Current trends and research topics regarding organoids: A bibliometric analysis of global research from 2000 to 2023.

The use of animal models for biological experiments is no longer sufficient for research related to human life and disease. The development of organ tissues has replaced animal models by mimicking the structure, function, development and homeostasis of natural organs. This provides more opportunities to study human diseases such as cancer, infectious diseases and genetic disorders. In this study, bibliometric methods were used to analyze organoid-related articles published over the last 20+ years to identify emerging trends and frontiers in organoid research. A total of 13,143 articles from 4125 institutions in 86 countries or regions were included in the analysis. The number of papers increased steadily over the 20-year period. The United States was the leading country in terms of number of papers and citations. Harvard Medical School had the highest number of papers published. Keyword analysis revealed research trends and focus areas such as organ tissues, stem cells, 3D culture and tissue engineering. In conclusion, this study used bibliometric and visualization methods to explore the field of organoid research and found that organ tissues are receiving increasing attention in areas such as cancer, drug discovery, personalized medicine, genetic disease modelling and gene repair, making them a current research hotspot and a future research trend.

Percutaneous ballon compression for recurrent TN -a retrospective study of 33 cases.

Objective: To investigate the clinical efficacy of percutaneous microballoon compression in the treatment of recurrent TN. Methods: This retrospective study included 33 patients who underwent percutaneous microballoon compression for the treatment of recurrent TN from March 2019 to May 2022. Postoperative pain recurrence and facial numbness were assessed according to the Barrow Neurological Institute (BNI) pain score. Patients' anxiety and sleep status during follow-up were assessed according to the Self-rating Anxiety Scale (SAS) and Pittsburgh Sleep Quality Index (PSQI). Results: All patients (33 cases) were followed up for 12-38 months, with an average follow-up time of 23 months. On postoperative day 1, 31 patients (93.9%) reported no pain, and 2 patients were given drug treatment for pain relief, The total efficacy was 93.9%. Moreover, 2 patients (6.1%) reported significant pain relief 2 weeks postoperatively. There are many complications during and after PBC. The incidence of the trigeminocardiac reflex (TCR) during surgery was 100%, and the incidence of facial numbness, masseter muscle weakness, labial herpes and headache was 97, 60.6, 12.1 and 3%. No patient experienced severe facial numbness, hearing impairment, diplopia, injury to cranial nerves, Meningitis, intracranial haemorrhage or keratitis. 1 patient had recurrence of pain at 6 months post-op, which was relieved by oral medication. 81.8% suffered from anxiety and 54.5% had poor sleep quality before surgery. After the period of PBC, SAS and PSQI scores decreased continuously. There were significant improvements in anxiety and sleep status postoperatively compared with preoperatively. Conclusion: PBC is a safe and effective option for the treatment of recurrent TN. The arduous and demanding nature of the clinical course subjects the patient to severe pain, mental, and physical stress. Thankfully, it significantly improves the symptoms of anxiety, depression, and sleep quality.

Complications analysis of Ilizarov bone transport technique in the treatment of tibial bone defects-a retrospective study of 199 cases.

BACKGROUND: The clinical treatment of long bone defets in the extremities caused by trauma, infection, tumours, and nonunion has been a challenge for orthopaedic surgeons. Bone transport techniques have become the only way to treat such bone defects. However, inevitable difficulties and complications related to bone transport techniques have been reported in many studies. AIM: The purpose of this study was to investigate the risk factors for complications and the effectiveness of the Ilizarov bone transport technique in the treatment of tibial bone defects. METHODS: The study was conducted in 199 patients who underwent treatment with the Ilizarov bone transport technique at our institution from May 2012 to September 2019. Patient demographic data, complications and clinical outcomes after a minimum of 2 years of follow-up were collected and retrospectively analysed. Additionally, a risk factor analysis was performed for the top three major complications. The clinical outcomes were evaluated using the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria at the last clinical follow-up. RESULTS: A total of 199 patients underwent follow-up for 12-40 months, with an average of 23.5 months, and all achieved bone healing. A total of 310 complications occurred, with an average of 1.04 minor complications and 0.48 major complications per patient. The top three complications were pin tract infection in 48 cases (61.3%), axial deviation in 86 cases (43.2%), and delayed union in 50 cases (25.13%). Multivariate analysis showed that the bone defect length (P = 0.02, OR = 5.489), the number of previous surgeries (P = 0.003, OR = 2.204), and the external fixation index (P = 0.01, OR = 1.202) were significantly correlated with pin tract infection. Bone defects of the middle 1/3 (P < 0.001, OR = 23.769), the bone defect length (P < 0.001, OR = 2.776), and the external fixation index (P < 0.001, OR = 1.154) were significantly correlated with axial deviation. The bone defect length (P = 0.003, OR = 1.242), soft tissue defects (P = 0.013, OR = 0.312) and bone defects of the distal 1/3 (P = 0.023, OR = 4.257) were significantly correlated with delayed healing. The ASAMI bone score at the last follow-up showed a rate of excellent and good bone results of 95.48% and a rate of excellent functional results of 87.94%. CONCLUSION: The Ilizarov bone transfer technique is an effective method for treating tibial bone defects, and shortening the treatment period can reduce the incidence of complications. Older patients and those with longer bone defects, a higher external fixation index, more previous operations, and defects of the middle and distal 1/3 had a higher incidence of complications.

Advances in gut microbiome in metabonomics perspective: based on bibliometrics methods and visualization analysis.

Background and aims: Gastrointestinal microbial metabolomics is closely related to the state of the organism and has significant interaction with the pathogenesis of many diseases. Based on the publications in Web of Science Core Collection(WoSCC) from 2004 to 2022, this study conducted a bibliometric analysis of this field, aiming to understand its development trend and frontier, and provide basic information and potential points for in-depth exploration of this field. Methods: All articles on gastrointestinal flora and metabolism published from 2004 to 2022 were collected and identified in WoCSS. CiteSpace v.6.1 and VOSviewer v.1.6.15.0 were used to calculate bibliometric indicators, including number of publications and citations, study categories, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords. A map was drawn to visualize the data based on the analysis results for a more intuitive view. Results: There were 3811 articles in WoSCC that met our criteria. Analysis results show that the number of publications and citations in this field are increasing year by year. China is the country with the highest number of publications and USA owns the highest total link strength and citations. Chinese Acad Sci rank first for the number of institutional publications and total link strength. Journal of Proteome Research has the most publications. Nicholson, Jeremy K. is one of the most important scholars in this field. The most cited reference is "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease". Burst detection indicates that Urine, spectroscopy, metabonomic and gut microflora are long-standing hot topics in this field, while autism spectrum disorder and omics are likely to be at the forefront of research. The study of related metabolic small molecules and the application of gastrointestinal microbiome metabolomics in various diseases are currently emerging research directions and frontier in this field. Conclusion: This study is the first to make a bibliometric analysis of the studies related to gastrointestinal microbial metabolomics and reveal the development trends and current research hotspots in this field. This can contribute to the development of the field by providing relevant scholars with valuable and effective information about the current state of the field.

Upregulation of TMEM40 is associated with the malignant behavior and promotes tumor progression in cervical cancer.

OBJECTIVE: Recent studies indicated that transmembrane protein 40 (TMEM40) is associated with several types of cancers but is not clear in cervical cancer (CC). The study aimed to examine the role of TMEM40 in CC and related mechanisms. METHODS: The expression of TMEM40 in CC tissues and cell lines was studied with western blot and real-time quantitative RT-PCR. The effect of TMEM40 on proliferation was evaluated by CCK-8, EdU and colony formation assay. The migration, invasion, cell cycle and apoptosis of CC cells were studied with wound healing, transwell assays and flow cytometry. Tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model. RESULTS: The results revealed that the TMEM40 elevation in CC tissues and cell lines was closely correlated with tumor size and lymph node metastasis in clinical patients. Upregulation of TMEM40 with OE-TMEM40 vector promoted the invasion, migration and proliferation, inhibited the apoptosis and led to distinct S cell cycle arrest in CC cell lines. Silencing TMEM40 with shRNA inhibited the invasion, migration and proliferation, promoted apoptosis and led to a G0/G1 cell cycle arrest in CC cell lines. Silence of TMEM40 downregulated the expression of c-MYC, Cyclin D1, matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), but in contrast, activated p53 and several apoptosis related proteins such as p53, Caspase-3, Caspase-9 and PARP1. In addition, TMEM40 silencing dramatically decreased tumor growth in mice models. CONCLUSION: The present study demonstrates that TMEM40 upregulation can be a potential prognostic biomarker and contribute to CC development.

Adaptive temporal patterns of echolocation and flight behaviors used to fly through varied-sized windows by 2 species of high duty cycle bats.

As actively sensing animals guided by acoustic information, echolocating bats must adapt their vocal-motor behavior to various environments and behavioral tasks. Here, we investigated how the temporal patterns of echolocation and flight behavior were adjusted in 2 species of bats with a high duty cycle (HDC) call structure, Rhinolophus ferrumequinum and Hipposideros armiger, when they flew along a straight corridor and then passed through windows of 3 different sizes. We also tested whether divergence existed in the adaptations of the 2 species. Both H. armiger and R. ferrumequinum increased their call rates by shortening the pulse duration and inter-pulse interval for more rapid spatial sampling of the environment when flying through smaller windows. Bats produced more sonar sound groups (SSGs) while maintaining a stable proportion of calls that made up SSGs during approaches to smaller windows. The 2 species showed divergent adjustment in flight behavior across 3 different window sizes. Hipposideros armiger reduced its flight speed to pass through smaller windows while R. ferrumequinum increased its flight speed. Our results suggest that these 2 species of HDC bats adopt similar acoustic timing patterns for different tasks although they performed different flight behaviors.

Experimental Research on the Preparation of K2CO3/Expanded Vermiculite Composite Energy Storage Material.

Thermochemical adsorption energy storage is a potential energy utilization technology. Among these technologies, the composite energy storage material prepared by K2CO3 and expanded vermiculite (EVM) shows excellent performance. In this paper, the influence of the preparation process using the impregnation method and vacuum impregnation method on K2CO3/EVM composite material is studied. The preparation plan is further optimized with the solution concentration and the expanded vermiculite particle size as variables. In the experiment, mercury intrusion porosimetry (MIP) is used to measure the porosity and other parameters. Additionally, with the help of scanning electron microscopy (SEM), the morphological characteristics of the materials are obtained from a microscopic point of view. The effects of different preparation parameters are evaluated by comparing the experimental results. The results show that the K2CO3 specific gravity of the composite material increases with the increase of the vacuum degree, up to 70.440 wt.% (the vacuum degree is 6.7 kPa). Expanded vermiculite with a large particle size (3~6 mm) can carry more K2CO3, and content per cubic centimeter of K2CO3 can be as high as 0.466 g.

Furin Enzyme and pH Synergistically Triggered Aggregation of Gold Nanoparticles for Activated Photoacoustic Imaging and Photothermal Therapy of Tumors.

Specific and effective accumulation of nanoparticles within tumors is highly crucial for precise cancer diagnosis and treatment. Therefore, spatiotemporally manipulating the aggregation of small gold nanoparticles (AuNPs) in a tumor microenvironment is of great significance for enhancing the diagnostic and therapeutic efficacy of tumors. Herein, we reported a novel furin enzyme/acidic pH synergistically triggered small AuNP aggregation strategy for activating the photoacoustic (PA) imaging and photothermal (PTT) functions of AuNPs in vivo. Smart gold nanoparticles decorated with furin-cleavable RVRR (Arg-Val-Arg-Arg) peptides (Au-RRVR) were rationally designed and fabricated. Both in vitro and in vivo experiments demonstrated that such Au-RRVR nanoparticles could be simultaneously induced by furin and acidic pH to form large aggregates within tumorous tissue resulting in improved tumor accumulation and retention, which can further activate the PA and PTT effect of AuNPs for sensitive imaging and efficient therapy of tumors. Thus, we believe that this dual-stimuli-responsive aggregation system may offer a universal platform for effective cancer diagnosis and treatment.

Social calls influence the foraging behavior in wild big-footed myotis.

BACKGROUND: Why a variety of social animals emit foraging-associated calls during group foraging remains an open question. These vocalizations may be used to recruit conspecifics to food patches (i.e. food advertisement hypothesis) or defend food resources against competitors (food defence hypothesis), presumably depending on food availability. Insectivorous bats rely heavily on vocalizations for navigation, foraging, and social interactions. In this study, we used free-ranging big-footed myotis (Myotis macrodactylus Temminck, 1840) to test whether social calls produced in a foraging context serve to advertise food patches or to ward off food competitors. Using a combination of acoustic recordings, playback experiments with adult females and dietary monitoring (light trapping and DNA metabarcoding techniques), we investigated the relationship between insect availability and social vocalizations in foraging bats. RESULTS: The big-footed myotis uttered low-frequency social calls composed of 7 syllable types during foraging interactions. Although the dietary composition of bats varied across different sampling periods, Diptera, Lepidoptera, and Trichoptera were the most common prey consumed. The number of social vocalizations was primarily predicted by insect abundance, insect species composition, and echolocation vocalizations from conspecifics. The number of conspecific echolocation pulses tended to decrease following the emission of most social calls. Feeding bats consistently decreased foraging attempts and food consumption during playbacks of social calls with distinctive structures compared to control trials. The duration of flight decreased 1.29-1.96 fold in the presence of social calls versus controls. CONCLUSIONS: These results support the food defence hypothesis, suggesting that foraging bats employ social calls to engage in intraspecific food competition. This study provides correlative evidence for the role of insect abundance and diversity in influencing the emission of social calls in insectivorous bats. Our findings add to the current knowledge of the function of social calls in echolocating bats.

Protein sulfenic acid-mediated anchoring of gold nanoparticles for enhanced CT imaging and radiotherapy of tumors in vivo.

Radiotherapy (RT) has become one of the most widely used treatments for malignant tumors in clinics. Developing a novel radiosensitizer for the integration of precise diagnosis and effective radiotherapy against hypoxic tumors is desirable but remains a great challenge. Herein, protein sulfenic acid reactive gold nanoparticles as effective radiosensitizers were for the first time reported for enhanced X-ray computed tomography (CT) imaging and radiotherapy of tumors in vivo. The gold nanoparticles were decorated with biocompatible poly(ethylene glycol), folic acid (FA), and sulfenic acid reactive groups 1,3-cyclohexanedione (CHD). Such a nanostructure enables on-site immobilization within tumors under oxidative stress through the specific reaction between CHD and endogenous protein sulfenic acids resulting in enhanced accumulation and retention of gold nanoparticles within tumors, which remarkably improves the sensitivity of CT imaging and the radiotherapeutic efficacy of tumors in living mice. This study thus is the first to demonstrate that protein sulfenic acid reactive gold nanoparticles with a tumor anchoring function may serve as effective radiosensitizers for clinical X-ray theranostic application in the future.

Sulfenic Acid-Mediated on-Site-Specific Immobilization of Mitochondrial-Targeted NIR Fluorescent Probe for Prolonged Tumor Imaging.

Mitochondria plays pivotal roles in energy production and apoptotic pathways. Mitochondria-targeting strategy has been recognized as a promising way for cancer theranostics. Thus, spatiotemporally manipulating the prolonged retention of theranostic agents within mitochondria is considerably significant in cancer diagnosis and therapy. Herein, as a proof-of concept, we for the first time report a sulfenic acid-responsive platform on controlled immobilization of probes within mitochondria for prolonged tumor imaging. A novel near-infrared (NIR) probe DATC constructed with a NIR dye (Cy5) as signal unit, a cationic triphenylphosphonium (TPP) for mitochondria targeting, and a sulfenic acid-reactive group (1,3-cyclohexanedione) for mitochondrial fixation was rationally designed and synthesized. This probe displayed good target ability to mitochondria and could act as a promising fluorescent probe for specific visualization of endogenous protein sulfenic acids expressed in the mitochondria. Moreover, the probe could be spontaneously fixed on site through the specific reaction and covalent binding to the sulfenic acids of oxidized proteins under oxidative stress, resulting in enhanced intracellular uptake and prolonged retention. We thus believe that this mitochondria-targeted and locational immobilization strategy may offer a new insight for long-term tumor imaging and effective therapy.

A novel αvß3 integrin-targeted NIR-II nanoprobe for multimodal imaging-guided photothermal therapy of tumors in vivo.

Developing novel small-molecule-based probes with both deep tissue imaging and therapeutic functions is highly significant in cancer diagnosis and treatment. Herein, we report a novel second near-infrared (NIR-II) fluorescent probe QT-RGD constructed with a NIR-II emissive organic fluorophore and two cyclic-(arginine-glycine-aspartic acid) (cRGD) peptides that can specifically bind to the tumor-associated αvß3 integrin for accurate tumor diagnosis and targeting therapy. The isotopic 125I-labeled probe exhibited great tumor targeting ability and emitted intensive NIR-II/photoacoustic (PA)/single-photon emission computed tomography (SPECT) signals, which allows specific and sensitive multimodal visualization of tumors in vivo. More notably, this probe could also be applied for effective imaging-guided photothermal therapy (PTT) of tumors in mouse models owing to its prominent photothermal conversion efficiency and excellent photothermal stability. We thus envision that our work which unveils a combination of NIR-II/PA/SPECT imaging and PTT would offer a valuable means of improving tumor diagnostic accuracy as well as therapeutic efficacy.

Light-triggered crosslinking of gold nanoparticles for remarkably improved radiation therapy and computed tomography imaging of tumors.

Aim: We aimed to characterize the tumor-targeting and radiosensitization properties of the photo-responsive gold nanoparticles (AuNPs) decorated photolabile diazirine group and folic acid for improved radiotherapy and computed tomography imaging of tumors. Methods: Folic acid and photolabile diazirine group were covalently conjugated on the surface of AuNPs to afford the desired photo-responsive dAuNP-FA (AuNPs capped with poly(ethylene) glycol ligands bearing photolabile diazirine group and folic acid). The probes were intravenously injected into tumor-bearing mice followed by photocrosslinking upon 405 nm laser irradiation for radiotherapy and computed tomography imaging of tumors in vivo. Results: Light-triggered crosslinking of AuNPs in vivo remarkably enhanced the accumulation and retention of AuNPs within tumors. Conclusion: We have successfully developed a novel photo-responsive Au particle-based tumor theranostic probe showing remarkably improved tumor targeting ability and radiosensitization effect.

A light-up near-infrared probe with aggregation-induced emission characteristics for highly sensitive detection of alkaline phosphatase.

Developing activatable near-infrared (NIR) probes to specifically monitor and visualize the activities of cancer-related enzymes is highly significant yet challenging in early cancer diagnosis. Taking advantage of the unique photophysical characteristics of aggregation-induced emission (AIE) fluorophores, here we design and synthesize a novel activatable probe QMTP by conjugating an AIE fluorophore quinolone-malononitrile to a hydrophilic phosphate-modified phenol group. The probe was initially non-fluorescent in aqueous solution due to its good water solubility, but was readily activated to generate a strong NIR fluorescence upon treatment with alkaline phosphatase (ALP), which enables specific detection of ALP activity. Furthermore, we have employed QMTP to monitor and spatially map the activity of endogenous ALP both in cancer cells and in drug-treated zebrafish larvae. The experimental results reveal that the QMTP probe has great specificity and sensitivity for ALP detection. We thus believe that our work offers a promising tool for accurate detection of ALP-associated diseases in preclinical applications.

Rational Design and Synthesis of a Metalloproteinase-Activatable Probe for Dual-Modality Imaging of Metastatic Lymph Nodes in Vivo.

Lymphatic metastasis is an important prognostic indicator for cancer progression. It is therefore considerably meaningful to develop molecularly targeted imaging probes for noninvasive and accurate identification of metastatic lymph nodes (MLNs) at early stages of tumor metastasis. Herein, we report a novel matrix metalloproteinase-2 (MMP-2)-activatable probe constructed with a near-infrared dye (Cy5), a quencher (QSY21), and a tumor-targeting peptide cRGD covalently linked through a radionuclide (125I)-labeled peptide substrate for accurate detection of MLNs. Upon cleavage with activated MMP-2, the above probe emitted MMP-2 concentration-dependent near-infrared fluorescence, which allows sensitive and specific visualization of MLNs via both optical and single-photon emission computed tomography imaging techniques. We thus envision that this probe would serve as a useful tool for studying tumor-induced lymphangiogenesis.

Light-Triggered Covalent Coupling of Gold Nanoparticles for Photothermal Cancer Therapy.

Manipulating the cross-coupling of gold nanoparticles (AuNPs) to maximize the photothermal effect is a promising strategy for cancer therapy. Here, by taking advantage of the well-known tetrazole/alkene photoclick chemistry, we have demonstrated for the first time that small AuNPs (23 nm) decorated with both 2,5-diphenyltetrazole and methacrylic acid on their surfaces can form covalently crosslinked aggregates upon laser irradiation (λ=405 nm). In vitro studies indicated that the light-triggered assembling shifted the surface plasmon resonance of AuNPs significantly to near-infrared (NIR) regions, which as a consequence effectively enhanced the efficacy of photothermal therapy for 4T1 breast cancer cells. We thus believe that this new light-triggered cross-coupling approach might offer a valuable tool for cancer treatment.

An acidic pH/reduction dual-stimuli responsive nanoprobe for enhanced CT imaging of tumours in vivo.

Computed tomography (CT) is one of the most frequently used diagnostic imaging modalities in clinics. However, the fast clearance of CT contrast agents through the kidney and short circulation time severely restrict their in vivo applications. Herein, taking advantage of the biocompatible CBT condensation reaction, we rationally designed and synthesized a new smart acidic pH/glutathione (GSH) dual-stimuli responsive nanoprobe (1) which can intermolecularly undergo condensation and form a nanoparticle assembly (I-NPs) in the tumour microenvironment. In vivo CT imaging results indicated that probe 1 could be successfully applied for enhanced CT imaging of tumours in nude mice with a low dose of 21.79 mg I per kg body weight, which may offer a promising tool for precise tumor diagnosis.