Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: focus on mitochondrial dysfunction.

As a vital component of blood vessels, endothelial cells play a key role in maintaining overall physiological function by residing between circulating blood and semi-solid tissue. Various stress stimuli can induce endothelial injury, leading to the onset of corresponding diseases in the body. In recent years, the importance of mitochondria in vascular endothelial injury has become increasingly apparent. Mitochondria, as the primary site of cellular aerobic respiration and the organelle for "energy information transfer," can detect endothelial cell damage by integrating and receiving various external stress signals. The generation of reactive oxygen species (ROS) and mitochondrial dysfunction often determine the evolution of endothelial cell injury towards necrosis or apoptosis. Therefore, mitochondria are closely associated with endothelial cell function, helping to determine the progression of clinical diseases. This article comprehensively reviews the interconnection and pathogenesis of mitochondrial-induced vascular endothelial cell injury in cardiovascular diseases, renal diseases, pulmonary-related diseases, cerebrovascular diseases, and microvascular diseases associated with diabetes. Corresponding therapeutic approaches are also provided. Additionally, strategies for using clinical drugs to treat vascular endothelial injury-based diseases are discussed, aiming to offer new insights and treatment options for the clinical diagnosis of related vascular injuries.

Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Fabrication of Fe-Zr, Co-Zr, and Ni-Zr Catalysts to Boost CNTs Synthesis from Plastic Wastes and the Electrocatalytic Oxygen Evolution Reaction.

The efficient conversion of plastic wastes to high-value carbon materials like carbon nanotubes (CNTs) is one important issue about the rational recycling, reduction, and reuse of solid wastes. Herein, Fe-, Co-, and Ni-Zr catalysts were prepared and used for CNTs synthesis from polyethylene (PE) waste via a two-stage reaction system. At the same time, the effects of the PE/catalyst ratio and reaction temperature on CNTs synthesis have been studied. Compared with Co-Zr and Ni-Zr, Fe-Zr exhibited the best activity in CNTs synthesis from PE, and it achieved the highest CNTs yield of 806.3 mg/g (per gram of Fe-Zr) at 800 °C with a PE/catalyst ratio of 4. Furthermore, the obtained Fe-Zr/CNTs composite exhibited a low overpotential of 267 mV for the electrocatalytic oxygen evolution reaction (OER) at 20 mA/cm2 in 1 M KOH electrolyte solution, which was 21 mV lower than commercial RuO2 (288 mV) and 50 mV lower than Fe-Zr (317 mV). It was deduced that the in situ growth of CNTs reduced the charge transfer resistance and improved the electron transport efficiency of the Fe-Zr/CNTs composite, leading to superior activity in the electrocatalytic OER. This work provided detailed information for the preparation of the metal/CNTs composite from plastic wastes, which contributed positively to alleviate the environment and energy crisis.

Role of the hydrocarbon molecular structure in CNT growth on Fe-Al catalysts.

Upgrading plastic wastes into high-value products via the thermochemical process is one of the most attractive topics. Although carbon nanotubes (CNTs) have been successfully synthesized from plastic pyrolysis gas over Fe-, Co-, or Ni-based catalysts, a deep discussion about the reaction mechanism was seldom mentioned in the literature. Herein, this work was intended to study the growth mechanism of CNTs from hydrocarbons on Fe-Al2O3 catalysts. C5-C7 hydrocarbons were used to synthesize CNTs in a high-temperature fixed-bed reactor, and the carbon products and cracked gas were analyzed in detail. The CNT yield was in the order of cyclohexane, cyclohexene > n-hexane > n-heptane > n-pentane, 1-hexene. It was proposed that CNT growth on Fe-Al2O3 catalysts was mainly determined by the yield and structure of six-membered cyclic species, which was tailored by the carbon chain length, C-C/CC bonds, and linear/cyclic structures of C5-C7 hydrocarbons. Compared with n-hexane, the six-membered rings of cyclohexane and cyclohexene promoted six-membered cyclic species formation, increasing CNT and benzene yields; the seven-membered carbon chain of n-heptane promoted methyl-six-membered cyclic species formation, decreasing CNT and benzene yields while increasing the toluene yield; the five-membered carbon chain of n-pentane and the CC bond of 1-hexene inhibited six-membered cyclic species formation, decreasing CNT and benzene yields. This work revealed the structure-activity relationship between C5-C7 hydrocarbons and CNT growth, which may direct the process design and optimization of CNT synthesis from plastic pyrolysis gas.

Heterogeneous nuclear ribonucleoprotein A3 controls mitotic progression of neural progenitors via interaction with cohesin.

Cortex development is controlled by temporal patterning of neural progenitor (NP) competence with sequential generation of deep and superficial layer neurons, but underlying mechanisms remain elusive. Here, we report a role for heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in regulating the division of early cortical NPs that mainly give rise to deep-layer neurons via direct neurogenesis. HNRNPA3 is expressed at high levels in NPs of mouse and human cortex at early stages, with a unique peri-chromosome pattern. Intriguingly, downregulation of HNRNPA3 caused chromosome disarrangement, which hindered normal separation of chromosomes during NP division, leading to mitotic delay. Furthermore, HNRNPA3 is associated with the cohesin-core subunit SMC1A and controls its association with chromosomes, implicating a mechanism for the role of HNRNPA3 in regulating chromosome segregation in dividing NPs. Hnrnpa3-deficient mice exhibited reduced cortical thickness, especially of deep layers. Moreover, downregulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a crucial role for HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis.

ColorCells: a database of expression, classification and functions of lncRNAs in single cells.

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.

FAPNET: Feature Fusion with Adaptive Patch for Flood-Water Detection and Monitoring.

In satellite remote sensing applications, waterbody segmentation plays an essential role in mapping and monitoring the dynamics of surface water. Satellite image segmentation-examining a relevant sensor data spectrum and identifying the regions of interests to obtain improved performance-is a fundamental step in satellite data analytics. Satellite image segmentation is challenging for a number of reasons, which include cloud interference, inadequate label data, low lighting and the presence of terrain. In recent years, Convolutional Neural Networks (CNNs), combined with (satellite captured) multispectral image segmentation techniques, have led to promising advances in related research. However, ensuring sufficient image resolution, maintaining class balance to achieve prediction quality and reducing the computational overhead of the deep neural architecture are still open to research due to the sophisticated CNN hierarchical architectures. To address these issues, we propose a number of methods: a multi-channel Data-Fusion Module (DFM), Neural Adaptive Patch (NAP) augmentation algorithm and re-weight class balancing (implemented in our PHR-CB experimental setup). We integrated these techniques into our novel Fusion Adaptive Patch Network (FAPNET). Our dataset is the Sentinel-1 SAR microwave signal, used in the Microsoft Artificial Intelligence for Earth competition, so that we can compare our results with the top scores in the competition. In order to validate our approach, we designed four experimental setups and in each setup, we compared our results with the popular image segmentation models UNET, VNET, DNCNN, UNET++, U2NET, ATTUNET, FPN and LINKNET. The comparisons demonstrate that our PHR-CB setup, with class balance, generates the best performance for all models in general and our FAPNET approach outperforms relative works. FAPNET successfully detected the salient features from the satellite images. FAPNET with a MeanIoU score of 87.06% outperforms the state-of-the-art UNET, which has a score of 79.54%. In addition, FAPNET has a shorter training time than other models, comparable to that of UNET (6.77 min for 5 epochs). Qualitative analysis also reveals that our FAPNET model successfully distinguishes micro waterbodies better than existing models. FAPNET is more robust to low lighting, cloud and weather fluctuations and can also be used in RGB images. Our proposed method is lightweight, computationally inexpensive, robust and simple to deploy in industrial applications. Our research findings show that flood-water mapping is more accurate when using SAR signals than RGB images. Our FAPNET architecture, having less parameters than UNET, can distinguish micro waterbodies accurately with shorter training time.

Smart Sensor-Based Motion Detection System for Hand Movement Training in Open Surgery.

We introduce a smart sensor-based motion detection technique for objective measurement and assessment of surgical dexterity among users at different experience levels. The goal is to allow trainees to evaluate their performance based on a reference model shared through communication technology, e.g., the Internet, without the physical presence of an evaluating surgeon. While in the current implementation we used a Leap Motion Controller to obtain motion data for analysis, our technique can be applied to motion data captured by other smart sensors, e.g., OptiTrack. To differentiate motions captured from different participants, measurement and assessment in our approach are achieved using two strategies: (1) low level descriptive statistical analysis, and (2) Hidden Markov Model (HMM) classification. Based on our surgical knot tying task experiment, we can conclude that finger motions generated from users with different surgical dexterity, e.g., expert and novice performers, display differences in path length, number of movements and task completion time. In order to validate the discriminatory ability of HMM for classifying different movement patterns, a non-surgical task was included in our analysis. Experimental results demonstrate that our approach had 100 % accuracy in discriminating between expert and novice performances. Our proposed motion analysis technique applied to open surgical procedures is a promising step towards the development of objective computer-assisted assessment and training systems.

Ratiometric fluorescent platform for on-site monitoring of sodium pyrosulfite in preserved fruits.

The rapid detection of pyrosulfites in food chemistry is crucial to food safety and health. Here, a coumarin-type ratiometric fluorescent probe was developed based on the Michael addition reaction to detect sodium pyrosulfite (Na2S2O5). The probe exhibited high selectivity and fast response (t1/2 = 6 s) to Na2S2O5 and a low detection limit (26 nM). Because of its excellent ratiometric response performance, the probe was successfully applied to measure the amount of Na2S2O5 in preserved fruits. Colour information analysis and formula calculations were performed to quickly determine the sodium pyrosulfite amount in an actual sample by using a smartphone. Therefore, the intelligent strategy of combining the sensing process and smartphone provides a convenient and efficient method for the fast monitoring of sodium metabisulfite in actual food.

Untypical bilateral breast cancer with peritoneal fibrosis on 18F-FDG PET/CT: case report and literature review.

Background: Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using 18F-FDG PET/CT, providing help for clinical diagnosis and treatment. Case report: A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal 18F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal 18F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant 18F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction. Conclusion: In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.

A novel CpG ODN compound adjuvant enhances immune response to spike subunit vaccines of porcine epidemic diarrhea virus.

CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.

Development of a Novel Peptide-Based PET Tracer [68Ga]Ga-DOTA-BP1 for BCMA Detection in Multiple Myeloma.

B-cell maturation antigen (BCMA) has emerged as a promising tumor marker for the diagnosis and treatment of multiple myeloma. The noninvasive and rapid detection of BCMA expression in vivo provides significant value in screening and evaluating multiple myeloma patients receiving BCMA-targeted therapy. We identified the BCMA-targeting peptide BP1 from a one-bead-one-compound (OBOC) peptide library using a high-throughput microarray strategy. The BCMA-targeting specificity and affinity of BP1 were assessed by surface plasmon resonance imaging (SPRi), flow cytometry, and confocal imaging. BCMA-positive (H929) and BCMA-negative (K562) subcutaneous tumor models were established and labeled with 68Ga for BP1, followed by PET imaging and biodistribution studies. PET imaging demonstrated that 68Ga-labeled BP1 has significant specific uptake in multiple myeloma, enabling rapid identification of BCMA expression and precise delineation of the disease. Thus, BP1 represents an ideal candidate for multiple myeloma imaging.

Gustatory Receptor 206 Participates in the Foraging Behavior of Larvae of Polyphagous Pest Spodoptera litura.

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

Generation of Human Blood Vessel and Vascularized Cerebral Organoids.

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid.

CD146-targeted nuclear medicine imaging in cancer: state of the art.

The transmembrane glycoprotein adhesion molecule CD146 is overexpressed in a wide variety of cancers. Through molecular imaging, a specific biomarker's expression and distribution can be viewed in vivo non-invasively. Radionuclide-labeled monoclonal antibodies or relevant fragments that target CD146 may find potential applications in cancer imaging, thereby offering tremendous value in cancer diagnosis, staging, prognosis evaluation, and prediction of drug resistance. This review discusses the recent developments of CD146-targeted molecular imaging via nuclear medicine, especially in malignant melanoma, brain tumor, lung cancer, liver cancer, breast cancer, and pancreatic cancer. Many studies have proved that CD146 targeting may present a promising strategy for cancer theranostics.

Efficacy of Donepezil Hydrochloride plus Olanzapine for Senile Dementia and Its Effect on the Recovery of Cognitive Function.

Objective: To investigate the efficacy of donepezil hydrochloride plus olanzapine for senile dementia and its effect on the recovery of cognitive function. Methods: A total of 60 patients with senile dementia admitted to our hospital from April 2020 to July 2021 were recruited and assigned to receive either olanzapine alone (observation group) or donepezil hydrochloride plus olanzapine (experimental group) via the random number table method, with 30 patients in each group. Results: The combined therapy resulted in significantly higher clinical efficacy versus monotherapy of olanzapine (P < 0.05). Before treatment, the difference in the scores of cognitive function between the two groups did not come up to the statistical standard (P > 0.05). Donepezil hydrochloride plus olanzapine was associated with significantly higher scores of cognitive function in patients versus olanzapine alone (P < 0.05). The two groups had a similar incidence of adverse reactions (P > 0.05). Conclusion: Donepezil hydrochloride plus olanzapine substantially enhances the recovery of cognitive function of patients with senile dementia and features a manageable safety. Further trials are, however, required prior to clinical promotion.

18F-FDG PET/CT imaging of primary malignant melanoma of rectum with liver metastases mimicking rectum cancer: case report and literature review.

Malignant melanoma (MM) is an aggressive malignant tumor, which mostly occurs on the skin, uvea, etc. The mucosal MM accounts for a small proportion of all MM and can occur in the digestive tract. Primary MM of the digestive tract is rare and can be found in the middle and lower third of the esophagus and the rectum containing melanocytes. Primary rectal MM often occurs in middle-aged and elderly women, with rapid progress and strong invasion. We report a case of a 61-year-old man diagnosed with primary malignant melanoma of the rectum with liver metastases mimicking rectum cancer. 18F-FDG PET/CT showed the rectal wall was markedly thickened with a high metabolic level (SUVmax 10.6) and the boundary between the lesions and the prostate was unclear. In addition, increased FDG uptake were found in multiple lymph nodes, lung, liver, and bones, suggesting metastasis. In this case, 18F-FDG PET/CT shows the advantage of evaluating the whole-body situation and provides valuable information for the diagnosis, tumor stage, evaluation of treatment efficacy, and prognosis of MM.

Generation of vascularized brain organoids to study neurovascular interactions.

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.

Understanding how the organs form and how their cells behave is essential to finding the causes and treatment for developmental disorders, as well as understanding certain diseases. However, studying most organs in live animals or humans is technically difficult, expensive and invasive. To address this issue, scientists have developed models called 'organoids' that recapitulate the development of organs using stem cells in the lab. These models are easier to study and manipulate than the live organs. Brain organoids have been used to recapitulate brain formation as well as developmental, degenerative and psychiatric brain conditions such as microcephaly, autism and Alzheimer's disease. However, these brain organoids lack the vasculature (the network of blood vessels) that supplies a live brain with nutrients and regulates its development, and which has important roles in brain disorders. Partly due to this lack of blood vessels, brain organoids also do not develop a blood brain barrier, the structure that prevents certain contents of the blood, including pathogens, toxins and even certain drugs from entering the brain. These characteristics limit the utility of existing brain organoids. To overcome these limitations, Sun, Ju et al. developed brain organoids and blood vessel organoids independently, and then fused them together to obtain vascularized brain organoids. These fusion organoids developed a robust network of blood vessels that was well integrated with the brain cells, and produced more neural cell precursors than brain organoids that had not been fused. This result is consistent with the idea that blood vessels can regulate brain development. Analyzing the fusion organoids revealed that they contain structures similar to the blood-brain barrier, as well as microglial cells (immune cells specific to the brain). When exposed to lipopolysaccharide ­ a component of the cell wall of certain bacteria ­ these cells responded by initiating an immune response in the fusion organoids. Notably, the microglial cells were also able to engulf connections between brain cells, a process necessary for the brain to develop the correct structures and work normally. Sun, Ju et al. have developed a new organoid system that will be of broad interest to researchers studying interactions between the brain and the circulatory system. The development of brain-blood-barrier-like structures in the fusion organoids could also facilitate the development of drugs that can cross this barrier, making it easier to treat certain conditions that affect the brain. Refining this model to allow the fusion organoids to grow for longer times in the lab, and adding blood flow to the system will be the next steps to establish this system.