Intolerance of uncertainty affects the behavioral and neural mechanisms of higher generalization.

Intolerance of uncertainty (IU) is associated with several anxiety disorders. In this study, we employed rewards and losses as unconditioned positive and negative stimuli, respectively, to explore the effects of an individual's IU level on positive and negative generalizations using magnetic resonance imaging technology. Following instrumental learning, 48 participants (24 high IU; 24 low IU) were invited to complete positive and negative generalization tasks; their behavioral responses and neural activities were recorded by functional magnetic resonance imaging. The behavior results demonstrated that participants with high IUs exhibited higher generalizations to both positive and negative cues as compared with participants having low IUs. Neuroimaging results demonstrated that they exhibited higher activation levels in the right anterior insula and the default mode network (i.e. precuneus and posterior cingulate gyrus), as well as related reward circuits (i.e. caudate and right putamen). Therefore, higher generalization scores and the related abnormal brain activation may be key markers of IU as a vulnerability factor for anxiety disorders.

Method for reconstructing femoral head blood supply by anastomosing the intraosseous artery.

Background: The reconstruction of femoral head blood supply is crucial in the management of avascular necrosis and related conditions. This study presents a method for reconstructing the femoral head blood supply by anastomosing the intraosseous artery. Methods: The femoral heads of six male Landrace swine were surgically exposed, and subcranial fractures of the femoral neck were intentionally created. Under microscopic guidance, the trophoblastic foramen of the posterior supporting artery was identified. Subsequently, a triangular bone window was carefully crafted to expose the intraosseous artery. Following the fixation of the femoral head, an anastomosis was performed between the intraosseous artery and the posterior inferior supporting artery located at the distal end of the fracture. The assessment of femoral head blood supply was conducted using Kirschner's pinhole and angiography techniques. Results: The anastomotic intraosseous artery exhibited a vibrant red color, indicating adequate blood perfusion, and demonstrated pulsatile flow. Observation through pinholes in the surface of the femoral head revealed continuous blood flow. Angiography further confirmed the successful circulation, as the contrast agent entered the inferior retinacular artery branch originating from the deep femoral artery. The contrast agent then proceeded to enter the femoral head through the retinacular artery, reaching the anastomosis site of the intraosseous artery. Notably, the angiography also revealed the presence of visible internal branches, highlighting the establishment of a functional vascular network. Discussion: The method of reconstructing the blood supply to the femoral head through anastomosis of the intraosseous artery enables utilization of the existing blood supply system within the femoral head. This study is just a preliminary study of this innovative technique that has the potential to prevent and/or treat femoral head necrosis following a femoral neck fracture. By restoring adequate blood flow to the affected area, this approach holds promise in preserving the viability and functionality of the femoral head, ultimately improving patient outcomes.

Experimental analysis of femoral head intraosseous vascular anastomosis in the treatment of porcine subcapital femoral neck fractures.

Introduction: Femoral neck fractures are challenging injuries associated with a compromised blood supply to the femoral head, leading to a high risk of avascular necrosis and poor clinical outcomes. This study aimed to investigate the efficacy of femoral head intraosseous vascular anastomosis in the treatment of porcine sub-capital femoral neck fractures. Methods: Ten Landrace pigs were used as experimental animal models. The femoral head was completely removed after femoral neck sub-cephalic fracture. It was fixed on the medial side of the knee joint, and the blood supply to the femoral head was reconstructed by anastomosing the femoral head vessels. One week later, blood flow in the femoral head was observed by borehole, digital subtraction angiography examination, and hematoxylin and eosin staining. Further, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling tests were performed to detect pathological changes in the femoral head. Results: After one-week, digital subtraction angiography of the femoral head revealed a blood circulation rate of 70 %, and the blood seepage rate of the borehole was 80 %. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling test results showed that necrosis of bone marrow cells in the experimental group was significantly improved compared to that in the control group. Discussion: This study highlights the potential benefits of femoral head intraosseous vascular anastomosis in the treatment of porcine sub-capital femoral neck fractures. Further research and clinical trials are warranted to validate these findings and to explore the translational potential of this technique in human patients.

Recent advances on 3D-bioprinted gelatin methacrylate hydrogels for tissue engineering in wound healing: A review of current applications and future prospects.

Advancements in 3D bioprinting, particularly the use of gelatin methacrylate (GelMA) hydrogels, are ushering in a transformative era in regenerative medicine and tissue engineering. This review highlights the pivotal role of GelMA hydrogels in wound healing and skin regeneration. Its biocompatibility, tunable mechanical properties and support for cellular proliferation make it a promising candidate for bioactive dressings and scaffolds. Challenges remain in optimizing GelMA hydrogels for clinical use, including scalability of 3D bioprinting techniques, durability under physiological conditions and the development of advanced bioinks. The review covers GelMA's applications from enhancing wound dressings, promoting angiogenesis and facilitating tissue regeneration to addressing microbial infections and diabetic wound healing. Preclinical studies underscore GelMA's potential in tissue healing and the need for further research for real-world applications. The future of GelMA hydrogels lies in overcoming these challenges through multidisciplinary collaboration, advancing manufacturing techniques and embracing personalized medicine paradigms.

Bioprinted dermis with human adipose tissue-derived microvascular fragments promotes wound healing.

Tissue-engineered skin is an effective material for treating large skin defects in a clinical setting. However, its use is limited owing to vascular complications. Human adipose tissue-derived microvascular fragments (HaMVFs) are vascularized units that form vascular networks by rapid reassembly. In this study, we designed a vascularized bionic skin tissue using a three-dimensional (3D) bioprinter of HaMVFs and human fibroblasts encapsulated in a hybrid hydrogel composed of GelMA, HAMA, and fibrinogen. Tissues incorporating HaMVFs showed good in vitro vascularization and mechanical properties after UV crosslinking and thrombin exposure. Thus, the tissue could be sutured appropriately to the wound. In vivo, the vascularized 3D bioprinted skin promoted epidermal regeneration, collagen maturation in the dermal tissue, and vascularization of the skin tissue to accelerate wound healing. Overall, vascularized 3D bioprinted skin with HaMVFs is an effective material for treating skin defects and may be clinically applicable to reduce the necrosis rate of skin grafts.

Association between negative parent-related family interactions and child social anxiety: A cross-cultural systematic review and meta-analysis.

This meta-analysis systematically evaluates the strength and direction of the association between negative parent-related family interactions and child social anxiety, and identifies several influencing moderators. Two investigators independently searched international (PsycINFO, PubMed, and Web of Science) and Chinese (CNKI, WanFang, and VIP) databases from their inception dates until March 5, 2023, for suitable articles. Of the 5771 identified records, 85 studies were selected based on inclusion of at least one of the following three dimensions of negative family interactions: insecure attachment (n = 27), parent-related family conflicts (n = 19), or negative parenting styles (n = 46). Meta-analyses showed that all three dimensions were significantly associated with child social anxiety (insecure attachment: r = 0.271, p < 0.0001; parent-related family conflicts: r = 0.226, p < 0.0001; negative parenting styles: r = 0.186, p < 0.0001). For all three dimensions, this association was stronger in children from East Asian culture than in those from European or American culture. In addition, age group, information source, and publication year also significantly moderated this association. Our findings will help guide further research and provide recommendations for the development of effective interventions for reducing social anxiety.

Anatomical characterization of the intraosseous arteries of the porcine tibia.

Introduction: Tibial fractures have a high rate of post-fracture complications. Blood supply is recognized as a positive factor in tibial fracture healing. However, it's difficult to assess blood supply damage after tibial fracture because of the lack of understanding of the tibial intraosseous arteries. This study aimed to delineate and anatomically characterize porcine tibial intraosseous arteries, as a model for the human system. Methods: Twenty right calf specimens with popliteal vessels were prepared from ordinary Landrace pigs. Epoxy resin was perfused into the vasculature from the popliteal artery. After 24 h, casts of the intraosseous arteries of the tibia were exposed through acid and alkali corrosion. The distribution and anatomy of the exposed intraosseous arteries were observed and measured under a microscope, and the data were statistically analyzed. Results: Sixteen complete specimens were obtained. The medullary artery bifurcated into the main ascending and descending branches, which each split into two upward primary branches that further divided into 1-3 secondary branches. Among all specimens, 56 ascending and 42 descending secondary branches, which were all ≥0.3 mm in diameter. Furthermore, the horizontal plane was divided into three zones-safety, buffer, and danger zones-according to the probability of the presence of intraosseous artery. Discussion: The cast perfusion and corrosion approach was successfully applied for anatomical characterization of the intraosseous arteries of the porcine tibia. These observations provide a theoretical basis for understanding the tibial vasculature in humans and will facilitate the establishment of novel "safe corridor" in the tibia for the protection of the blood supply during surgery.

Prognostic implication of heterogeneity and trajectory progression induced by enzalutamide in prostate cancer.

Background: Enzalutamide, as a second-generation endocrine therapy drug for prostate cancer (PCa), is prominent representative among the synthetic androgen receptor antagonists. Currently, there is lack of enzalutamide-induced signature (ENZ-sig) for predicting progression and relapse-free survival (RFS) in PCa. Methods: Enzalutamide-induced candidate markers were derived from single-cell RNA sequencing analysis integrating three enzalutamide-stimulated models (0-, 48-, and 168-h enzalutamide stimulation). ENZ-sig was constructed on the basis of candidate genes that were associated with RFS in The Cancer Genome Atlas leveraging least absolute shrinkage and selection operator method. The ENZ-sig was further validated in GSE70768, GSE94767, E-MTAB-6128, DFKZ, GSE21034, and GSE70769 datasets. Biological enrichment analysis was used to discover the underlying mechanism between high ENZ-sig and low ENZ-sig in single-cell RNA sequencing and bulk RNA sequencing. Results: We identified a heterogenous subgroup that induced by enzalutamide stimulation and found 53 enzalutamide-induced candidate markers that are related to trajectory progression and enzalutamide-stimulated. The candidate genes were further narrowed down into 10 genes that are related to RFS in PCa. A 10-gene prognostic model (ENZ-sig)-IFRD1, COL5A2, TUBA1A, CFAP69, TMEM388, ACPP, MANEA, FOSB, SH3BGRL, and ST7-was constructed for the prediction of RFS in PCa. The effective and robust predictability of ENZ-sig was verified in six independent datasets. Biological enrichment analysis revealed that differentially expressed genes in high ENZ-sig were more activated in cell cycle-related pathway. High-ENZ-sig patients were more sensitive to cell cycle-targeted drugs (MK-1775, AZD7762, and MK-8776) than low-ENZ-sig patients in PCa. Conclusions: Our results provided evidence and insight on the potential utility of ENZ-sig in PCa prognosis and combination therapy strategy of enzalutamide and cell cycle-targeted compounds in treating PCa.

Method for generating transparent porcine tibia showing the intraosseous artery.

BACKGROUND: The occurrence of nonunion after tibial fracture surgery is mainly related to insufficient blood supply. Therefore, anatomical study of the internal and external tibial artery is very important, but there is no good method for displaying the intraosseous artery clearly and intuitively. This hinders the protection and reconstruction of it by surgeons, as well as the development of new instruments and techniques by researchers. OBJECTIVE: To develop a transparent specimen that could clearly display the intraosseous artery of the tibia. METHODS: In 10 isolated pig calves with popliteal vessels, the popliteal artery was exposed and a tube was placed. A casting agent was then injected at constant pressure, and the tissue around the blood vessel was preliminarily removed after solidification. The perivascular tissue and periosteum were further removed via alkali corrosion, and the tibia was fixed with an external fixator to protect the non-corrosive areas at both ends. Alternate acid corrosion and flushing were then applied until the intraosseous artery was completely exposed. The distribution and branches of intraosseous nutrient arteries were observed with the naked eye and via microscopy. Three-dimensional (3D) scanning and 3D printing filling techniques were used to make transparent tibia specimens with preservation of intraosseous arteries. RESULTS: A cast specimen of the intraosseous artery of porcine tibia was successfully generated via epoxy resin perfusion combined with acid-alkali etching, and the intraosseous artery was clearly visible. The 3D printing and filling technique successfully produced a transparent tibia specimen with preservation of internal bone arteries, and accurately restored the external shape of the tibia. The foramen of the nutrient artery appeared near the middle upper third of the lateral edge of the tibia. After entering the tibia, the nutrient artery proceeded forward, medial, and downward for a certain distance, twisted and turned near the midpoint of the medullary cavity, and divided into the ascending and descending branches. After going in the opposite direction for a distance, the ascending trunk sent out 2-3 branches, and the descending trunk sent out 2-3 branches. CONCLUSION: The cast specimen of pig intraosseous artery generated via the above-described perfusion corrosion method provides methodological guidance for the study of anatomical characteristics of the intraosseous artery, and a theoretical basis for the study of new methods of internal fixation and reconstruction of the blood supply of the lower tibia.

Diagnosis and Treatment of Inguinal Hernias after Surgical Treatment of Prostate Cancer, Current State of the Problem.

(1) Purpose: To compare and evaluate the immediate and long-term results of the use of various hernioplasties for the treatment of inguinal hernias after surgical treatment of prostate cancer; to determine the possibility of performing transabdominal preperitoneal (TAPP) hernioplasty and total extraperitoneal (eTEP) hernioplasty in patients with inguinal hernia during surgical treatment of prostate cancer. (2) Method: This study is a clinical analytical prospective study, without the use of randomization. The study included 220 patients with inguinal hernia, who were randomly divided into two groups (group A (n = 100) and group B (n = 120)). Patients in group A received eTEP, and those in group B received TAPP. The end points of the study were the results associated with the operation itself and the prognosis of the disease in the two groups. (3) Results: Group A: five patients had a scrotal hematoma, in 10 cases nosocomial pneumonia or infectious complications from the postoperative wound. The overall rate of early postoperative complications was 15%. In group B, the following postoperative complications were reported: one case of intestinal injury, six cases of acute urinary retention, eight cases of scrotal hematoma and 12 cases of nosocomial pneumonia or infectious complications from the postoperative wound were admitted. The overall incidence of early postoperative complications was 22.5%. There was no statistically significant difference in the incidence of postoperative complications between the two groups (χ2 (3) = 2.54, p > 0.05). (4) Conclusion: During the analysis of the obtained results, no statistically significant difference was found in the duration of hospitalization, the volume of blood loss, the severity of pain syndrome, postoperative complication incidence and recurrence incidence (p > 0.05); however, the comparison groups differed in the duration of the operation: the operation time in group A was much longer compared to group B (p < 0.05).

Construction of a miRNA-Based Nomogram Model to Predict the Prognosis of Endometrial Cancer.

Objective: To investigate the differential expression of microRNA (miRNA) in patients with endometrial cancer and its relationship with prognosis and survival. Method: We used The Cancer Genome Atlas (TCGA) database to analyze differentially expressed miRNAs in endometrial cancer tissues and adjacent normal tissues. In addition, we successfully screened out key microRNAs to build nomogram models for predicting prognosis and we performed survival analysis on the key miRNAs as well. Result: We identified 187 differentially expressed miRNAs, which includes 134 up-regulated miRNAs and 53 down-regulated miRNAs. Further univariate Cox regression analysis screened out 47 significantly differentially expressed miRNAs and selected 12 miRNAs from which the prognostic nomogram model for ECA patients by LASSO analysis was constructed. Survival analysis showed that high expression of hsa-mir-138-2, hsa-mir-548f-1, hsa-mir-934, hsa-mir-940, and hsa-mir-4758 as well as low-expression of hsa-mir-146a, hsa-mir-3170, hsa-mir-3614, hsa-mir-3616, and hsa-mir-4687 are associated with poor prognosis in EC patients. However, significant correlations between the expressions levels of has-mir-876 and hsa-mir-1269a and patients' prognosis are not found. Conclusion: Our study found that 12 significantly differentially expressed miRNAs might promote the proliferation, invasion, and metastasis of cancer cells by regulating the expression of upstream target genes, thereby affecting the prognosis of patients with endometrial cancer.

Recent advances in nanomaterials for prostate cancer detection and diagnosis.

Despite the significant progress in the discovery of biomarkers and the exploitation of technologies for prostate cancer (PCa) detection and diagnosis, the initial screening of these PCa-related biomarkers using current technologies is always demanded with a bioassay or probe with high sensitivity, specificity, and noninvasiveness. Nanomaterials have emerged as novel alternative probes for PCa detection and diagnosis because of their nanoscale size, large ratio of surface area to volume, special surface chemistry, and particularly distinct physical properties. By selecting appropriate nanomaterials, a series of nanosensors or nanoprobes could be constructed for PCa bioassay with high sensitivity, selectivity, and accuracy. Meanwhile, nanosized particles also show significant potential to transport directors or contrast agents to desired sites in vivo for accurate and safe visualization of PCa tissues. Based on these advancements, this review will first outline the recent exploration of PCa biomarkers and the development of technologies for clinical PCa diagnosis. Then, the commonly used nanomaterials for PCa detection and diagnosis will be summarized. Finally, the current challenges and prospects of nanoparticle-based PCa detection and diagnosis methods are also discussed.

Autophagy-Related Long Non-coding RNA Is a Prognostic Indicator for Bladder Cancer.

Bladder cancer (BC) is one of the most common malignant urinary system tumors, and its prognosis is poor. In recent years, autophagy has been closely linked to the development of BC. Therefore, we investigated the potential prognostic role of autophagy-related long non-coding RNA (lncRNA) in patients with BC. We obtained the lncRNA information and autophagy genes, respectively, from The Cancer Genome Atlas (TCGA) data set and the human autophagy database (HADb) and performed a co-expression analysis to identify autophagy gene-associated lncRNAs. Then, we divided the data into training group and testing group. In the training group, 15 autophagy-related lncRNAs were found to have a prognostic value (AC026369.3, USP30-as1, AC007991.2, AC104785.1, AC010503.4, AC037198.1, AC010331.1, AF131215.6, AC084357.2, THUMPD3-AS1, U62317.4, MAN1B1-DTt, AC024060.1, AL662844.4, and AC005229.4). The patients were divided into low-risk group and high-risk group based on the prognostic lncRNAs. The overall survival (OS) time for the high-risk group was shorter than that for the low-risk group [risk ratio (hazard ratio, HR) = 1.08, 95% CI: 1.06-1.10; p < 0.0001]. Using our model, the defined risk value can predict the prognosis of a patient. Next, the model was assessed in the TCGA testing group to further validate these results. A total of 203 patients with BC were recruited to verify the lncRNA characteristics. We divided these patients into high-risk group and low-risk group. The results of testing data set show that the survival time of high-risk patients is shorter than that of low-risk patients. In the training group, the area under the curve (AUC) was more than 0.7, indicating a high level of accuracy. The AUC for a risk model was greater than that for each clinical feature alone, indicating that the risk value of a model was the best indicator for predicting the prognosis. Further training data analysis showed that the gene set was significantly enriched in cancer-related pathways, including actin cytoskeleton regulation and gap junctions. In conclusion, our 15 autophagy-related lncRNAs have a prognostic potential for BC, and may play key roles in the biology of BC.

Canopy photosynthetic capacity drives contrasting age dynamics of resource use efficiencies between mature temperate evergreen and deciduous forests.

Forest resource use efficiencies (RUEs) can vary with tree age, but the nature of these trends and their underlying mechanisms are not well understood. Understanding the age dynamics of forest RUEs and their drivers is vital for assessing the trade-offs between forest functions and resource consumption, making rational management policy, and projecting ecosystem carbon dynamics. Here we used the FLUXNET2015 and AmeriFlux datasets and published literature to explore the age-dependent variability of forest light use efficiency (LUE) and inherent water use efficiency as well as their main regulatory variables in temperate regions. Our results showed that evergreen forest RUEs initially increased before reaching the mature stage (i.e., around 90 years old), and then gradually declined; in contrast, RUEs continuously increased with age for mature deciduous forests. Changing canopy photosynthetic capacity (Amax) was the primary cause of age-related changes in RUEs across temperate forest sites. More importantly, soil nitrogen (N) increased in mature deciduous forests through time but decreased in older evergreen forests. The age-dependent changes in soil N were closely linked with the age dynamics of Amax for mature temperate forests. Additionally, soil nutrient conditions played a greater role in deciduous forest RUEs than evergreen forest RUEs. This study highlights the importance of stand age and forest type on temperate forest RUEs over the long term.

Role of Noncoding RNA in Pulmonary Arterial Hypertension and Potential Drug Therapeutic Target.

Pulmonary arterial hypertension (PAH) is a devastating disease without effective drugs available for its treatment. An in-depth exploration of the pathogenesis of PAH, as well as inquiry into potential therapeutic targets, remains an urgent issue. Non-coding RNAs (ncRNAs) have arisen as key players in malignant tumors, cardiovascular diseases and more recently in PAH progression and development. Network pharmacology is a new discipline based on system biology, which can predict potential therapeutic targets in diseases regulated by multiple genes. In this review, we discuss the current knowledge of ncRNAs and network pharmacology regulated genes involved in PAH, as well as the search for potential drug targets for PAH.