Caffeic acid phenethyl ester promotes oxaliplatin sensitization in colon cancer by inhibiting autophagy.

Colon cancer ranks as the third most prevalent form of cancer globally, with chemotherapy remaining the primary treatment modality. To mitigate drug resistance and minimize adverse effects associated with chemotherapy, selection of appropriate adjuvants assumes paramount importance. Caffeic acid phenethyl ester (CAPE), a naturally occurring compound derived from propolis, exhibits a diverse array of biological activities. We observed that the addition of CAPE significantly augmented the drug sensitivity of colon cancer cells to oxaliplatin. In SW480 and HCT116 cells, oxaliplatin combined with 10 µM CAPE reduced the IC50 of oxaliplatin from 14.24 ± 1.03 and 84.16 ± 3.02 µM to 2.11 ± 0.15 and 3.92 ± 0.17 µM, respectively. We then used proteomics to detect differentially expressed proteins in CAPE-treated SW480 cells and found that the main proteins showing changes in expression after CAPE treatment were p62 (SQSTM1) and LC3B (MAP1LC3B). Gene ontology analysis revealed that CAPE exerted antitumor and chemotherapy-sensitization effects through the autophagy pathway. We subsequently verified the differentially expressed proteins using immunoblotting. Simultaneously, the autophagy inhibitor bafilomycin A1 and the mCherry-EGFP-LC3 reporter gene were used as controls to detect the effect of CAPE on autophagy levels. Collectively, the results indicate that CAPE may exert antitumor and chemotherapy-sensitizing effects by inhibiting autophagy, offering novel insights for the development of potential chemosensitizing agents.

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.

Random forest predictive modeling of prolonged hospital length of stay in elderly hip fracture patients.

Background: In elderly individuals suffering from hip fractures, a prolonged hospital length of stay (PLOS) not only heightens the probability of patient complications but also amplifies mortality risks. Yet, most elderly hip fracture patients present compromised baseline health conditions. Additionally, PLOS leads to increased expenses for patient treatment and care, while also diminishing hospital turnover rates. This, in turn, jeopardizes the prompt allocation of beds for urgent cases. Methods: A retrospective study was carried out from October 2021 to November 2023 on 360 elderly hip fracture patients who underwent surgical treatment at West China Hospital. The 75th percentile of the total patient cohort's hospital stay duration, which was 12 days, was used to define prolonged hospital length of stay (PLOS). The cohort was divided into training and testing datasets with a 70:30 split. A predictive model was developed using the random forest algorithm, and its performance was validated and compared with the Lasso regression model. Results: Out of 360 patients, 103 (28.61%) experienced PLOS. A Random Forest classification model was developed using the training dataset, identifying 10 essential variables. The Random Forest model achieved perfect performance in the training set, with an area under the curve (AUC), balanced accuracy, Kappa value, and F1 score of 1.000. In the testing set, the model's performance was assessed with an AUC of 0.846, balanced accuracy of 0.7294, Kappa value of 0.4325, and F1 score of 0.6061. Conclusion: This study aims to develop a prognostic model for predicting delayed discharge in elderly patients with hip fractures, thereby improving the accuracy of predicting PLOS in this population. By utilizing machine learning models, clinicians can optimize the allocation of medical resources and devise effective rehabilitation strategies for geriatric hip fracture patients. Additionally, this method can potentially improve hospital bed turnover rates, providing latent benefits for the healthcare system.

Nodule-in-nodule architecture of hepatocellular carcinomas: enhancement patterns in the hepatobiliary phase and pathological features.

PURPOSE: This study aimed to evaluate the enhancement patterns in the hepatobiliary phase (HBP) and pathological features of nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) patients. METHODS: In this single-institution retrospective study, 27 consecutive cirrhosis patients with 29 histologically confirmed NIN-HCCs who underwent preoperative examination via Gd-EOB-DTPA-enhanced MRI were enrolled from January 2016 to September 2023. Two blinded radiologists assessed the imaging features of both the inner and outer nodules in NIN-HCCs to reach a consensus on the Liver Imaging Reporting & Data System (LI-RADS) categories of the lesions. Based on the different enhancement patterns of the inner and outer nodules in the HBP, NIN-HCCs were classified into different groups and further divided into different types. Imaging features and LI-RADS categories were subsequently compared among the groups. Pathological findings for NIN-HCCs were also evaluated. RESULTS: Among 29 NIN-HCCs, all inner nodules showed hypervascularity, with a maximum diameter of 13.2 ± 5.5 mm; 51.7% (15/29) showed "wash-in with washout" enhancement; and 48.3% (14/29) showed "wash-in without washout" enhancement. All outer nodules showed hypovascularity, with a maximum diameter of 25.6 ± 7.3 mm, and 51.9% (14/29) showed a washout appearance on PVP. Among all the lesions, the maximum diameter was 27.5 ± 6.8 mm; 12 (41.4%) lesions were LR-4, and 17 (58.6%) lesions were LR-5. NIN-HCCs were classified into hypointense (62.1%, 18/29) and isointense (37.9%, 11/29) groups based on the signal intensity of the outer nodules in the HBP. In the hypointense group, 2 (6.9%) of the inner nodules were hypointense (type A), 11 (37.9%) were isointense (type B), and 5 (17.2%) were hyperintense (type C) compared to the background hypointense outer nodules. In the isointense group, 9 (31.0%) of the inner nodules were hypointense (type D), 2 (6.9%) were isointense (type E), and no (0%) was hyperintense (type F) compared to the background isointense outer nodules. There were no significant differences in the diameter, dynamic enhancement patterns of the inner or outer nodules, or LI-RADS scores of the lesions between the hypointense group and the isointense group (all P > 0.05). Histologically, the inner nodules of NIN-HCCs were mainly composed of moderately differentiated HCC (75.9% 22/29), whereas the outer nodules consisted of either well-differentiated HCC or high-grade dysplastic nodules (HGDNs). CONCLUSIONS: NIN-HCCs exhibit specific MRI findings closely associated with their pathological features. The spectrum of HBP enhancement patterns provides valuable insights into the underlying cell biological mechanisms of these lesions. NIN-HCC subtypes may be used as a morphologic marker in the early stage of multistep hepatocarcinogenesis.

Hybrid Path Generation Method for Multi-Axis Laser Metal Deposition of Overhanging Thin-Walled Structures.

Additive manufacturing has advantages over other traditional manufacturing technologies for the fabrication of complex thin-walled parts. Previous correlation path strategies, when applied to laser metal deposition processes, suffer from contour deposition transboundary and surface "scar" type overstacking. Therefore, this paper proposes a hybrid path generation method for the laser metal deposition process. First, the topological logic of the STL model of the part is restored to reduce redundant calculations at the stage of obtaining the layered contour. Then, the path points are planned on the basis of the offset contours in a helical upward trend to form a globally continuous composite path in space considering the melt channel width. Finally, vectors that adaptively fit to the model surface are generated for the path points as tool orientations and they are optimized by smoothing the rotation angles. The results of experiments conducted on a multi-axis machine equipped with a laser metal deposition module show that the path generated by the proposed method is not only capable of thin-walled structures with overhanging and curved surface features but also improves the surface imperfections of the part due to sudden changes in the angle of rotation while ensuring the boundary dimensions.

The effect of CXCL12 on survival outcomes of patients with viral hepatitis-associated hepatocellular carcinoma after hepatectomy.

Background: The CXCL12-CXCR4/CXCR7 axis is garnering growing attention. But the comprehension of its function in the progression of HCC remains controversial. The purpose of this study was to investigate the effects of CXCL12 and its receptor on the prognosis of patients with viral hepatitis-associated HCC after hepatectomy. Methods: A total of 86 patients had been enrolled who had undergone hepatectomy for HCC and followed up to July 31, 2019, and their clinicopathological and follow-up data were recorded. Tumor and peritumoral tissues were obtained to detect the expression of CXCL12, CXCR4, and CXCR7 using immunohistochemistry. Real-time polymerase chain reaction was utilized to detect hepatitis B or C virus loads, while survival analysis was performed using the Kaplan-Meier method. Furthermore, the Cox proportional hazards regression model was employed to analyze the factors affecting the prognosis. Results: The results revealed that the CXCL12, CXCR4, and CXCR7 expression in tumor tissues was lower than in the corresponding non-tumor tissues in 20.93 %, 22.09 %, and 23.26 % of the patients, respectively, and that only CXCL12 was found to be related to the extrahepatic invasion of HCC. The survival analysis and Cox regression showed that only CXCL12 was associated with the postoperative survival of patients with HCC, and that it was an independent prognostic risk factor in the CXCL12-CXCR4/CXCR7 axis. The CXCL12low group represented shorter progression-free survival and lower overall survival rates. However, the subgroup analysis displayed that the survival difference associated with CXCL12 was only manifested in patients with higher expression of CXCR4 or CXCR7 in HCC, as compared to the surrounding tissues. Conclusions: Our findings suggest that, when assessing the prognostic significance of CXCL12 in HCC, it is essential to consider the expression level of its receptor. Nevertheless, CXCL12 can potentially serve as a promising prognostic marker for HCC.

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Hidden delta degradation due to fluvial sediment decline and intensified marine storms.

Deltas are threatened by erosion due to climate change and reduced sediment supply, but their response to these changes remains poorly quantified. We investigate the abandoned Yellow River delta that has transitioned from rapid growth to ongoing deterioration due to a river avulsion removing the sediment supply. Integrating bathymetric data, process observations, and sediment transport modeling, we find that while the subaerial delta was stabilized by engineering measures, the subaqueous delta continued to erode due to intensified storms, losing 39% of its mass deposited before the avulsion. Long-term observations show that winter storms initiate scouring of the subaqueous delta, contributing up to 70% of seabed erosion. We then analyze 108 global deltas to assess subaqueous delta erosion risks and identify 17 deltas facing similar situations of sediment decline and storm intensification during the past 40 years. Our findings suggest that subaqueous delta erosion must be integrated into delta sustainability evaluations.

Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

A Narrative Review of the Reciprocal Relationship Between Sleep Deprivation and Chronic Pain: The Role of Oxidative Stress.

Sleep is crucial for human health, insufficient sleep or poor sleep quality may negatively affect sleep function and lead to a state of sleep deprivation. Sleep deprivation can result in various health problems, including chronic pain. The intricate relationship between sleep and pain is complex and intertwined, with daytime pain affecting sleep quality and poor sleep increasing pain intensity. The article first describes the influence of sleep on the onset and development of pain, and then explores the impact of daytime pain intensity on nighttime sleep quality and subsequent pain thresholds. However, the primary emphasis is placed on the pivotal role of oxidative stress in this bidirectional relationship. Although the exact mechanisms underlying sleep and chronic pain are unclear, this review focuses on the role of oxidative stress. Numerous studies on sleep deprivation have demonstrated that it can lead to varying degrees of increased pain sensitivity, while chronic pain leads to sleep deprivation and further exacerbates pain. Further research on the role of oxidative stress in the mechanism of sleep deprivation-induced pain sensitization seems reasonable. This article comprehensively reviews the current research on the interrelationship between sleep deprivation, pain and the crucial role of oxidative stress.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Changes in Patellar Height and Tibial Posterior Slope after Biplanar High Tibial Osteotomy with Computer-Designed Personalized Surgical Guides: A Retrospective Study.

OBJECTIVE: Medial opening-wedge high tibial osteotomy (MOWHTO) is a surgical procedure to treat medial compartment osteoarthritis in the knee with varus deformity. However, factors such as patellar height (PH) and the sagittal plane's posterior tibial slope angle (PTSA) are potentially overlooked. This study investigated the impact of alignment correction angle guided by computer-designed personalized surgical guide plate (PSGP) in MOWHTO on PH and PTSA, offering insights for enhancing surgical techniques. METHODS: This retrospective study included patients who underwent 3D-printed PSGP-assisted MOWHTO at our institution from March to September 2022. The paired t-tests assessed differences in all preoperative and postoperative measurement parameters. Multivariate linear regression analysis examined correlations between PTSA, CDI (Caton-Deschamps Index), and the alignment correction magnitude. Receiver operating characteristic (ROC) curve analysis determined the threshold of the correction angle, calculating sensitivity, specificity, and area under the curve. RESULTS: A total of 107 patients were included in our study. The CDI changed from a preoperative mean of 0.97 ± 0.13 (range 0.70-1.34) to a postoperative mean of 0.82 ± 0.13 (range 0.55-1.20). PTSA changed from a preoperative mean of 8.54 ± 2.67 (range 2.19-17.55) to a postoperative mean of 10.54 ± 3.05 (range 4.48-18.05). The t-test revealed statistically significant changes in both values (p < 0.05). A significant alteration in patellar height occurred when the correction angle exceeded 9.39°. Moreover, this paper illustrates a negative correlation between CDI change and the correction angle and preoperative PTSA. Holding other factors constant, each 1-degree increase in the correction angle led to a 0.017 decrease in postoperative CDI, and each 1-degree increase in preoperative PTSA resulted in a 0.008 decrease in postoperative CDI. PTSA change was positively correlated only with the correction angle; for each 1-degree increase in the opening angle, postoperative PTS increased by 0.188, with other factors constant. CONCLUSION: This study highlights the effectiveness and precision of PSGP-assisted MOWHTO, focusing on the impact of alignment correction on PH and PTSA. These findings support the optimization of PSGP technology, which offers simpler, faster, and safer surgeries with less radiation and bleeding than traditional methods. However, PSGP's one-time use design and the learning curve required for its application are limitations, suggesting areas for further research.

Novel self-setting cements based on tricalcium silicate/(ß-tricalcium phosphate/monocalcium phosphate anhydrous)/hydroxypropyl methylcellulose: From hydration mechanism to biological evaluations.

Despite the clinical success of tricalcium silicate (TCS)-based materials in endodontics, the inferior handling characteristic, poor anti-washout property and slow setting kinetics hindered their wider applications. To solve these problems, an injectable fast-setting TCS/ß-tricalcium phosphate/monocalcium phosphate anhydrous (ß-TCP/MCPA) cement was developed for the first time by incorporation of hydroxypropyl methylcellulose (HPMC) and ß-TCP/MCPA. The physical-chemical characterization (setting time, anti-washout property, injectability, compressive strength, apatite mineralization and sealing property) of TCS/(ß-TCP/MCPA) were conducted. Its hydration mechanism was also investigated. Furthermore, the cytocompatibility and osteogenic/odontogenic differentiation of stem cells isolated from human exfoliated deciduous teeth (SHED) treated with TCS/ß-TCP/MCPA were studied. The results showed that HPMC could provide TCS with good anti-washout ability and injectability but slow hydration process. However, ß-TCP/MCPA effectively enhanced anti-washout characteristics and reduced setting time due to faster hydration kinetics. TCS/(ß-TCP/MCPA) obtained around 90 % of injection rate and high compressive strength whereas excessive additions of ß-TCP/MCPA compromised its injectability and compressive strength. TCS/(ß-TCP/MCPA) can induce apatite deposition and form a tight marginal sealing at the dentin-cement interface. Additionally, TCS/(ß-TCP/MCPA) showed good biocompatibility and promoted osteo/odontogenic differentiation of SHED. In general, our results indicated that TCS/(ß-TCP/MCPA) may be particularly promising as an injectable bioactive cements for endodontic treatment.

Cellular functions, molecular signalings and therapeutic applications: Translational potential of deubiquitylating enzyme USP9X as a drug target in cancer treatment.

Protein ubiquitination, one of the most significant post-translational modifications, plays an important role in controlling the proteins activity in diverse cellular processes. The reversible process of protein ubiquitination, known as deubiquitination, has emerged as a critical mechanism for maintaining cellular homeostasis. The deubiquitinases (DUBs), which participate in deubiquitination process are increasingly recognized as potential candidates for drug discovery. Among these DUBs, ubiquitin-specific protease 9× (USP9X), a highly conserved member of the USP family, exhibits versatile functions in various cellular processes, including the regulation of cell cycle, protein endocytosis, apoptosis, cell polarity, immunological microenvironment, and stem cell characteristics. The dysregulation and abnormal activities of USP9X are influenced by intricate cellular signaling pathway crosstalk and upstream non-coding RNAs. The complex expression patterns and controversial clinical significance of USP9X in cancers suggest its potential as a prognostic biomarker. Furthermore, USP9X inhibitors has shown promising antitumor activity and holds the potential to overcome therapeutic resistance in preclinical models. However, a comprehensive summary of the role and molecular functions of USP9X in cancer progression is currently lacking. In this review, we provide a comprehensive delineation of USP9X participation in numerous critical cellular processes, complicated signaling pathways within the tumor microenvironment, and its potential translational applications to combat therapeutic resistance. By systematically summarizing the updated molecular mechanisms of USP9X in cancer biology, this review aims to contribute to the advancement of cancer therapeutics and provide essential insights for specialists and clinicians in the development of improved cancer treatment strategies.

A review of biomacromolecule-based 3D bioprinting strategies for structure-function integrated repair of skin tissues.

When skin is damaged or affected by diseases, it often undergoes irreversible scar formation, leading to aesthetic concerns and psychological distress for patients. In cases of extensive skin defects, the patient's life can be severely compromised. In recent years, 3D printing technology has emerged as a groundbreaking approach to skin tissue engineering, offering promising solutions to various skin-related conditions. 3D bioprinting technology enables the precise fabrication of structures by programming the spatial arrangement of cells within the skin tissue and subsequently printing skin replacements either in a 3D bioprinter or directly at the site of the defect. This study provides a comprehensive overview of various biopolymer-based inks, with a particular emphasis on chitosan (CS), starch, alginate, agarose, cellulose, and fibronectin, all of which are natural polymers belonging to the category of biomacromolecules. Additionally, it summarizes artificially synthesized polymers capable of enhancing the performance of these biomacromolecule-based bioinks, thereby composing hybrid biopolymer inks aimed at better application in skin tissue engineering endeavors. This review paper examines the recent advancements, characteristics, benefits, and limitations of biological 3D bioprinting techniques for skin tissue engineering. By utilizing bioinks containing seed cells, hydrogels with bioactive factors, and biomaterials, complex structures resembling natural skin can be accurately fabricated in a layer-by-layer manner. The importance of biological scaffolds in promoting skin wound healing and the role of 3D bioprinting in skin tissue regeneration processes is discussed. Additionally, this paper addresses the challenges and constraints associated with current 3D bioprinting technologies for skin tissue and presents future perspectives. These include advancements in bioink formulations, full-thickness skin bioprinting, vascularization strategies, and skin appendages bioprinting.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

Research on the Application and Mechanisms of Electroactive Microorganisms in Toxicants Monitoring: A Review.

A biological treatment is the core process for removing organic pollutants from industrial wastewater. However, industrial wastewater often contains large amounts of toxic and harmful pollutants, which can inhibit the activity of microorganisms in a treatment system, precipitate the deterioration of effluent quality, and threaten water ecological security from time to time. In most of the existing anaerobic biological treatment processes, toxic effects on microorganisms are determined according to the amounts of end-products of the biochemical reactions, and the evaluation results are relatively lacking. When microorganisms contact toxic substances, changes in biological metabolic activity precede the accumulation of reaction products. As sensitive units, electroactive microorganisms can generate electrical signals, a change in which can directly reflect the toxicity level. The applications of electroactive microorganisms for the toxicity monitoring of wastewater are very promising. Further attention needs to be paid to considering the appropriate evaluation index, the influence of the environment on test results, mechanisms, and other aspects. Therefore, we reviewed the literature regarding the above aspects in order to provide a research foundation for the practical application of electroactive microorganisms in toxicant monitoring.

A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer.

Triple-positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan-human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin-dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II-III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%-84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0-I was 75% (95% CI, 46.8%-91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5%-70.5%) at baseline to 17.2% (95% CI, 0.7%-33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment-related deaths occurred. This four-drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

Comparative transcriptome analysis reveals the importance of phenylpropanoid biosynthesis for the induced resistance of 84K poplar to anthracnose.

BACKGROUND: Poplar anthracnose, which is one of the most important tree diseases, is primarily caused by Colletotrichum gloeosporioides, which has been detected in poplar plantations in China and is responsible for serious economic losses. The characteristics of 84K poplar that have made it one of the typical woody model plants used for investigating stress resistance include its rapid growth, simple reproduction, and adaptability. RESULTS: In this study, we found that the resistance of 84K poplar to anthracnose varied considerably depending on how the samples were inoculated of the two seedlings in each tissue culture bottle, one (84K-Cg) was inoculated for 6 days, whereas the 84K-DCg samples were another seedling inoculated at the 6th day and incubated for another 6 days under the same conditions. It was showed that the average anthracnose spot diameter on 84K-Cg and 84K-DCg leaves was 1.23 ± 0.0577 cm and 0.67 ± 0.1154 cm, respectively. Based on the transcriptome sequencing analysis, it was indicated that the upregulated phenylpropanoid biosynthesis-related genes in 84K poplar infected with C. gloeosporioides, including genes encoding PAL, C4H, 4CL, HCT, CCR, COMT, F5H, and CAD, are also involved in other KEGG pathways (i.e., flavonoid biosynthesis and phenylalanine metabolism). The expression levels of these genes were lowest in 84K-Cg and highest in 84K-DCg. CONCLUSIONS: It was found that PAL-related genes may be crucial for the induced resistance of 84K poplar to anthracnose, which enriched in the phenylpropanoid biosynthesis. These results will provide the basis for future research conducted to verify the contribution of phenylpropanoid biosynthesis to induced resistance and explore plant immune resistance-related signals that may regulate plant defense capabilities, which may provide valuable insights relevant to the development of effective and environmentally friendly methods for controlling poplar anthracnose.

Multiparametric MRI-based intratumoral and peritumoral radiomics for predicting the pathological differentiation of hepatocellular carcinoma.

PURPOSE: To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. METHODS: A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). RESULTS: Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. CRITICAL RELEVANCE STATEMENT: Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. KEY POINTS: • Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. • The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. • The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation.