Is 3D-printed self-stabilizing endoprosthesis reconstruction without supplemental fixation following total sacrectomy a viable approach for sacral tumours?

PURPOSE: The spinopelvic reconstruction poses significant challenges following total sacrectomy in patients with malignant or aggressive benign bone tumours encompassing the entire sacrum. In this study, we aim to assess the functional outcomes and complications of an integrated 3D-printed sacral endoprostheses featuring a self-stabilizing design, eliminating the requirement for supplemental fixation. METHODS: We retrospectively analyzed patients with sacral tumours who underwent total sacrectomy followed by reconstruction with 3D-printed self-stabilizing endoprosthesis. Clinically, we evaluated functional outcomes using the 1993 version of the musculoskeletal tumour society (MSTS-93) score. Perioperative and postoperative complications were also documented. RESULTS: 10 patients met final inclusion criteria. The median age was 49 years (range, 31-64 years). The median follow-up time was 26.5 months (range, 15-47 months). Median postoperative functional MSTS-93 was 22.5 (range, 13-25). The median operation time was 399.5 min (305-576 min), and the median intraoperative blood loss was and 3200 ml (2400-7800 ml). Complications include wound dehiscence in one patient, bowel, bladder, and sexual dysfunction in four patients, cerebrospinal fluid leak in one patient, and tumour recurrence in one patient. There were no mechanical complications related to the endoprosthesis at the last follow-up. CONCLUSION: The utilization of 3D-printed self-stabilizing endoprosthesis proved to be a viable approach, yielding satisfactory short-term outcomes in patients undergoing total sacral reconstruction without supplemental fixation.

Structure-function coupling reveals the brain hierarchical structure dysfunction in Alzheimer's disease: A multicenter study.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive decline. To date, the specific dysfunction in the brain's hierarchical structure in AD remains unclear. METHODS: We introduced the structural decoupling index (SDI), based on a multi-site data set comprising functional and diffusion-weighted magnetic resonance imaging data from 793 subjects, to assess their brain hierarchy. RESULTS: Compared to normal controls (NCs), individuals with AD exhibited increased SDI within the posterior superior temporal sulcus, insular gyrus, precuneus, hippocampus, amygdala, postcentral gyrus, and cingulate gyrus; meanwhile, the patients with AD demonstrated decreased SDI in the frontal lobe. The SDI in those regions also showed a significant correlation with cognitive ability. Moreover, the SDI was a robust AD neuroimaging biomarker capable of accurately distinguishing diagnostic status (area under the curve [AUC] = 0.86). DISCUSSION: Our findings revealed the dysfunction of the brain's hierarchical structure in AD. Furthermore, the SDI could serve as a promising neuroimaging biomarker for AD. HIGHLIGHTS: This study utilized multi-center, multi-modal data from East Asian populations. We found an increased spatial gradient of the structure decoupling index (SDI) from sensory-motor to higher-order cognitive regions. Changes in SDI are associated with energy metabolism and mitochondria. SDI can identify Alzheimer's disease (AD) and further uncover the disease mechanisms of AD.

Advancements in Photothermal Therapy Using Near-Infrared Light for Bone Tumors.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

Can the digitalization level of agriculture improve its ecological efficiency under carbon constraints: Evidence from China.

The interplay between digitalization and economic development constitutes a pivotal global issue, yet empirical research on agricultural ecological efficiency in developing countries remains limited. This study initially establishes a measurement system and a comprehensive index for the level of agricultural digitalization. Subsequently, it delineates the relationship between agricultural digitalization level and agroecological efficiency using the spatial Durbin model, and ultimately explores the enhancing effect of agricultural digitalization level on agroecological efficiency using China as a case study. Research reveals that the agricultural ecological efficiency across the 31 mainland Chinese provinces demonstrates a generally linear upward trajectory, embodying both agglomeration and heterogeneity. The level of agricultural digitization exerts a significant, positive direct impact and facilitates a spatial spillover effect on agricultural ecological efficiency. Other control variables, such as financial support for agriculture and local economic development, impart a positive direct impact on regional agricultural ecological efficiency, while rural household operating income propels a positive spatial spillover effect on adjacent areas. The findings furnish guidance for developing countries to adeptly execute digital rural construction, aiming to enhance agricultural ecological efficiency amidst carbon constraints.

The evaluation and optimization of the agricultural sustainable development based on a data-driven approach: A case from Northern Anhui.

The sustainable advancement of agriculture stands as the fundamental cornerstone of sustainable human progress. This study introduces a data-centric methodological framework founded upon the holistic delineation of measurement, feature assessment, and pathway enhancement for agricultural sustainability. Initially, the research articulates a comprehensive evaluative schema incorporating sub-dimensions encompassing agricultural production, agricultural economics, the agricultural resource environment, and rural society, grounded in sustainable development theory. Subsequently, it devises a methodological apparatus for assessing and enhancing sustainable development capabilities, employing entropy evaluation methods and exploratory spatial data analysis techniques. Employing North Anhui as a case study, the viability of this approach is substantiated. The empirical inquiry conducted within this article operationalizes comprehensive evaluation and explores pathways for optimizing agricultural sustainability, focusing on the period spanning 2011 to 2020 in Northern Anhui. The findings affirm the feasibility and efficacy of the data-driven approach. Recommendations derived from the empirical exploration of agricultural sustainability pathways at the local level offer valuable insights for governmental authorities and policymakers. This research endeavor could be extrapolated to other geographical locales worldwide, fostering innovative strides in the sustainable development of regional agriculture.

Corrigendum to "The evaluation and optimization of the agricultural sustainable development based on a data-driven approach: A case from Northern Anhui" [Heliyon 10(12) June 2024, Article e32963].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e32963.].

Assessments of Subjective Visual Gravity and Spontaneous Nystagmus in Patients With Vestibular Neuritis.

OBJECTIVE: This study aimed to assess the correlation between the spontaneous nystagmus (SN) and the subjective visual vertical/horizontal (SVV/SVH) among patients with vestibular neuritis (VN) at the different head positions. STUDY DESIGN: Case-control study. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine. METHODS: This study evaluated the SVV/SVH in both healthy subjects and patients with VN. These evaluations were performed in 5 different head positions: upright, 45° tilt to the left, 90° tilt to the left, 45° tilt to the right, and 90° tilt to the right. Additionally, the intensity of SN, as measured by slow-phase velocity, was recorded. RESULTS: In patients with VN, a significant correlation was observed between SN and SVV/SVH in an upright position. The intensity of SN was higher when the head was tilted 90° toward the affected side compared to other positions. The SVV/SVH displayed an ipsiversive shift, when the head was tilted toward both the lesion and unaffected sides, exhibiting a contraversive direction. Furthermore, the changes in position-induced SN were consistent with the displacements of SVV and SVH caused by head tilt. CONCLUSION: The presence of SN in patients with VN was observed to vary across different head position. These variations could potentially be attributed to the diverse activation patterns of the mechanical properties of otolith organs that are induced by head tilts.

Revision for Solid-Body Breakage of the 3D-Printed Implant Following Joint-Sparing Surgery: A Technical Note.

BACKGROUND: The advent of three-dimensional (3D)-printed custom-made implants has revolutionized orthopaedic surgery, particularly in limb- and joint-sparing surgeries. However, clinical experience in the revision for 3D-printed implant breakage is lacking, and the revision surgery remains challenging. This study reported the revision of proximal tibial prosthetic reconstruction necessitated by solid-body breakage of a 3D-printed implant, aiming to detail the surgical techniques and evaluate postoperative outcomes. CASE PRESENTATION: A patient diagnosed with osteosarcoma underwent joint-sparing surgery with a 3D-printed implant, but implant breakage occurred during subsequent follow-up. The initial implant was broken into two parts: the proximal implant breakage part (IBP) integrated with the host bone and the distal IBP left in the prosthetic component. Four revision protocols were devised, each based on one of the four hypothesis results of taking out the initial implant. A new custom-made implant and a series of assistance devices ("positioning devices," "drill devices," "tap devices," and "separator devices") were specifically prepared for revision surgery. The proximal IBP was taken out from the host bone, but the distal IBP was not taken out from the initial prosthetic component. The patient received the new custom-made implant for reconstruction, with the knee joint preserved. The patient recovered uneventfully after revision surgery and achieved satisfactory function. The Musculoskeletal Tumor Society was 28 at the last follow-up. No complications were detected during the follow-up period. CONCLUSION: Comprehensive preoperative planning and preparation, enabling the surgeon to effectively address intraoperative challenges, are crucial for the successful revision of 3D-printed implant breakage. It is feasible to re-implant a 3D-printed custom-made implant, demonstrating satisfactory clinical and functional results.

Inhibition of CISD1 attenuates cisplatin-induced hearing loss in mice via the PI3K and MAPK pathways.

Cisplatin is an effective chemotherapeutic drug for different cancers, but it also causes severe and permanent hearing loss. Oxidative stress and mitochondrial dysfunction in cochlear hair cells (HCs) have been shown to be important in the pathogenesis of cisplatin-induced hearing loss (CIHL). CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) plays a critical role in mitochondrial oxidative capacity and cellular bioenergetics. Targeting CISD1 may improve mitochondrial function in various diseases. However, the role of CISD1 in cisplatin-induced ototoxicity is unclear. Therefore, this study was performed to assess the role of CISD1 in cisplatin-induced ototoxicity. We found that CISD1 expression was significantly increased after cisplatin treatment in both HEI-OC1 cells and cochlear HCs. Moreover, pharmacological inhibition of CISD1 with NL-1 inhibited cell apoptosis and reduced mitochondrial reactive oxygen species accumulation in HEI-OC1 cells and cochlear explants. Inhibition of CISD1 with small interfering RNA in HEI-OC1 cells had similar protective effects. Furthermore, NL-1 protected against CIHL in adult C57 mice, as evaluated by the auditory brainstem response and immunofluorescent staining. Mechanistically, RNA sequencing revealed that NL-1 attenuated CIHL via the PI3K and MAPK pathways. Most importantly, NL-1 did not interfere with the antitumor efficacy of cisplatin. In conclusion, our study revealed that targeting CISD1 with NL-1 reduced reactive oxygen species accumulation, mitochondrial dysfunction, and apoptosis via the PI3K and MAPK pathways in HEI-OC1 cell lines and mouse cochlear explants in vitro, and it protected against CIHL in adult C57 mice. Our study suggests that CISD1 may serve as a novel target for the prevention of CIHL.

Biomimetic design and clinical application of Ti-6Al-4V lattice hemipelvis prosthesis for pelvic reconstruction.

OBJECTIVE: This study aims to biomimetic design a new 3D-printed lattice hemipelvis prosthesis and evaluate its clinical efficiency for pelvic reconstruction following tumor resection, focusing on feasibility, osseointegration, and patient outcomes. METHODS: From May 2020 to October 2021, twelve patients with pelvic tumors underwent tumor resection and subsequently received 3D-printed lattice hemipelvis prostheses for pelvic reconstruction. The prosthesis was strategically incorporated with lattice structures and solid to optimize mechanical performance and osseointegration. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. RESULTS: Multiple pore sizes were observed in irregular porous structures, with a wide distribution range (approximately 300-900 µm). The average follow-up of 34.7 months, ranging 26 from to 43 months. One patient with Ewing sarcoma died of pulmonary metastasis 33 months after surgery while others were alive at the last follow-up. Postoperative radiographs showed that the prosthesis's position was consistent with the preoperative planning. T-SMART images showed that the host bone was in close and tight contact with the prosthesis with no gaps at the interface. The average MSTS score was 21 at the last follow-up, ranging from 18 to 24. There was no complication requiring revision surgery or removal of the 3D-printed hemipelvis prosthesis, such as infection, screw breakage, and prosthesis loosening. CONCLUSION: The newly designed 3D-printed lattice hemipelvis prosthesis created multiple pore sizes with a wide distribution range and resulted in good osteointegration and favorable limb function.

3D-Printed Personalized Lattice Implant as an Innovative Strategy to Reconstruct Geographic Defects in Load-Bearing Bones.

OBJECTIVE: Geographic defect reconstruction in load-bearing bones presents formidable challenges for orthopaedic surgeon. The use of 3D-printed personalized implants presents a compelling opportunity to address this issue. This study aims to design, manufacture, and evaluate 3D-printed personalized implants with irregular lattice porous structures for geographic defect reconstruction in load-bearing bones, focusing on feasibility, osseointegration, and patient outcomes. METHODS: This retrospective study involved seven patients who received 3D-printed personalized lattice implants for the reconstruction of geographic defects in load-bearing bones. Personalized implants were customized for each patient. Randomized dodecahedron unit cells were incorporated within the implants to create the porous structure. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. Tomosynthesis-Shimadzu metal artifact reduction technology (T-SMART) was utilized to evaluate osseointegration. Functional outcomes were assessed according to the Musculoskeletal Tumor Society (MSTS) 93 score. RESULTS: Multiple pore sizes were observed in porous structures of the implant, with a wide distribution range (approximately 300-900 um). The porosity analysis results showed that the average porosity of irregular porous structures was around 75.03%. The average follow-up time was 38.4 months, ranging from 25 to 50 months. Postoperative X-rays showed that the implants matched the geographic bone defect well. Osseointegration assessments according to T-SMART images indicated a high degree of bone-to-implant contact, along with favorable bone density around the implants. Patient outcomes assessments revealed significant improvements in functional outcomes, with the average MSTS score of 27.3 (range, 26-29). There was no implant-related complication, such as aseptic loosening or structure failure. CONCLUSION: 3D-printed personalized lattice implants offer an innovative and promising strategy for geographic defect reconstruction in load-bearing bones. This approach has the potential to match the unique contours and geometry of the geographic bone defect and facilitate osteointegration.

Three-dimensional printed custom-made modular talus prosthesis in patients with talus malignant tumor resection.

BACKGROUND: Talar malignant tumor is extremely rare. Currently, there are several alternative management options for talus malignant tumor including below-knee amputation, tibio-calcaneal arthrodesis, and homogenous bone transplant while their shortcomings limited the clinical application. Three-dimensional (3D) printed total talus prosthesis in talus lesion was reported as a useful method to reconstruct talus, however, most researches are case reports and its clinical effect remains unclear. Therefore, the current study was to explore the application of 3D printed custom-made modular prosthesis in talus malignant tumor. METHODS: We retrospectively analyzed the patients who received the 3D printed custom-made modular prosthesis treatment due to talus malignant tumor in our hospital from February 2016 to December 2021. The patient's clinical data such as oncology outcome, operation time, and volume of blood loss were recorded. The limb function was evaluated with the Musculoskeletal Tumor Society 93 (MSTS-93) score, The American Orthopedic Foot and Ankle Society (AOFAS) score; the ankle joint ranges of motion as well as the leg length discrepancy were evaluated. Plain radiography and Tomosynthesis-Shimadzu Metal Artefact Reduction Technology (T-SMART) were used to evaluate the position of prosthesis and the osseointegration. Postoperative complications were recorded. RESULTS: The average patients' age and the follow-up period were respectively 31.5 ± 13.1 years; and 54.8 months (range 26-72). The medium operation time was 2.4 ± 0.5 h; the intraoperative blood loss was 131.7 ± 121.4 ml. The mean MSTS-93 and AOFAS score was 26.8 and 88.5 respectively. The average plantar flexion, dorsiflexion, varus, and valgus were 32.5, 9.2, 10.8, and 5.8 degree respectively. One patient had delayed postoperative wound healing. There was no leg length discrepancy observed in any patient and good osseointegration was observed on the interface between the bone and talus prosthesis in all subjects. CONCLUSION: The modular structure of the prosthesis developed in this study seems to be convenient for prosthesis implantation and screws distribution. And the combination of solid and porous structure improves the initial stability and promotes bone integration. Therefore, 3D printed custom-made modular talus prosthesis could be an alternative option for talus reconstruction in talus malignant tumor patients.

Efficacy and safety of anlotinib in patients with desmoid fibromatosis: a retrospective analysis.

Introduction: Desmoid fibromatosis is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Targeted therapy for Desmoid fibromatosis represents a novel avenue in systemic treatment. Anlotinib, a novel multitargeted angiogenesis inhibitor, represents a novel approach for targeted therapy. Therefore, this study aims to assess the efficacy and safety of anlotinib in patients with Desmoid fibromatosis. Methods: We retrospectively gathered the clinical medical records of Desmoid fibromatosis patients who underwent anlotinib treatment between June 2019 and November 2023 at our center. Anlotinib was initiated at a daily dose of 12 mg and adjusted based on drug-related toxicity. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival served as the primary endpoint and was analyzed utilizing the Kaplan-Meier method. Results: In total, sixty-six consecutive patients were enrolled. No patients achieved a complete response; however, fourteen patients (21.21%) exhibited a partial response, while forty-six patients (70%) experienced disease stability. Progressive disease was observed in 6 patients (9.10%), and the progression-free survival rates at 12 and 36months were 89.71% and 82.81%, respectively. The disease control rate was 90.91%, while the objective response rate was 21.21%. Conclusion: Anlotinib proves effective in managing recurrent and symptomatic patients with Desmoid fibromatosis. However, the toxicity profile of anlotinib presents a higher risk of Hand-Foot Skin Reaction and hypertension. Therefore, given that 41.67% of patients were subjected to dose adjustments associated with the initial dose of 12 mg, implementing dosage reductions may help balance efficacy with side effects.

Intercalary Prosthetic Reconstruction with Three-Dimensional-Printed Custom-Made Porous Component for Defects of Long Bones with Short Residual Bone Segments After Tumor Resection.

BACKGROUND: Intercalary reconstruction for patients with short residual bone segments remains challenging. Three-dimensional (3D)-printed custom-made porous implants are a promising technique for short-segment fixation in these patients. This study aims to evaluate the efficiency of 3D-printed custom-made porous components (3DCPCs) for short-segment fixation, focusing on prosthesis survivorship, radiographic results, and potential complications. METHODS: This retrospective study involved 39 patients who underwent intercalary prosthetic reconstruction with 3DCPCs after tumor resection of the femur, tibia, or humerus from June 2015 to October 2020. Segment bone loss involved the femur (n = 15), tibia (n = 16), and humerus (n = 8), leaving 78 residual bone segments. There were 46 short segments requiring 46 3DCPCs and 32 segments with the ability to accommodate 32 off-the-shelf standard uncemented stems for prosthesis fixation. Clinical and functional outcomes were evaluated. Prosthesis-overall survivorship and prosthesis-specific survivorship were analyzed using Kaplan-Meier survival analysis. Radiographic results and modes of failure of using this technique were also examined. RESULTS: The mean follow-up was 41 months. The prosthesis-overall survivorship was 87.2% and 84.6% at 2 and 5 years, respectively. The prosthesis-specific survivorship was 92.1% and 89.5% at 2 and 5 years, respectively. There was not a substantial difference in prosthesis survivorship among the femur, tibia, and humerus. The average MSTS score was 26.2, ranging from 22 to 28. The radiographic evaluation results revealed excellent or good interface (38/46) in most of the 46 porous components. A total of 38 of 46 bone segments' remolding demonstrated no change. In total, seven patients (16.3%) had complications requiring further surgery. CONCLUSION: The prosthesis survivorship of using 3DCPCs for short-segment fixation is similar or better compared to other studies involving intercalary prosthetic reconstruction with short-segment fixation. Radiographic evaluation revealed good osteointegration and avoidance of stress shielding. Overall, intercalary prosthetic reconstruction with 3DCPC is a feasible modality for patients with short residual bone segments after tumor resection.

3D-printed Personalized Porous Acetabular Component to Reconstruct Extensive Acetabular Bone Defects in Primary Hip Arthroplasty.

OBJECTIVE: Management of extensive acetabular bone defects in total hip arthroplasty (THA) remains challenging. This study aims to investigate the feasibility and preliminary outcomes of 3D-printed personalized porous acetabular components for the reconstruction of acetabular defects in primary THA. METHODS: This retrospective study involved seven patients who received 3D-printed acetabular components in primary THA between July 2018 and March 2021. Preoperatively, acetabular bone defects were evaluated by referencing the Paprosky classification. There were two "Paprosky type IIIA" defects and five "Paprosky type IIIB" defects. The acetabular components were custom-made for each patient to reconstruct the extensive acetabular defects. The hip function was assessed according to the Harris hip score (HHS). Clinical and radiographic outcomes were assessed. RESULTS: The average follow-up period was 40 months, ranging from 26 to 57 months. There were no patients lost to follow-up. The HHS improved from 44 (range: 33-53) before the operation to 88 (range: 79-93) at the final follow-up. Postoperative X-rays showed that the 3D-printed personalized components were properly fitted with the acetabulum. The average center of rotation (COR) discrepancy was 2.3 mm horizontally and 2.1 mm vertically, respectively. Tomosynthesis-Shimadzu metal artifact reduction technology images showed that the implant was in close contact with the host bone. Moreover, no complications were observed during the follow-up period, including loosening, dislocation, or component protrusion. CONCLUSION: The implantation of 3D-printed personalized acetabular components showed accurate reconstruction, stable mechanical support, and favorable function at short-term follow-up. This may be a viable alternative method for reconstructing extensive acetabular defects in THA.

An integrative pharmacology-based study on the efficacy and mechanism of essential oil of Chaihu Guizhi Decoction on influenza A virus induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

A non-image-forming visual circuit mediates the innate fear of heights in male mice.

The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.

Nanosilicate-reinforced GelMA-PEGDA hydrogel promotes angiogenesis for bone regeneration.

Bone tissue engineering has emerged as a pivotal field addressing the critical clinical needs of bone fractures. This study focused on developing multi-composite hydrogels by synergizing biocompatible GelMA macromolecules with synthetic PEGDA and reinforcing them with nanosilicates (SN). The incorporation of SN introduces crucial trace elements such as silicon, magnesium, and lithium, promoting both angiogenesis and osteogenesis. Characterizations revealed that PEGDA significantly reinforced the composite hydrogels' stability, while SN further enhanced the mechanical integrity of the GelMA-PEGDA-SN (GPS) hydrogels. Cell studies designated that GPS improved cell proliferation and migration, angiogenic VEGF/eNOS expression and osteogenic differentiation. In vivo experiments showed that GPS hydrogels effectively enhanced calvarial bone healing, with the GPS-2 formulation (2 % SN) displaying superior bone coverage and increased vascular formation. Assessments of osteogenic formation and the angiogenic marker CD31 validated the comprehensive bone regeneration potential of GPS hydrogels. These findings highlight the significant promise of GPS hydrogels in fostering bone healing with promoted angiogenesis.

A systematic analysis of diagnostic performance for Alzheimer's disease using structural MRI.

Background: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the elderly. Although numerous structural magnetic resonance imaging (sMRI) studies have reported diagnostic models that could distinguish AD from normal controls (NCs) with 80-95% accuracy, limited efforts have been made regarding the clinically practical computer-aided diagnosis (CAD) system for AD. Objective: To explore the potential factors that hinder the clinical translation of the AD-related diagnostic models based on sMRI. Methods: To systematically review the diagnostic models for AD based on sMRI, we identified relevant studies published in the past 15 years on PubMed, Web of Science, Scopus, and Ovid. To evaluate the heterogeneity and publication bias among those studies, we performed subgroup analysis, meta-regression, Begg's test, and Egger's test. Results: According to our screening criterion, 101 studies were included. Our results demonstrated that high diagnostic accuracy for distinguishing AD from NC was obtained in recently published studies, accompanied by significant heterogeneity. Meta-analysis showed that many factors contributed to the heterogeneity of high diagnostic accuracy of AD using sMRI, which included but was not limited to the following aspects: (i) different datasets; (ii) different machine learning models, e.g. traditional machine learning or deep learning model; (iii) different cross-validation methods, e.g. k-fold cross-validation leads to higher accuracies than leave-one-out cross-validation, but both overestimate the accuracy when compared to validation in independent samples; (iv) different sample sizes; and (v) the publication times. We speculate that these complicated variables might be the adverse factor for developing a clinically applicable system for the early diagnosis of AD. Conclusions: Our findings proved that previous studies reported promising results for classifying AD from NC with different models using sMRI. However, considering the many factors hindering clinical radiology practice, there would still be a long way to go to improve.