Approaches, advantages, and challenges to photon counting detector and multi-energy CT.

Photon counting detector CT (PCD-CT) is the newest major development in CT technology and has been commercially available since 2021. It offers major technological advantages over current standard-of-care energy integrating detector CT (EID-CT) including improved spatial resolution, improved iodine contrast to noise ratio, multi-energy imaging, and reduced noise. This article serves as a foundational basis to the technical approaches and concepts of PCD-CT technology with primary emphasis on detector technology in direct comparison to EID-CT. The article also addresses current technological challenges to PCD-CT with particular attention to cross talk and its causes (e.g., Compton scattering, fluorescence, charge sharing, K-escape) as well as pile-up.

Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

Noise power spectrum (NPS) in computed tomography: Enabling local NPS measurement without stationarity and ergodicity assumptions.

BACKGROUND: Conventional methods for estimating the noise power spectrum (NPS) often necessitate multiple computed tomography (CT) data acquisitions and are required to satisfy stringent stationarity and ergodicity conditions, which prove challenging in CT imaging systems. PURPOSE: The aim was to revisit the conventional NPS estimation method, leading to a new framework that estimates local NPS without relying on stationarity or ergodicity, thus facilitating experimental NPS estimations. METHODS: The scientific foundation of the conventional CT NPS measurement method, based on the Wiener-Khintchine theorem, was reexamined, emphasizing the critical conditions of stationarity and ergodicity. This work proposes an alternative framework, characterized by its independence from stationarity and ergodicity, and its ability to facilitate local NPS estimations. A spatial average of local NPS over a Region of Interest (ROI) yields the conventional NPS for that ROI. The connections and differences between the proposed alternative method and the conventional method are discussed. Experimental studies were conducted to validate the new method. RESULTS: (1) The NPS estimated using the conventional method was demonstrated to correspond to the spatial average of pointwise NPS from the proposed NPS estimation framework. (2) The NPS estimated over an ROI with the conventional method was shown to be the sum of the NPS estimated from the proposed method and a contribution from measurement uncertainty. (3) Local NPS estimations from the proposed method in this work elucidate the impact of surrounding image content on local NPS variations. CONCLUSION: The NPS estimation method proposed in this work allows for the estimation of local NPS without relying on stationarity and ergodicity conditions, offering local NPS estimations with significantly improved precision.

Experimental measurement of local noise power spectrum (NPS) in photon counting detector-CT (PCD-CT) using a single data acquisition.

BACKGROUND: Accurate noise power spectra (NPS) measurement in clinical X-ray CT exams is challenging due to the need for repeated scans, which expose patients to high radiation risks. A reliable method for single CT acquisition NPS estimation is thus highly desirable. PURPOSE: To develop a method for estimating local NPS from a single photon counting detector-CT (PCD-CT) acquisition. METHODS: A novel nearly statistical bias-free estimator was constructed from the raw counts data of PCD-CT scan to estimate the variance of sinogram projection data. An analytical algorithm is employed to reconstruct point-wise covariance cov ( x i , x j ) $\text{cov}({\bf x}_i,{\bf x}_j)$ between any two image pixel/voxel locations x i ${\bf x}_i$ and x j ${\bf x_j}$ . A Fourier transform is applied to obtain the desired point-wise NPS for any chosen location x i ${\bf x}_i$ . The method was validated using experimental data acquired from a benchtop PCD-CT system with various physical phantoms, and the results were compared with the conventional local NPS measurement method using repeated scans and statistical ensemble averaging. RESULTS: The experimental results demonstrate that (1) the proposed method can achieve pointwise/local NPS measurement for a region of interest (ROI) located at any chosen position, accurately characterizing the NPS with spatial structures resulting from image content heterogeneity; (2) the local NPS measured using the proposed method show a higher precision in the measured NPS compared to the conventional measurement method; (3) spatial averaging of the local NPS yields the conventional NPS for a given local ROI. CONCLUSION: A new method was developed to enable local NPS from a single PCD-CT acquisition.

Diagnosis of Canine Tumours and the Value of Combined Detection of VEGF, P53, SF and NLRP3 for the Early Diagnosis of Canine Mammary Carcinoma.

The average life of a dog is generally maintained at ten to fifteen years, and tumours are the predominant reason that leads to the death of dogs, especially canine mammary carcinoma. Therefore, early diagnosis of tumours is very important. In this study, tumor size, morphology, and texture could be seen through general clinical examination, tumor metastasis could be seen through imaging examination, inflammatory reactions could be seen through hematological examination, and abnormal cell morphology could be seen through cytological and histopathological examination. In the 269 malignant cases and 179 benign cases, we randomly selected 30 cases each, and an additional 30 healthy dogs were selected for the experiment (healthy dogs: dogs in good physical condition without any tumor or other diseases). We used RT-qPCR and ELISA to determine the relative expression of vascular endothelial growth factor (VEGF), tumor protein P53 (P53), serum ferritin (SF), and NOD-like receptor protein 3 (NLRP3) in 30 healthy dogs, 30 dogs with benign mammary tumours, and 30 dogs with malignant mammary tumours. In the results, the same expression trend was obtained both in serum and tissues, and the expression of the four markers was the highest in malignant mammary tumours, with highly significant differences compared with the benign and healthy/paracancerous groups. By plotting the ROC curves, it was found that the results of combined tests were better than a single test and the combination of the four markers was the best for the early diagnosis. In conclusion, this can assist the clinical early diagnosis to a certain extent, and also provides some references and assistance for the development of tumor detection kits in clinical practice.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

SIRT3 suppression resulting from the enhanced ß-catenin signaling drives glycolysis and promotes hypoxia-induced cell growth in hepatocellular carcinoma cells.

The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly understood. We assessed sirtuins 3 (SIRT3) levels in HCC tissues and Huh7 cells cultured under hypoxic condition. We investigated the effects of SIRT3 on cell proliferation, glycolytic metabolism, mitochondrial respiration, mitophagy, and mitochondrial biogenesis in Huh7 cells. Besides, we explored the potential mechanisms regulating SIRT3 expression in hypoxically cultured Huh7 cells. Gradual reduction in SIRT3 expressions were observed in both adjacent tumor tissues and tumor tissues. Similarly, SIRT3 expressions were diminished in Huh7 cells cultured under hypoxic condition. Forced expression of SIRT3 attenuated the growth of hypoxically cultured Huh7 cells. SIRT3 overexpression led to a decrease in extracellular acidification rate while increasing oxygen consumption rate. SIRT3 downregulated the levels of hexokinase 2 and pyruvate kinase M2. Moreover, SIRT3 enhanced mitophagy signaling, as indicated by mtKeima, and upregulated key proteins involved in various mitophagic pathways while reducing intracellular reactive oxygen species levels. Furthermore, SIRT3 increased proxisome proliferator-activated receptor-gamma coactivator 1α levels and the amount of mitochondrial DNA in Huh7 cells. Notably, ß-catenin expressions were elevated in Huh7 cells cultured under hypoxic condition. Antagonists and agonists of ß-catenin respectively upregulated and downregulated SIRT3 expressions in hypoxically cultured Huh7 cells. The modulationsof glycolysis and mitochondrial respiration represent the primary mechanism through which SIRT3, suppressed by ß-catenin, inhibits HCC cell proliferation.

Distributed State Estimation for Linear Systems in Networks With Antagonistic Interactions.

This article deals with the distributed state estimation problem for linear systems in networks with cooperative interactions and antagonistic interactions, where the cooperative interactions and the antagonistic interactions are characterized by the positive weights and the negative weights, respectively. Due to the coexistence of the cooperative interactions and the antagonistic interactions, the existing methods based on the non-negatively weighted graph become not applicable. First, a partition method of the nodes and a decomposition form of the system matrices are introduced. Then a new form of distributed observers is proposed in the network with cooperative interactions and antagonistic interactions. Necessary and sufficient conditions, which guarantee the existence of proposed distributed observers, are presented. In particular, when the communication network is cooperative, the proposed method is suitable for two cases, that is, the nodes in each independent strongly connected component are jointly detectable, or each node is jointly detectable with its neighbors. Finally, three examples are simulated to illustrate the effectiveness of the proposed methods.

Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose-induced cardiomyocyte injury.

BACKGROUND: Diabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)-induced cardiomyocyte injury. METHODS: Through GEO database, we obtained rat DCM expression chips and screened differentially expressed genes. Rat cardiomyocytes (H9C2) were induced with HG. 3-hydroxy-3-methylglutarylcoenzyme A synthase 2 (Hmgcs2) and microRNA (miR)-363-5p expression patterns in cells were measured by real-time quantitative polymerase chain reaction or Western blot assay, with the dual-luciferase assay to analyze their binding relationship. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme-linked immunosorbent assay, and various assay kits were applied to evaluate cell viability, cytotoxicity, apoptosis, inflammation responses, and oxidative burden. RESULTS: Hmgcs2 was the vital hub gene in DCM. Hmgcs2 was upregulated in HG-induced cardiomyocytes. Hmgcs2 downregulation increased cell viability, decreased TUNEL-positive cell number, reduced HG-induced inflammation and oxidative stress. miR-363-5p is the upstream miRNA of Hmgcs2. miR-363-5p overexpression attenuated HG-induced cell injury. CONCLUSIONS: Hmgcs2 had the most critical regulatory role in DCM. We for the first time reported that miR-363-5p inhibited Hmgcs2 expression, thereby alleviating HG-induced cardiomyocyte injury.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

A review: analysis of technical challenges in cultured meat production and its commercialization.

The cultured meat technology has developed rapidly in recent years, but there are still many technical challenges that hinder the large-scale production and commercialization of cultured meat. Firstly, it is necessary to lay the foundation for cultured meat production by obtaining seed cells and maintaining stable cell functions. Next, technologies such as bioreactors are used to expand the scale of cell culture, and three-dimensional culture technologies such as scaffold culture or 3D printing are used to construct the three-dimensional structure of cultured meat. At the same time, it can reduce production costs by developing serum-free medium suitable for cultured meat. Finally, the edible quality of cultured meat is improved by evaluating food safety and sensory flavor, and combining ethical and consumer acceptability issues. Therefore, this review fully demonstrates the current development status and existing technical challenges of the cultured meat production technology with regard to the key points described above, in order to provide research ideas for the industrial production of cultured meat.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.

Fuzzy Adaptive Finite-Time Resilient Control Against Unknown False Data Injection Attacks for MIMO Nonlinear Switched Systems With Unknown Dead Zone.

This article studies the finite-time adaptive resilient control problem for MIMO nonlinear switched systems with the unknown dead zone. The sensors of the controlled systems suffer from unknown false data injection (FDI) attacks so that all states cannot be directly applied to the design process of the controller. To address this negative impact of FDI attacks, a new coordinate transformation is designed in control design. Moreover, the Nussbaum gain technique is introduced to deal with the difficulty of unknown time-varying weights caused by FDI attacks. Based on the common Lyapunov function method, a finite-time resilient control algorithm is designed by employing compromised state variables, which ensures that all signals of the closed-loop systems are bounded under arbitrary switching rules even in the presence of unknown FDI attacks. Compared with the existing results, the proposed control algorithm not only enables the controlled systems to reach an equilibrium state in a finite time but also removes the assumption that the sign of the attack weights is positive. In the end, a practical simulation example proves that the designed control method is valid.

Deep-Interior: A new pathway to interior tomographic image reconstruction via a weighted backprojection and deep learning.

BACKGROUND: In recent years, deep learning strategies have been combined with either the filtered backprojection or iterative methods or the direct projection-to-image by deep learning only to reconstruct images. Some of these methods can be applied to address the interior reconstruction problems for centered regions of interest (ROIs) with fixed sizes. Developing a method to enable interior tomography with arbitrarily located ROIs with nearly arbitrary ROI sizes inside a scanning field of view (FOV) remains an open question. PURPOSE: To develop a new pathway to enable interior tomographic reconstruction for arbitrarily located ROIs with arbitrary sizes using a single trained deep neural network model. METHODS: The method consists of two steps. First, an analytical weighted backprojection reconstruction algorithm was developed to perform domain transform from divergent fan-beam projection data to an intermediate image feature space, B ( x ⃗ ) $B(\vec{x})$ , for an arbitrary size ROI at an arbitrary location inside the FOV. Second, a supervised learning technique was developed to train a deep neural network architecture to perform deconvolution to obtain the true image f ( x ⃗ ) $f(\vec{x})$ from the new feature space B ( x ⃗ ) $B(\vec{x})$ . This two-step method is referred to as Deep-Interior for convenience. Both numerical simulations and experimental studies were performed to validate the proposed Deep-Interior method. RESULTS: The results showed that ROIs as small as a diameter of 5 cm could be accurately reconstructed (similarity index 0.985 ± 0.018 on internal testing data and 0.940 ± 0.025 on external testing data) at arbitrary locations within an imaging object covering a wide variety of anatomical structures of different body parts. Besides, ROIs of arbitrary size can be reconstructed by stitching small ROIs without additional training. CONCLUSION: The developed Deep-Interior framework can enable interior tomographic reconstruction from divergent fan-beam projections for short-scan and super-short-scan acquisitions for small ROIs (with a diameter larger than 5 cm) at an arbitrary location inside the scanning FOV with high quantitative reconstruction accuracy.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.

Analgesic Effects of Different Local Infiltration Anesthesia Techniques Combined with Femoral Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Clinical Trial.

Objective: Pain after total knee arthroplasty (TKA) remains an unresolved problem. Femoral nerve block (FNB) could relieve pain; however, it alone is insufficient. The local infiltration anesthesia technique (LIA) has been suggested as a supplement to FNB. This study aimed to evaluate the analgesic effects of different LIA combined with FNB in TKA patients. Methods: The femoral nerve was blocked with 0.375% ropivacaine 20mL, and all patients routinely received general anesthesia. The primary indicator was the proportion of patients who did not receive post-operative remedial analgesia. Seventy-eight patients were randomly assigned to PAI (periarticular injection combined with FNB), IAI (intra-articular injection combined with FNB), or control (FNB alone) groups. All patients underwent FNB under general anesthesia. The primary outcome was the proportion of patients who did not receive additional postoperative analgesia within the first 48 h after surgery. Results: Compared with the PAI and control groups, the IAI group had a higher proportion (69.23%) of patients who did not receive remedial analgesia within 48 hours after surgery (P = 0.009; P = 0.009), a lower consumption of diclofenac sodium lidocaine (P = 0.021; P < 0.001), and an earlier time of walking with a walker (P < 0.001; P < 0.001). The time of first need for remedial analgesia postoperatively in IAI group was longer than the PAI group (P = 0.008) and IAI group has a shorter hospital stay than the control group (P = 0.008). The maximum NRS during the first 48 hours postoperatively and NRS 24 hours after surgery in the IAI group were lower than those in the control and PAI groups. The incidences of POD and PONV were similar among the three groups (P = 0.610; P = 0.264). Conclusion: When combined with FNB, intra-articular injection offers a superior analgesic effect and favorable recovery compared to periarticular injection and separate application of FNB.

Research progress of good markers for canine mammary carcinoma.

PURPOSE: Mammary gland tumors are the most common neoplastic diseases in elderly female dogs, about 50% of which are considered to be malignant. Canine mammary tumors are similar to human breast cancers in many respects, so canine mammary tumors are frequently studied alongside human breast cancer. This article mentioned KI-67, HER-2, COX-2, BRCA1, BRCA2, P53, CA15-3, MicroRNA, Top2α and so on. All these markers are expected to have an important role in the clinic. METHODS: Existing markers of canine mammary carcinoma are reviewed, and the expression of each marker and its diagnostic role for this tumor are described in detail. RESULTS: This article introduced several effective markers of canine mammary tumors, among them, antigen KI-67 (KI-67), human epidermal growth factor receptor 2 (HER-2), cyclooxygenase 2 (COX-2) are promising and can be detected in both serum and tissue samples. Breast cancer caused by mutations in the breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2) is also a hot topic of research. In addition to the above symbols, tumor protein p53 (p53), cancer antigen15-3 (CA15-3), MicroRNA (miRNA), topoisomerase πα (Top2α), proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR) and E-cadherin will also be involved in this paper. We will also mention Mammaglobin, which has been rarely reported so far.

Electronic Flat Band in Distorted Colouring Triangle Lattice.

Dispersionless flat bands (FBs) in momentum space, given rise to electron destructive interference in frustrated lattices, offer opportunities to enhance electronic correlations and host exotic many-body phenomena, such as Wigner crystal, fractional quantum hall state, and superconductivity. Despite successes in theory, great challenges remain in experimentally realizing FBs in frustrated lattices due to thermodynamically structural instability. Here, the observation of electronic FB in a potassium distorted colouring triangle (DCT) lattice is reported, which is supported on a blue phosphorene-gold network. It is verified that the interaction between potassium and the underlayer dominates and stabilizes the frustrated structures. Two-dimensional electron gas is modulated by the DCT lattice, and in turn results in a FB dispersion due to destructive quantum interferences. The FB exhibits suppressed bandwidth with high density of states, which is directly observed by scanning tunneling microscopy and confirmed by the first-principles calculation. This work demonstrates that DCT lattice is a promising platform to study FB physics and explore exotic phenomena of correlation and topological matters.