuroticism participants, excess risk of all-cause dementia showed a stepwise decrease with increasing social contact (low: hazard ratios (HR) = 1.27, 95 % confidence interval (CI) = 1.15-1.40; intermediate: HR = 1.20, 95 % CI = 1.12-1.28; high: HR = 1.07, 95 % CI = 1.00-1.15). High social contact similarly decreased excess risk of cause-specific dementia, comparable to those with low neuroticism. LIMITATIONS: Neuroticism and social contact information relied on self-report questionnaires at baseline, with a potential temporal relationship between these factors. CONCLUSION: Active social contact is associated with a stepwise reduction in excess dementia risk and potentially eliminate excess risk of dementia with high neuroticism individuals, supporting social contact as a preventive strategy to attenuate excess risks of dementia from neuroticism personality trait.

Efficient Homojunction/Heterojunction Photocatalyst via Integrating CsPbBr3 Quantum Dot Homojunction with TiO2 for Degradation of Organic Dyes.

A novel TiO2-CsPbBr3(Q) photocatalyst is proposed and rationally constructed, where CsPbBr3 perovskite quantum dots (QDs) of various sizes inside mesopore TiO2 (M-TiO2) are integrated. These perovskite QDs, generated in situ within M-TiO2, establish a type-II homojunction. Interestingly, a Z-scheme heterojunction is simultaneously formed at the interface between CsPbBr3 and TiO2. Due to the coexistence of the type-II homojunction and the Z-scheme heterojunction, photogenerated electrons are effectively transferred from TiO2 to CsPbBr3, thereby suppressing carrier recombination and thus enhancing the degradation of rhodamine B (RhB). Compared with pure CsPbBr3 and TiO2, TiO2-CsPbBr3(Q) shows significantly enhanced photocatalytic performance for RhB degradation. The degradation efficiency of RhB in the presence of the TiO2-CsPbBr3(Q) attains 97.7% in 5 min under light illumination, representing the highest efficiency observed among photocatalysts based on TiO2. This study will facilitate the development of superior semiconductor catalysts for photocatalytic applications.

A convolutional neural network prediction model for aviation nitrogen oxides emissions throughout all flight phases.

In recent years, there has been an increasing amount of research on nitrogen oxides (NOx) emissions, and the environmental impact of aviation NOx emissions at cruising altitudes has received widespread attention. NOx may play a crucial role in altering the composition of the atmosphere, particularly regarding ozone formation in the upper troposphere. At present, the ground emission database based on the landing and takeoff (LTO) cycle is more comprehensive, while high-altitude emission data is scarce due to the prohibitively high cost and the inevitable measurement uncertainty associated with in-flight sampling. Therefore, it is necessary to establish a comprehensive NOx emission database for the entire flight envelope, encompassing both ground and cruise phases. This will enable a thorough assessment of the impact of aviation NOx emissions on climate and air quality. In this study, a prediction model has been developed via convolutional neural network (CNN) technology. This model can predict the ground and cruise NOx emission index for turbofan engines and mixed turbofan engines fueled by either conventional aviation kerosene or sustainable aviation fuels (SAFs). The model utilizes data from the engine emission database (EEDB) released by the International Civil Aviation Organization (ICAO) and results obtained from several in-situ emission measurements conducted during ground and cruise phases. The model has been validated by comparing measured and predicted data, and the results demonstrate its high prediction accuracy for both the ground (R2 > 0.95) and cruise phases (R2 > 0.9). This surpasses traditional prediction models that rely on fuel flow rate, such as the Boeing Fuel Flow Method 2 (BFFM2). Furthermore, the model can predict NOx emissions from aircrafts burning SAFs with satisfactory accuracy, facilitating the development of a more complete and accurate aviation NOx emission inventory, which can serve as a basis for aviation environmental and climatic research. SYNOPSIS: The utilization of the ANOEPM-CNN offers a foundation for establishing more precise emission inventories, thereby reducing inaccuracies in assessing the impact of aviation NOx emissions on climate and air quality.

A Novel growth guidance system for early onset scoliosis: a preliminary in vitro study.

PURPOSE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. METHOD: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001). CONCLUSION: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.

Increased GABA signaling in liver macrophage promotes HBV replication in HBV-carrier mice.

Gamma-aminobutyric acid (GABA) signals in various non-neuronal cells including hepatocytes and some immune cells. Studies, including ours, show that type A GABA receptors (GABAARs)-mediated signaling occurs in macrophages regulating tissue-specific functions. Our recent study reveals that activation of GABAARs in liver macrophages promotes their M2-like polarization and increases HBV replication in mice. This short article briefly summarizes the GABA signaling system in macrophages and discusses potential mechanisms by which GABA signaling promotes HBV replication.

Can the Sterilization Protocol Be Improved to Enhance the Healing of Allograft Tendons? An In Vivo Study in Rabbit Tendons.

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm 2 versus 256 ± 43 /mm 2 , mean difference 188 /mm 2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m 2 versus 8 ± 4 kJ/m 2 , mean difference 8 kJ/m 2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.

Methods comparison of two-dimensional gel electrophoresis for host cell protein characterization.

Two-dimensional electrophoresis (2DE) is a gel-based protein separation method based on size and charge which is commonly used for the characterization of host cell proteins (HCPs) during drug development in biotech and pharmaceutical companies. HCPs are a heterogenous mixture of proteins produced by host cells during a biologics drug manufacturing process. Different gel electrophoresis methods including traditional 2D SDS-PAGE with silver and SYPRO Ruby fluorescent dye staining as well as two-dimensional difference gel electrophoresis (2D-DIGE) were compared for their relative abilities to characterize HCPs. SYPRO Ruby was shown to be more sensitive than silver stain in the traditional 2D gels both with and without product protein present. Silver stain also displayed a significant preference for staining acidic proteins over basic ones while SYPRO Ruby was more consistent in imaging proteins across different isoelectric points. The non-traditional method of 2D-DIGE provides high resolution and reproducibility when comparing samples with similar protein profiles but was limited in imaging HCP spots due to its narrow dynamic range. Overall, 2DE is a powerful tool to separate and characterize HCPs and is optimized by choosing the best stain or method for each specific application. Using a combination of two or more different 2DE staining methods, when possible, provides the most comprehensive coverage to support the characterization of a complex mixture like HCPs. However, in instances where only one staining method can be used, SYPRO Ruby is shown to be the more reliable, more sensitive, and easier to use traditional staining method for most HCP-based applications.

Silver nanoparticles induce iron accumulation-associated cognitive impairment via modulating neuronal ferroptosis.

Silver nanoparticles (AgNPs) are widely used in daily life and medical fields owing to their unique physicochemical properties. Daily exposure to AgNPs has become a great concern regarding their potential toxicity to human beings, especially to the central nervous system. Ferroptosis, a newly recognized programmed cell death, was recently reported to be associated with the neurodegenerative process. However, whether and how ferroptosis contributes to AgNPs-induced neurotoxicity remain unclear. In this study, we investigated the role of ferroptosis in neurotoxic effects induced by AgNPs using in vitro and in vivo models. Our results showed that AgNPs induced a notable dose-dependent cytotoxic effect on HT-22 cells and cognitive impairment in mice as indicated by a decline in learning and memory and brain tissue injuries. These findings were accompanied by iron overload caused by the disruption of the iron transport system and activation of NCOA4-mediated autophagic degradation of ferritin. The excessive free iron subsequently induced GSH depletion, loss of GPX and SOD activities, differential expression of Nrf2 signaling pathway elements, down-regulation of GPX4 protein and production of lipid peroxides, initiating ferroptosis cascades. The mitigating effects of ferrostatin-1 and deferoxamine on iron overload, redox imbalance, neuronal cell death, impairment of mice learning and memory, Aß deposition and synaptic plasticity reduction suggested ferroptosis as a potential molecular mechanism in AgNPs-induced neurotoxicity. Taken together, these results demonstrated that AgNPs induced neuronal cell death and cognitive impairment with Aß deposition and reduction of synaptic plasticity, which were mediated by ferroptosis caused by iron-mediated lipid peroxidation. Our study provides new insights into the underlying mechanisms of AgNPs-induced neurotoxicity and predicts potential preventive strategies.

High-Efficiency Blue-Emitting Mn-Ligand passivated CsPbBr3 nanoplatelets.

Perovskite nanoplatelets (NPLs), as a promising material to achieve pure blue emission, have attracted significant attention in high gamut displays. However, the high surface-to-volume ratio and the loosely connected ligands of NPLs make them susceptible to degradation from light, air and heat. As a result, NPLs often exhibit low photoluminescence (PL) intensity and instability. Here, an Mn-ligand passivation strategy is proposed, in which Mn-doped DMAPbBr3 is used as a precursor. During the perovskite transformation, Mn2+ ions migrate from the lattice of DMAPbBr3 to the surface of CsPbBr3 NPLs, which have strong binding forces with ligands. The final products Mn-CsPbBr3 (M-CPB) NPLs are then acquired by the ligand-induced ripening growth process, which not only exhibit pure blue emission with narrow full width at half maximum (FWHM), but also possess near-unity PL quantum yields (QYs). Besides, M-CPB NPLs show excellent stability due to the strong Mn-ligand passivation layer. Based on the new growth mechanism discovery, the reaction time can be shortened to several minutes by heating. The innovative growth model proposed in this work will provide a paradigm for designing and optimizing future synthesis schemes.

Optimal time window for initiating cefuroxime surgical antimicrobial prophylaxis in spinal fusion surgery: a nested case-control study.

BACKGROUND CONTEXT: Surgical site infections (SSI) are one of the common complications following spinal fusion surgery. Unfortunately, several studies had shown conflicting results regarding optimal timing of surgical antimicrobial prophylaxis (SAP) administration. Due to limitations in population homogeneity and sample size, these studies have not provided significant statistical correlations or clear practical recommendations. PURPOSE: The purpose of the study was to investigate the impact of timing of cefuroxime SAP on the risk of SSI in patients undergoing spinal fusion surgery, and to determine the optimal timing of administration. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: This was a retrospective nested case-control study. All consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021 formed a retrospective cohort. For each SSI case, 2 controls free of SSI at the time of the index date of their corresponding case were selected, matched by age, sex, and calendar year. Electronic record and radiographic data were reviewed retrospectively in electronic database. SAP related data included timing of administration, preoperative dose, intraoperative second dose, and postoperative use. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Subsequently, subgroup analyses were conducted to assess the robustness of the statistical associations. RESULTS: According to the preplanned statistical scheme and matching factors, we matched 236 controls for these SSI cases, and the subsequent statistical analysis was performed on these 354 patients. After adjusting for confounding factors, the results indicated that the risk of SSI was 70% higher in the group receiving SAP 31 to 60 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=1.732, 95%CI 1.031-2.910, p=.038). Additionally, the risk of SSI was 150% higher in the group receiving SAP 61 to 120 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=2.532, 95%CI 1.250-5.128, p=.010). In subgroup analysis, this statistical trend persisted for both deformity surgeries and different SSI classifications. CONCLUSION: Administering cefuroxime SAP within 30 minutes before skin incision significantly reduces the risk of SSI, whether they are deep or superficial, in spinal fusion surgery. This pattern remains consistent among spinal deformity patients.

Exploring the therapeutic potential of isoorientin in the treatment of osteoporosis: a study using network pharmacology and experimental validation.

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.

Early mobilization can reduce the incidence of surgical site infections in patients undergoing spinal fusion surgery: A nested case-control study.

BACKGROUND: To examine the influence of early mobilization on the risk of surgical site infections (SSI) in patients undergoing spinal fusion surgery. METHODS: The retrospective cohort consisted of all consecutive patients who underwent spinal fusion surgery at our institution. For each case of SSI, 2 control patients without SSI at the corresponding index date were selected. Mobilization was predefined as "delayed" if it occurred more than 36 hours postoperatively. To account for potential confounding variables, we performed further adjustments using conditional logistic regression models. Subgroup analyses were conducted to evaluate the robustness of the statistical associations. RESULTS: Following the predefined statistical protocol and matching criteria, we matched 236 control cases to the SSI cases. Upon adjustment for confounding factors, our findings revealed that the risk of SSI was 120% higher in the group beginning mobilization more than 36 hours after surgery compared to the group beginning mobilization within 36 hours postoperatively (odds ratio = 2.206, 95% confidence interval 1.169-4.166, P = .015). In subgroup analyses, this statistical trend remained consistent. CONCLUSIONS: Early mobilization within 36 hours following spinal fusion surgery significantly reduces the risk of SSI. This pattern of reduced risk remains consistent among patients with degenerative diseases or spinal deformities.

Interference Morphology of Free-Growing Tendrils and Application of Self-Locking Structures.

Organisms can adapt to various complex environments by obtaining optimal morphologies. Plant tendrils evolve an extraordinary and stable spiral morphology in the free-growing stage. By combining apical and asymmetrical growth strategies, the tendrils can adjust their morphology to wrap around and grab different supports. This phenomenon of changing tendril morphology through the movement of growth inspires a thoughtful consideration of the laws of growth that underlie it. In this study, tendril growth is modeled based on the Kirchhoff rod theory to obtain the exact morphological equations. Based on this, the movement patterns of the tendrils are investigated under different growth strategies. It is shown that the self-interference phenomenon appears as the tendril grows, allowing it to hold onto its support more firmly. In addition, a finite element model is constructed using continuum media mechanics and following the finite growth theory to simulate tendril growth. The growth morphology and self-interference phenomenon of tendrils are observed visually. Furthermore, an innovative class of fluid elastic actuators is designed to verify the growth phenomena of tendrils, which can realize the wrapping and locking functions. Several experiments are conducted to measure the end output force and the smallest size that can be clamped, and the output efficiency of the elastic actuator and the optimal working pressure are verified. The results presented in this study could reveal the formation law of free tendril spiral morphology and provide an inspiring idea for the programmability and motion control of bionic soft robots, with promising applications in the fields of underwater rescue and underwater picking.

Highly efficient and stable Cs3Mn0.93Zn0.07Br5@SiO2 for wide color gamut backlight displays.

Mn-based perovskites have become a new candidate material for backlight display applications. However, low efficiency and poor stability are the key problems limiting the application of Mn-based perovskites. In this work, Zn-doped and SiO2-encapsulated Cs3MnBr5, denoted as Cs3Mn0.93Zn0.07Br5@SiO2 (CMZBS), was successfully synthesized to improve the photoluminescence quantum yield (PLQY) and stability. After Zn doping, the PLQY increased from 51% to 72% due to the reduction in the energy transfer between [MnBr4]2-. The PLQY can be further improved to 80% after coating SiO2. Compared with Cs3MnBr5 (CMB), CMZBS showed better stability against thermal, air, light, and polar solvents (ethanol and isopropanol). In addition, a white LED (WLED) device with a CIE of (0.323, 0.325) was fabricated by integrating CMZBS and the red phosphor K2SiF6:Mn4+ on a 465 nm blue GaN chip, which exhibited a high luminous efficiency of 92 lm W-1 and excellent stability, demonstrating its great potential application in wide color gamut displays.

Effect Modification of COVID-19 Symptoms on the Association Between Timing of Surgery and Postoperative Complications in Pediatric Spinal Deformity: A Prospective Cohort Study.

OBJECTIVE: The purpose of this study was to explore the optimal timing and associated risks of pediatric spinal deformity surgery during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: All consecutive surgical cases for spinal deformity between September 2022 and May 2023 were included. The population was divided into several categories according to the time from diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to the day of surgery. Postoperative complications were analyzed using logistic regression, and we simultaneously showed the results from the crude model, minimally adjusted model, and fully adjusted model. RESULTS: A total of 81 consecutive patients were enrolled. In the fully adjusted model, compared with pre-COVID-19 patients, peri-COVID-19 patients had a 4.5-fold increased risk of postoperative complications (odds ratio = 5.5, 95% confidence interval 1.1-27.2, P = 0.037), early post-COVID-19 patients had a 2.3-fold increased risk (odds ratio= 3.3, 95% confidence interval 0.7-16.1, P = 0.133), and late post-COVID-19 patients were at essentially equal risk. In asymptomatic population, early post-COVID-19 patients and late post-COVID-19 patients appeared to be at equal risk compared with pre-COVID-19 patients. For patients with persistent symptoms, is necessary to wait at least 8 weeks or even longer after SARS-CoV-2 infection. Interaction tests demonstrated that the effect of the timing of surgery on postoperative complications significantly differed in populations with different symptoms. CONCLUSIONS: Surgery for pediatric spinal deformity should be postponed until 8 weeks after SARS-CoV-2 infection in cases with COVID-19-related symptoms within 2 weeks prior to surgery; whereas, for those who are asymptomatic within 2 weeks prior to surgery, an interval of 4 weeks seemed to be sufficient.

Metabolic reprogramming driven by METTL1-mediated tRNA m7G modification promotes acquired anlotinib resistance in oral squamous cell carcinoma.

Tyrosine kinase inhibitors (TKIs) are frequently utilized in the management of malignant tumors. Studies have indicated that anlotinib has a significant inhibitory effect on oral squamous cell carcinoma (OSCC). However, the mechanisms underlying the development of resistance with long-term anlotinib treatment remain obscure. Our research found that METTL1 expression was heightened in anlotinib-resistant OSCC cells. We observed that METTL1 played a role in fostering resistance to anlotinib in both transgenic mouse models and in vitro. Mechanistically, the elevated METTL1 levels in anlotinib-resistant OSCC cells contributed to enhanced global mRNA translation and stimulated oxidative phosphorylation (OXPHOS) through m7G tRNA modification. Bioenergetic profiling demonstrated that METTL1 drived a metabolic shift from glycolysis to OXPHOS in anlotinib-resistant OSCC cells. Additionally, inhibition of OXPHOS biochemically negated METTL1's impact on anlotinib resistance. Overall, this study underscores the pivotal role of METTL1-mediated m7G tRNA modification in anlotinib resistance and lays the groundwork for novel therapeutic interventions to counteract resistance in OSCC.

Myeloid zinc finger 1 knockdown promotes osteoclastogenesis and bone loss in part by regulating RANKL-induced ferroptosis of osteoclasts through Nrf2/GPX4 signaling pathway.

The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. MZF1, belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by micro-computed tomography and histological staining. Our findings indicate that MZF1-/- mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene-editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1-/- and wild-type cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin fluorescence results showed that the MZF1-/- group produced more tartrate-resistant acid phosphatase-positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including tartrate-resistant acid phosphatase, CTSK, c-Fos, and NFATc1) was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot. The expression of key genes of osteoclast differentiation in the MZF1-/- group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1-/- group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.