Pharmacokinetic Analyses of a Lipid Nanoparticle-Encapsulated mRNA-Encoded Antibody against Rift Valley Fever Virus.

Rift Valley fever virus (RVFV) could cause an emergency illness characterized by fever, muscle pain, and even death in humans or ruminants. However, there are no approved antiviral drugs that prevent or treat RVFV infection. While therapeutic antibodies have shown promising potential for prevention or treatment in several studies, many studies are ongoing, especially in the field of infectious diseases. Among these studies, the mRNA-LNP platform shows great potential for application, following the COVID-19 pandemic. Previously, we have obtained a neutralizing antibody against RVFV, which was named A38 protein and verified to have a high binding and neutralization ability. In this study, we aimed to identify an effectively optimized sequence and expressed the prioritized mRNA-encoded antibody in vitro. Notably, we effectively expressed mRNA-encoded protein and used the mRNA-LNP platform to generate A38-mRNA-LNP. Pharmacokinetic experiments were conducted in vivo and set up in two groups of mRNA-A38 group and A38 protein group, which were derived from mRNA-LNP and plasmid DNA-expressed proteins, respectively. A38-mRNA-LNPs were administrated by intramuscular injection, A38 proteins were administrated by intravenous administration, and their unique ability to maintain long-lasting protein concentrations by mRNA-encoded protein was demonstrated with the mRNA-encoded protein providing a longer circulating half-life compared to injection of the free A38 protein. These preclinical data on the mRNA-encoded antibody highlighted its potential to prevent infectious diseases in the future.

Construction of a Dual-Function Mo-ZIS@Ti for Photocatalytic Benzyl Alcohol Oxidation and Hydrogen Evolution Performance.

The photocatalytic oxidation of benzyl alcohol and the simultaneous evolution of hydrogen from water are efficient dual-optimal routes. It is important to develop composite catalysts that combine redox properties and facilitate electron-hole separation and transport. Herein, the bimetallic-doped Mo-ZIS@Ti photocatalyst was designed and synthesized, and the selective oxidation of benzyl alcohol and hydrogen evolution by water splitting was realized at the same time. Under visible light irradiation, benzyl alcohol was completely converted with more than 99% selectivity for benzaldehyde, and the H2 production rate was 5.6 times higher than the initial ZIS. The exceptional catalytic performance was ascribed to utilizing Ti-MIL-125 as a precursor, wherein slowly releasing-doped Ti formed robust Ti-S bonds that quickly transfer electrons and reduce sites. Meanwhile, doping Mo effectively captures photogenerated holes and acts as active sites for oxidation reactions. Both experimental characterization and work function calculations demonstrate that the bimetallic synergism effectively modulates the electronic structure of ZIS, promotes the directional separation of electrons and holes, and significantly improves the photoactivity and stability of ZIS. This work contributes a route to obtain benzaldehyde and green hydrogen at the same time and also gives new insights for the construction and mechanism study of bimetallic-doping catalysts.

Speciation and Possible Origins of Organosulfur Compounds in Rice Paddy Soils Affected by Acid Mine Drainage.

Although sulfur cycling in acid mine drainage (AMD)-contaminated rice paddy soils is critical to understanding and mitigating the environmental consequences of AMD, potential sources and transformations of organosulfur compounds in such soils are poorly understood. We used sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy to quantify organosulfur compounds in paddy soils from five AMD-contaminated sites and one AMD-uncontaminated reference site near the Dabaoshan sulfide mining area in South China. We also determined the sulfur stable isotope compositions of water-soluble sulfate (δ34SWS), adsorbed sulfate (δ34SAS), fulvic acid sulfur (δ34SFAS), and humic acid sulfur (δ34SHAS) in these samples. Organosulfate was the dominant functional group in humic acid sulfur (HAS) in both AMD-contaminated (46%) and AMD-uncontaminated paddy soils (42%). Thiol/organic monosulfide contributed a significantly lower proportion of HAS in AMD-contaminated paddy soils (8%) compared to that in AMD-uncontaminated paddy soils (21%). Within contaminated soils, the concentration of thiol/organic monosulfide was positively correlated with cation exchange capacity (CEC), moisture content (MC), and total Fe (TFe). δ34SFAS ranged from -6.3 to 2.7‰, similar to δ34SWS (-6.9 to 8.9‰), indicating that fulvic acid sulfur (FAS) was mainly derived from biogenic S-bearing organic compounds produced by assimilatory sulfate reduction. δ34SHAS (-11.0 to -1.6‰) were more negative compared to δ34SWS, indicating that dissimilatory sulfate reduction and abiotic sulfurization of organic matter were the main processes in the formation of HAS.

MicroRNA-671-5p regulates the inflammatory response of periodontal ligament stem cells via the DUSP8/p38 MAPK pathway.

BACKGROUND: MicroRNAs are differentially expressed in periodontitis tissues. They are involved in cellular responses to inflammation and can be used as markers for diagnosing periodontitis. Microarray analysis showed that the expression level of microRNA-671-5p in periodontal tissues of patients with periodontitis was increased. In this study, we investigated the mechanism of action of microRNA-671-5p in human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. METHODS AND RESULTS: HPDLSCs were treated with lipopolysaccharide (LPS) to establish an inflammation model. The cell survival rate was determined using the cell counting kit-8 (CCK8). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of microRNA-671-5p and dual-specificity phosphatase (DUSP) 8 proteins, respectively, Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were detected using qRT-PCR and Enzyme-linked immunosorbent assay (ELISA). A dual-luciferase reporter system was employed to determine the relationship between micoRNA-671-5p and DUSP8 expression. Activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway was confirmed using western blot analysis. Following the treatment of hPDLSCs with LPS, the expression levels of microRNA-671-5p in hPDLSCs were increased, cell viability decreased, and the expression of inflammatory factors displayed an increasing trend. MicroRNA-671-5p targets and binds to DUSP8. Silencing microRNA-671-5p or overexpressing DUSP8 can improve cell survival rate and reduce inflammatory responses. When DUSP8 was overexpressed, the expression of p-p38 was reduced. CONCLUSIONS: microRNA-671-5p targets DUSP8/p38 MAPK pathway to regulate LPS-induced proliferation and inflammation in hPDLSCs.

Telemedicine network latency management system in 5G telesurgery: a feasibility and effectiveness study.

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.

Combination of androgen and estrogen improves asthma by mediating Runx3 expression.

Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4+ T cells to differentiate into Th1 cells. Hence, our study aimed to explore the potential regulatory mechanism of androgen and estrogen on asthma via modulating Runx3. Methods: First, clinical assessments and pulmonary function tests were conducted on 35 asthma patients and 24 healthy controls. The concentrations of androgen, estrogen, and androgen estrogen ratios were assessed in peripheral blood samples of asthma patients and healthy controls. Then, a murine asthma model was established to explore the effects of estrogen and androgen (alone or in combination) on asthma. Third, an in vitro assay was used to explore the mechanism of combination of androgen and estrogen in asthma. Results: We observed decreased androgen and increased estrogen levels in asthma patients compared with healthy controls. In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured with bronchial epithelial cells (BECs), treatment with androgen plus estrogen combination promoted Th1 differentiation, which was mitigated by Runx3 knockdown in BECs and enhanced by Runx3 overexpression. Conclusion: These findings suggest that androgen estrogen combination modulate the Th1/Th2 balance via regulating the expression of Runx3 in BECs, thereby providing experimental evidence supporting androgen and estrogen combination as a novel therapy for asthma.

Development and validation of a nomogram to predict the risk of residual low back pain after tubular microdiskectomy of lumbar disk herniation.

OBJECTIVE: Tubular microdiskectomy (tMD) is one of the most commonly used for treating lumbar disk herniation. However, there still patients still complain of persistent postoperative residual low back pain (rLBP) postoperatively. This study attempts to develop a nomogram to predict the risk of rLBP after tMD. METHODS: The patients were divided into non-rLBP (LBP VAS score < 2) and rLBP (LBP VAS score ≥ 2) group. The correlation between rLBP and these factors were analyzed by multivariate logistic analysis. Then, a nomogram prediction model of rLBP was developed based on the risk factors screened by multivariate analysis. The samples in the model are randomly divided into training and validation sets in a 7:3 ratio. The Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the diskrimination, calibration and clinical value of the model, respectively. RESULTS: A total of 14.3% (47/329) of patients have persistent rLBP. The multivariate analysis suggests that higher preoperative LBP visual analog scale (VAS) score, lower facet orientation (FO), grade 2-3 facet joint degeneration (FJD) and moderate-severe multifidus fat atrophy (MFA) are risk factors for postoperative rLBP. In the training and validation sets, the ROC curves, calibration curves, and DCAs suggested the good diskrimination, predictive accuracy between the predicted probability and actual probability, and clinical value of the model, respectively. CONCLUSION: This nomogram including preoperative LBP VAS score, FO, FJD and MFA can serve a promising prediction model, which will provide a reference for clinicians to predict the rLBP after tMD.

Noble Metal Nanoparticle-Based Photothermal Therapy: Development and Application in Effective Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.

Mitochondrial impairment and downregulation of Drp1 phosphorylation underlie the antiproliferative and proapoptotic effects of alantolactone on oral squamous cell carcinoma cells.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. METHODS: The OSCC cells were treated with varying concentrations and duration of ALT and N-Acetyl-L-cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. RESULTS: ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. CONCLUSIONS: ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.

Electrophysiological responses of the left atrial appendage during pulsed-field electrical isolation utilizing a novel device in a canine model.

BACKGROUND: The electrophysiological responses of the left atrial appendage (LAA) during pulsed-field electrical isolation have not been established. OBJECTIVE: This study aims to investigate the electrical responses of the LAA during pulsed-field electrical isolation using a novel device and their relations to acute isolation success. METHODS: Six canines were enrolled. The E-SeaLA™ device, which is able to perform LAA occlusion and ablation simultaneously, was deployed into the LAA ostium. LAA potentials (LAAp) were mapped via a mapping catheter, and the LAAp recovery time (LAAp RT, the time between the last pulsed spike and the first recovered LAAp) was measured after pulsed-train delivery. The initial pulse index (PI, corelated to pulsed-field intensity) was adjusted during the ablation procedure until LAAEI was achieved. Acute LAA electrical isolation (LAAEI) success was defined as LAAp disappearance or exit and entrance conduction block, confirmed through a drug test and a 60-minute waiting period. RESULT: All canines achieved successful LAA occlusion without peri-device leaks. Acute LAA electrical isolation (LAAEI) was achieved in five out of six canines (5/6, 83.3%). Very late LAAp recurrence (LAAp RT > 600 s) was observed during PFA. Early recurrence (LAAp RT < 30 s) was observed in two canines (2/6, 33.3%) post-PFA. Intermediate recurrence (LAAp RT ~ 120 s) was observed in three canines (3/6, 50%) post-PFA. The two canines with intermediate recurrence achieved LAAEI with higher PI ablations. The one canine with early LAAp recurrence had a peri-device leak and achieved LAAEI by the same PI after replacing with a larger size device and eliminating the peri-device leak. Another canine with early recurrence (1/6, 16.7%) failed to achieve LAAEI due to epicardial connection with persistent left superior vena cava. No coronary spasm, stenosis or other complications were observed. CONCLUSION: These results suggest that with proper device-tissue contact and pulse intensity, LAAEI can be achieved using this novel device without serious complications. The LAAp RT patterns observed in this study could inform and guide the adjustment of the ablation strategy.

Loss of MBD2 ameliorates LPS-induced alveolar epithelial cell apoptosis and ALI in mice via modulating intracellular zinc homeostasis.

Apoptosis of alveolar epithelial cells is a critical initial link in the pathogenesis of acute lung injury (ALI), recent studies have revealed that Methyl-CpG binding domain protein 2 (MBD2) was involved in the execution of apoptosis, yet its role in ALI remained unclear. In the present study, we aim to explore the role and mechanism of MBD2 in the pathogenesis of ALI. We have found that MBD2 expression, in parallel to apoptosis, increased in alveolar epithelial cells of mice treated with LPS, knockout of MBD2 reduced apoptosis and protected mice from LPS-induced ALI. In MLE-12 cells, a cell line of murine alveolar epithelial cells, LPS induced MBD2 expression and apoptosis in a dose- and time-dependent manner. Knockdown of MBD2 with shRNA alleviated, while overexpression of MBD2 increased LPS-induced apoptosis. Mechanistically, intracellular zinc level decreased when MLE-12 cells were treated with LPS. MBD2 knockdown restored intracellular zinc level after LPS treatment, and MBD2 overexpression further aggravated LPS-induced intracellular zinc loss. Metal transcription factor 1 (MTF1) is a critical transcription factor in charge of intracellular zinc efflux. LPS treatment induced MTF1 expression both in vivo and in vitro. Inhibition of MTF1 reduced LPS-induced apoptosis in MLE-12 cells. MBD2 could bind to the promoter region of MTF1 and promote MTF1 expression. Collectively, these data indicated that loss of MBD2-ameliorated LPS-induced alveolar epithelial cell apoptosis and ALI in mice via modulating intracellular zinc homeostasis by upregulating MTF1.

ChK1 activation induces reactive astrogliosis through CIP2A/PP2A/STAT3 pathway in Alzheimer's disease.

Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is upregulated and causes reactive astrogliosis, synaptic degeneration, and cognitive deficits in Alzheimer's disease (AD). However, the mechanism underlying the increased CIP2A expression in AD brains remains unclear. We here demonstrated that the DNA damage-related Checkpoint kinase 1 (ChK1) is activated in AD human brains and 3xTg-AD mice. ChK1-mediated CIP2A overexpression drives inhibition of PP2A and activates STAT3, then leads to reactive astrogliosis and neurodegeneration in vitro. Infection of mouse brain with GFAP-ChK1-AAV induced AD-like cognitive deficits and exacerbated AD pathologies in vivo. In conclusion, we showed that ChK1 activation induces reactive astrogliosis, degeneration of neurons, and exacerbation of AD through the CIP2A-PP2A-STAT3 pathway, and inhibiting ChK1 may be a potential therapeutic approach for AD treatment.

Hepatocytic ballooning in non-alcoholic steatohepatitis: Dilemmas and future directions.

Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in 'real life' situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.

Simultaneous nitrogen and sulfur removal through synergy of sulfammox, anammox and sulfur-driven autotrophic denitrification in a modified bioreactor enhanced by activated carbon.

Anaerobic ammonium (NH4+ - N) oxidation coupled with sulfate (SO42-) reduction (sulfammox) is a new pathway for the autotrophic removal of nitrogen and sulfur from wastewater. Sulfammox was achieved in a modified up-flow anaerobic bioreactor filled with granular activated carbon. After 70 days of operation, the NH4+ - N removal efficiency almost reached 70%, with activated carbon adsorption and biological reaction accounting for 26% and 74%, respectively. Ammonium hydrosulfide (NH4SH) was found in sulfammox by X-ray diffraction analysis for the first time, which confirmed that hydrogen sulfide (H2S) was one of the sulfammox products. Microbial results indicated that NH4+ - N oxidation and SO42- reduction in sulfammox were carried out by Crenothrix and Desulfobacterota, respectively, in which activated carbon may operate as electron shuttle. In the 15NH4+ labeled experiment, 30N2 were produced at a rate of 34.14 µmol/(g sludge·h) and no 30N2 was detected in the chemical control group, proving that sulfammox was present and could only be induced by microorganisms. The 15NO3- labeled group produced 30N2 at a rate of 88.77 µmol/(g sludge·h), demonstrating the presence of sulfur-driven autotrophic denitrification. In the adding 14NH4+ and 15NO3- group, it was confirmed that NH4+ - N was removed by the synergy of sulfammox, anammox and sulfur-driven autotrophic denitrification, where the main product of sulfammox was nitrite (NO2-) and anammox was the main cause of nitrogen loss. The findings showed that SO42- as a non-polluting species to environment may substitute NO2- to create a new "anammox" process.

Exploration of the molecular mechanism of tea polyphenols against pulmonary hypertension by integrative approach of network pharmacology, molecular docking, and experimental verification.

Pulmonary hypertension, a common complication of chronic obstructive pulmonary disease, is a major global health concern. Green tea is a popular beverage that is consumed all over the world. Green tea's active ingredients are epicatechin derivatives, also known as "polyphenols," which have anti-carcinogenic, anti-inflammatory, and antioxidant properties. This study aimed to explore the possible mechanism of green tea polyphenols in the treatment of pulmonary hypertension using network pharmacology, molecular docking, and experimental verification. A total of 316 potential green tea polyphenols-related targets were obtained from the PharmMapper, SwissTargetPrediction, and TargetNet databases. A total of 410 pulmonary hypertension-related targets were predicted by the CTD, DisGeNET, pharmkb, and GeneCards databases. Green tea polyphenols-related targets were hit by the 49 targets associated with pulmonary hypertension. AKT1 and HIF1-α were identified through the FDA drugs-target network and PPI network combined with GO functional annotation and KEGG pathway enrichment. Molecular docking results showed that green tea polyphenols had strong binding abilities to AKT1 and HIF1-α. In vitro experiments showed that green tea polyphenols inhibited the proliferation and migration of hypoxia stimulated pulmonary artery smooth muscle cells by decreasing AKT1 phosphorylation and downregulating HIF1α expression. Collectively, green tea polyphenols are promising phytochemicals against pulmonary hypertension.

Reconstruction of massive bone defects after femoral tumor resection using two new-designed 3D-printed intercalary prostheses: a clinical analytic study with the cooperative utilization of multiple technologies.

BACKGROUND: To reconstruct massive bone defects of the femoral diaphysis and proximal end with limited bilateral cortical bone after joint-preserving musculoskeletal tumor resections, two novel 3D-printed customized intercalary femoral prostheses were applied. METHODS: A series of nine patients with malignancies who received these novel 3D-printed prostheses were retrospectively studied between July 2018 and November 2021. The proximal and diaphyseal femur was divided into three regions of interest (ROIs) according to anatomic landmarks, and anatomic measurements were conducted on 50 computed tomography images showing normal femurs. Based on the individual implant-involved ROIs, osteotomy level, and anatomical and biomechanical features, two alternative 3D-printed prostheses were designed. In each patient, Hounsfield Unit (HU) value thresholding and finite element analysis were conducted to identify the bone trabecula and calcar femorale and to determine the stress distribution, respectively. We described the characteristics of each prosthesis and surgical procedure and recorded the intraoperative data. All patients underwent regular postoperative follow-up, in which the clinical, functional and radiographical outcomes were evaluated. RESULTS: With the ROI division and radiographic measurements, insufficient bilateral cortical bones for anchoring the traditional stem were verified in the normal proximal femur. Therefore, two 3D-printed intercalary endoprostheses, a Type A prosthesis with a proximal curved stem and a Type B prosthesis with a proximal anchorage-slot and corresponding locking screws, were designed. Based on HU value thresholding and finite element analysis, the 3D-printed proximal stems in all prostheses maximally preserved the trabecular bone and calcar femorale and optimized the biomechanical distribution, as did the proximal screws. With the 3D-printed osteotomy guide plates and reaming guide plates, all patients underwent the operation uneventfully with a satisfactory duration (325.00 ± 62.60 min) and bleeding volume (922.22 ± 222.36 ml). In the follow-up, Harris Hip and Musculoskeletal Tumor Society scores were ameliorated after surgery (P < 0.001 and P < 0.001, respectively), reliable bone ingrowth was observed, and no major complications occurred. CONCLUSIONS: Two novel 3D-printed femoral intercalary prostheses, which achieved acceptable overall postoperative outcomes, were used as appropriate alternatives for oncologic patients with massive bone defects and limited residual bone and increased the opportunities for joint-preserving tumor resection. Several scientific methodologies utilized in this study may promote the clinical design proposals of 3D-printed implants.

Middle Meningeal Artery Embolization Combined With Endoscopic Treatment for Chronic Subdural Hematoma.

OBJECTIVE: To explore the clinical feasibility of middle meningeal artery (MMA) embolization combined with endoscopic treatment for new or recurrent chronic subdural hematoma (CSDH). METHODS: Twenty patients with CSDH treated in the Binzhou Medical University Hospital from June 2020 to October 2022 were analyzed retrospectively. The clinical information, prognosis, imaging results, and surgical results of the patients were collected and analyzed. The authors first performed MMA embolization, and then endoscopic treatment of CSDH was performed after successful embolization of MMA. Results: All 20 patients with CSDH were successfully treated with MMA embolization combined with endoscope-assisted evacuation. The symptoms of all patients were relieved, no surgical complications occurred, and no rebleeding and recurrence were found in follow-up computed tomography. CONCLUSION: Middle meningeal artery embolization combined with endoscopic treatment of CSDH has a good clinical effect, and it may prevent postoperative recurrence.

Adenoviral Vector for Enhanced Prostate Cancer Specific Transferrin Conjugated Drug Targeted Therapy.

Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Unlike some other types of cancer, there is a lack of targeted therapy for prostate cancer patients that can kill cancer cells but do much less damage to the normal tissue. In this paper, we report on an adenoviral vector enhanced prostate cancer specific transferrin conjugated drug targeted therapy. In particular, a functional PCa-specific gene probe is introduced to drive and up-regulate the transferrin receptor expression on the PCa via adenoviral vector. As a result, significantly enhanced accumulation of nanoscale transferrin-doxorubicin (Tf-DOX) protein drug conjugates and concomitant notably elevated PCa tumor inhibition are observed. This conceptual strategy provides the proof-of-concept for the targeted therapy of PCa that is highly desired but not yet developed.

A novel three-dimensional-printed patient-specific sacral implant for spinopelvic reconstruction in sacral giant cell tumour.

PURPOSE: Spinopelvic reconstruction after sacral tumour resection is one of the most demanding procedures in sacral tumour surgery. The aims of this study were to evaluate the feasibility of spinopelvic reconstruction with 3D-printed prostheses in sacral giant cell tumours and the clinical outcomes and complications at follow-up. METHODS: We retrospectively analyzed ten consecutive patients with giant cell tumors of the sacrum who underwent intralesional nerve-sparing resection with curative intent and custom implant reconstruction between 2016 and 2021. There were four males and six females with a mean age of 40.2 years (range, 25-62 years) at surgery. A computer-aided-design implant was prepared using 3D printing technology that was both matched to the bone defect and biomechanically evaluated. A 3D-printed surgical guide was used to replicate the resection procedure as planned. We analyzed operational outcomes, oncological outcomes, functional outcomes, complications, and prosthetic outcomes. Pain at rest was assessed according to a 10-cm VAS score. The results of functional improvement were evaluated using the MSTS-93 score at the final follow-up. RESULTS: All patients were observed for 26 to 61 months, with an average follow-up of 43.8 months. No deep infection or prosthetic structural failure occurred in this study. A total of 80% of patients had good neurological function and normal urinary, bowel, and ambulatory functions. The mean MSTS score was 24.1 (range, 22-26). The mean VAS score was 2 (range 0 to 2). Delayed wound healing occurred in three patients, and the wounds healed after debridement. One case had local recurrence and survived tumour-free after resection of the recurrent lesion. An aseptic loosening was found in a patient that did not require secondary surgery. By radiographical assessments, we found that 90% of implants were well osseointegrated at the final follow-up examination. CONCLUSIONS: The 3D-printed sacral implants might provide a promising strategy for spinopelvic reconstruction in sacral giant cell tumours undergoing intralesional nerve-sparing surgery with satisfactory clinical outcomes, osseointegration, and excellent durability.

Genome-Wide Association Study Identifies Resistance Loci for Bacterial Blight in a Collection of Asian Temperate Japonica Rice Germplasm.

Growing resistant rice cultivars is the most effective strategy to control bacterial blight (BB), a devastating disease caused by Xanthomonas oryzae pv. oryzae (Xoo). Screening resistant germplasm and identifying resistance (R) genes are prerequisites for breeding resistant rice cultivars. We conducted a genome-wide association study (GWAS) to detect quantitative trait loci (QTL) associated with BB resistance using 359 East Asian temperate Japonica accessions inoculated with two Chinese Xoo strains (KS6-6 and GV) and one Philippine Xoo strain (PXO99A). Based on the 55K SNPs Array dataset of the 359 Japonica accessions, eight QTL were identified on rice chromosomes 1, 2, 4, 10, and 11. Four of the QTL coincided with previously reported QTL, and four were novel loci. Six R genes were localized in the qBBV-11.1, qBBV-11.2, and qBBV-11.3 loci on chromosome 11 in this Japonica collection. Haplotype analysis revealed candidate genes associated with BB resistance in each QTL. Notably, LOC_Os11g47290 in qBBV-11.3, encoding a leucine-rich repeat receptor-like kinase, was a candidate gene associated with resistance to the virulent strain GV. Knockout mutants of Nipponbare with the susceptible haplotype of LOC_Os11g47290 exhibited significantly improved BB resistance. These results will be useful for cloning BB resistance genes and breeding resistant rice cultivars.