Global research hotspots, development trends and prospect discoveries of phase separation in cancer: a decade-long informatics investigation.

Liquid-liquid phase separation (LLPS) is a complex and subtle phenomenon whose formation and regulation take essential roles in cancer initiation, growth, progression, invasion, and metastasis. This domain holds a wealth of underutilized unstructured data that needs further excavation for potentially valuable information. Therefore, we retrospectively analyzed the global scientific knowledge in the field over the last decade by using informatics methods (such as hierarchical clustering, regression statistics, hotspot burst, and Walktrap algorithm analysis). Over the past decade, this area enjoyed a favorable development trend (Annual Growth Rate: 34.98%) and global collaboration (International Co-authorship: 27.31%). Through unsupervised hierarchical clustering based on machine learning, the global research hotspots were divided into five dominant research clusters: Cluster 1 (Effects and Mechanisms of Phase Separation in Drug Delivery), Cluster 2 (Phase Separation in Gene Expression Regulation), Cluster 3 (Phase Separation in RNA-Protein Interaction), Cluster 4 (Reference Value of Phase Separation in Neurodegenerative Diseases for Cancer Research), and Cluster 5 (Roles and Mechanisms of Phase Separation). And further time-series analysis revealed that Cluster 5 is the emerging research cluster. In addition, results from the regression curve and hotspot burst analysis point in unison to super-enhancer (a=0.5515, R2=0.6586, p=0.0044) and stress granule (a=0.8000, R2=0.6000, p=0.0085) as the most potential star molecule in this field. More interestingly, the Random-Walk-Strategy-based Walktrap algorithm further revealed that "phase separation, cancer, transcription, super-enhancer, epigenetics"(Relevance Percentage[RP]=100%, Development Percentage[DP]=29.2%), "stress granule, immunotherapy, tumor microenvironment, RNA binding protein"(RP=79.2%, DP=33.3%) and "nanoparticle, apoptosis"(RP=70.8%, DP=25.0%) are closely associated with this field, but are still under-developed and worthy of further exploration. In conclusion, this study profiled the global scientific landscape, discovered a crucial emerging research cluster, identified several pivotal research molecules, and predicted several crucial but still under-developed directions that deserve further research, providing an important reference value for subsequent basic and clinical research of phase separation in cancer.

Comparative investigation of neoadjuvant immunotherapy versus adjuvant immunotherapy in perioperative patients with cancer: a global-scale, cross-sectional, large-sample informatics study.

BACKGROUND: Neoadjuvant and adjuvant immunotherapies for cancer have evolved through a series of remarkable and critical research advances; however, addressing their similarities and differences is imperative in clinical practice. Therefore, this study aimed to examine their similarities and differences from the perspective of informatics analysis. METHODS: This cross-sectional study retrospectively analyzed extensive relevant studies published between 2014 and 2023 using stringent search criteria, excluding non-peer-reviewed and non-English documents. The main outcome variables are publication volume, citation volume, connection strength, occurrence frequency, relevance percentage, and development percentage. Furthermore, an integrated comparative analysis was conducted using unsupervised hierarchical clustering, spatiotemporal analysis, regression statistics, and Walktrap algorithm analysis. RESULTS: This analysis included 1,373 relevant studies. Advancements in neoadjuvant and adjuvant immunotherapies have been promising over the last decade, with an annual growth rate of 25.18% vs. 6.52% and global collaboration (International Co-authorships) of 19.93% vs. 19.84%. Respectively, five dominant research clusters were identified through unsupervised hierarchical clustering based on machine learning, among which Cluster 4 (Balance of neoadjuvant immunotherapy efficacy and safety) and Cluster 2 (Adjuvant immunotherapy clinical trials) (Average Publication Year [APY]: 2021.70±0.70 vs. 2017.54±4.59) are emerging research populations. Burst and regression curve analyses uncovered domain pivotal research signatures, including microsatellite instability (R2=0.7500, P=0.0025) and biomarkers (R2=0.6505, P=0.0086) in neoadjuvant scenarios, and the tumor microenvironment (R2=0.5571, P=0.0209) in adjuvant scenarios. The Walktrap algorithm further revealed that "neoadjuvant immunotherapy, non-small cell lung cancer (NSCLC), immune checkpoint inhibitors, melanoma" and "adjuvant immunotherapy, melanoma, hepatocellular carcinoma, dendritic cells" (Relevance Percentage: 100% vs. 100%, Development Percentage: 37.5% vs. 17.1%) are extremely relevant to this field but remain underdeveloped, highlighting the need for further investigation. CONCLUSION: This study identified pivotal research signatures and provided substantial predictions for neoadjuvant and adjuvant cancer immunotherapies. In addition, comprehensive quantitative comparisons revealed a notable shift in focus within this field, with neoadjuvant immunotherapy taking precedence over adjuvant immunotherapy after 2020; such a qualitative finding facilitate proper decision-making for subsequent research and mitigate the wastage of healthcare resources.

Anion Photoelectron Spectroscopy and Quantum Chemistry Calculations of Gas-Phase TaSi17Ì and TaSi18Ì Clusters: Structural Determination, Bonding Characteristics, and Multiplicity of Structural Forms.

This study explores the structures and chemical bonding properties of TaSi17̅ and TaSi18̅ clusters by employing anion photoelectron spectroscopy and theoretical computations. Utilizing CALYPSO and ABCluster programs for initial structure prediction, B3LYP hybrid functional for optimization, and CCSD(T)/def2-TZVPPD level for energy calculations, the research identifies the most stable isomers of these clusters. Key findings include the identification of two coexisting low-energy isomers for TaSi17̅, exhibiting Ta-endohedral fullerene-like cage structures, and the lowest-energy structures of TaSi17̅ and TaSi18̅ anions can be considered as derived from the TaSi16̅ superatom cluster. The study enhances the understanding of group 14 element chemistry and guides the design of novel inorganic metallic compounds, potentially impacting materials science.

The role of CEMIP in cancers and its transcriptional and post-transcriptional regulation.

CEMIP is a protein known for inducing cell migration and binding to hyaluronic acid. Functioning as a hyaluronidase, CEMIP primarily facilitates the breakdown of the extracellular matrix component, hyaluronic acid, thereby regulating various signaling pathways. Recent evidence has highlighted the significant role of CEMIP in different cancers, associating it with diverse pathological states. While identified as a biomarker for several diseases, CEMIP's mechanism in cancer seems distinct. Accumulating data suggests that CEMIP expression is triggered by chemical modifications to itself and other influencing factors. Transcriptionally, chemical alterations to the CEMIP promoter and involvement of transcription factors such as AP-1, HIF, and NF-κB regulate CEMIP levels. Similarly, specific miRNAs have been found to post-transcriptionally regulate CEMIP. This review provides a comprehensive summary of CEMIP's role in various cancers and explores how both transcriptional and post-transcriptional mechanisms control its expression.

All-in-one detection of breast cancer-derived exosomal miRNA on a pen-based paper chip.

Exosomal microRNAs (miRNAs) play a pivotal role in intercellular communication, regulating gene expression in target cells, and hold significant promise as cancer biomarkers for early detection and screening. However, achieving precise and viable detection of exosomal miRNAs remains a challenge. This paper proposes an all-in-one detection strategy for breast cancer-derived exosomal miRNA-21 on a pen-based paper chip (PPC). The PPC is constructed using a modified automatic pen and lateral flow assay (LFA), which results in a cost-effective fabrication process. The user only needs to add the sample and trigger the top of the self-contained PPC after a period of time to complete the entire detection process. To enhance the sensitivity of exosomal miRNA testing, an enzyme-free catalyzed hairpin assembly (CHA) is further introduced, enabling highly sensitive detection of miRNA-21 with a limit of detection (LOD) of 25 fmol. Additionally, the detection of miRNAs in differentially-expressed cells and clinical samples has also been successfully achieved with high specificity. Overall, the proposed PPC provides an effective tool for detecting early cancer, monitoring diseases, and establishing point of care testing (POCT).

Long-term effects of vaginal surgery and endogenous ovarian hormones on the vagina and bladder.

Background: Surgery is a common treatment for pelvic organ prolapse (POP); however, risk of recurrence and reoperation is high, resulting in a negative impact on quality of life and sexual function. Aim: To examine the long-term effects of POP surgery and endogenous circulating ovarian hormones on the vagina and bladder. Methods: Our animal model simulated surgical injury of the vagina and bladder during POP surgery. Female Rowett nude rats were divided into 4 groups: intact control (IC), vaginal surgery only (V), ovariectomy only (O), and ovariectomy + vaginal surgery (OV). Rats were euthanized 10 weeks postsurgery. Proximal vagina and bladder dome/trigone underwent (1) organ bath myography to assess smooth muscle contractility; (2) real-time quantitative polymerase chain reaction to quantify mRNA expression of elastin, collagen I and III, and PGP9.5 (protein gene product 9.5); (3) enzyme-linked immunosorbent assay for protein quantification of elastin and collagen I and III; and (4) hematoxylin-eosin/immunohistochemistry staining. Outcomes: The primary outcome was tissue contractility as measured by organ bath myography. Secondary outcomes included gene and protein expression of collagen I and III and elastin. Results: O and OV showed reduced vaginal wall contractility vs IC and V (P < .002). Bladder dome and trigone displayed different contractile patterns, with significant differences between O and OV (P < .05), suggesting a negative effect from surgery rather than ovariectomy. OV demonstrated consistent reductions in contractility and elastin/collagen protein expression for the vagina and bladder vs IC. V had similar contractility and increased collagen I expression vs IC, suggesting a protective effect of ovarian hormones. Vaginal epithelium thinning was confirmed in the ovariectomized groups (P = .001), although there was no statistical significance in muscularis thinning with surgery or ovariectomy. O, V, and OV showed significant downregulation of PGP9.5 mRNA expression vs IC. Clinical Translation: These data allow researchers to gain insights into the long-term effects of surgery and deprivation of ovarian hormones. Future studies can use this animal model to investigate other mechanisms that may affect long-term tissue changes due to surgical intervention. Strengths and Limitations: Major strengths are long-term data on the effects of POP surgery and development of an animal model for future studies. However, the animal model limits our ability to extrapolate to humans, where tissue healing is modulated by many factors. Conclusion: Our animal model provides evidence that ovarian hormone deprivation and POP surgery result in negative long-term effects on tissue function and extracellular matrix.

Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway.

Background: Ligustilide (LIG) and n-butylphthalide (NBP) have neuroprotective effects in cerebral ischemia; however, their roles in gliomas are not well-known.This study aimed to explore the anti-glioma effects of LIG and NBP individually and the synergistic effects of temozolomide (TMZ) via the PI3K/Akt Signaling Pathway. Materials and Methods: Cytotoxicity of LIG and NBP alone and in combination with TMZ in U251 cells was determined using the CCk-8. The effect of compounds alone or in combination on cell migration was detected using the wound healing assay, and the invasion was evaluated by transwell assays, respectively. Cell apoptosis was quantified by flow cytometry and the changed expressions of proteins were detected by Western blotting. Results: The results showed that LIG and NBP significantly inhibited the growth of U251 cells at concentrations of 4-10 µg/mL and 1.5-6 µg/mL in a dose-dependent manner (p<0.05, p<0.01). The combination of 20 µg/mL TMZ with LIG in the concentration range of 4-10 µg/mL or with NBP of 0.5-6 µg/mlachieved synergistic effect towardsU251 cells. LIG and NBP, alone or in combination with TMZ, markedly inhibited cell invasion (p< 0.001) and enhanced apoptosis (p< 0.05). The combination of TMZ with LIG or NBP markedly inhibited cell migration (p< 0.001). Western blot analysis showed that LIG, NBP, and TMZ, alone and in combination, significantly decreased the expression of Bcl-2, p-PI3K, and p-Akt, and increased the expression of Bax. Conclusion: Both LIG and NBP exert anti-glioma effects on their own through the PI3K/Akt pathway and enhance TMZ-mediated anti-glioma efficiency via the same pathway.

Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury.

Spinal cord injury (SCI) is a traumatic condition of the central nervous system that causes paralysis of the limbs. Micro electric fields (EF) have been implicated in a novel therapeutic approach for nerve injury repair and regeneration, but the effects of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles that are induced by micro electric fields (EF-sEVs) stimulation on SCI remain unknown. The aim of the present study was to investigate whether EF-sEVs have therapeutic effects a rat model of SCI. EF-sEVs and normally conditioned human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (CON-sEVs) were collected and injected intralesionally into SCI model rats to evaluate the therapeutic effects. We detect the expression of candidate long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in EF-sEVs and CON-sEVs. The targets and downstream effectors of lncRNA-MALAT1 were investigated using luciferase reporter assays. Using both in vivo and in vitro experiments, we demonstrated that EF-sEVs increased autophagy and decreased apoptosis after SCI, which promoted the recovery of motor function. We further confirmed that the neuroprotective effects of EF-sEVs in vitro and in vivo correlated with the presence of encapsulated lncRNA-MALAT1 in sEVs. lncRNA-MALAT1 targeted miR-22-3p via sponging, reducing miR-22-3p's suppressive effects on its target, SIRT1, and this translated into AMPK phosphorylation and increased levels of the antiapoptotic protein Bcl-2. Collectively, the present study identified that the lncRNA-MALAT1 in EF-sEVs plays a neuroprotective role via the miRNA-22-3p/SIRT1/AMPK axis and offers a fresh perspective and a potential therapeutic approach using sEVs to improve SCI.

Structural Determination and Bonding Characteristics of the Gas-Phase Ta2Si2Ì Anion and Its Neutral: Anion Photoelectron Spectroscopy and Theoretical Studies.

The structures and bonding characteristics of Ta2Si2̅/0 clusters are investigated using anion photoelectron spectroscopy and quantum chemical calculations. The vertical detachment energy of the Ta2Si2̅ anion is measured to be 2.00 ± 0.08 eV using the 266 nm photon. It is found that the Ta2Si2̅ anion has three low-energy isomers with a C2v symmetric Ta-Ta dibridged structural framework, all of which contribute to the experimental photoelectron spectrum, while the Ta2Si2 neutral also has a C2v symmetric Ta-Ta dibridged structural framework. The charge-transfer from Ta atoms to Si atoms is discovered using atomic dipole moment corrected Hirshfeld analysis for the Ta2Si2̅ anion and Ta2Si2 neutral. Chemical bonding investigations show that both the Ta2Si2̅ anion and Ta2Si2 neutral have a strong covalent Ta-Ta bond, as well as σ and π double bonding patterns. Furthermore, the Ta atoms are linked together by a single 2c-2e Ta2 σ bond, whereas the Si atoms are linked together with the Ta atoms via four 2c-2e TaSi σ bonds, two 3c-2e TaSi2 σ bonds, one 4c-2e Ta2Si2 σ bond, and one 4c-2e Ta2Si2 π bond.

Numerical simulation study of steel wire winding split ultra-high pressure die.

In this paper, a new type of large-cavity two-anvil ultra-high pressure die structure is proposed to solve the problem that the large-scale of the two-anvil ultra-high pressure die is limited by the difficulty in machining the large-size tungsten carbide. The die is mainly composed of an internal split cylinder with an inner cone and its support ring and the external steel wire winding layer. The stress distribution and cavity dimensional stability of the split cylinder are studied by using the finite element method and compared with those of the integral cylinder. This suggests that although the cavity-dimensional stability of the split ultra-high pressure die is reduced, the split ultra-high pressure die has greater advantages in improving the pressure-bearing capacity, processing, and manufacturing.

Comprehensive scientometrics and visualization study profiles lymphoma metabolism and identifies its significant research signatures.

Background: There is a wealth of poorly utilized unstructured data on lymphoma metabolism, and scientometrics and visualization study could serve as a robust tool to address this issue. Hence, it was implemented. Methods: After strict quality control, numerous data regarding the lymphoma metabolism were mined, quantified, cleaned, fused, and visualized from documents (n = 2925) limited from 2013 to 2022 using R packages, VOSviewer, and GraphPad Prism. Results: The linear fitting analysis generated functions predicting the annual publication number (y = 31.685x - 63628, R² = 0.93614, Prediction in 2027: 598) and citation number (y = 1363.7x - 2746019, R² = 0.94956, Prediction in 2027: 18201). In the last decade, the most academically performing author, journal, country, and affiliation were Meignan Michel (n = 35), European Journal of Nuclear Medicine and Molecular Imaging (n = 1653), USA (n = 3114), and University of Pennsylvania (n = 86), respectively. The hierarchical clustering based on unsupervised learning further divided research signatures into five clusters, including the basic study cluster (Cluster 1, Total Link Strength [TLS] = 1670, Total Occurrence [TO] = 832) and clinical study cluster (Cluster 3, TLS = 3496, TO = 1328). The timeline distribution indicated that radiomics and artificial intelligence (Cluster 4, Average Publication Year = 2019.39 ± 0.21) is a relatively new research cluster, and more endeavors deserve. Research signature burst and linear regression analysis further confirmed the findings above and revealed additional important results, such as tumor microenvironment (a = 0.6848, R² = 0.5194, p = 0.019) and immunotherapy (a = 1.036, R² = 0.6687, p = 0.004). More interestingly, by performing a "Walktrap" algorithm, the community map indicated that the "apoptosis, metabolism, chemotherapy" (Centrality = 12, Density = 6), "lymphoma, pet/ct, prognosis" (Centrality = 11, Density = 1), and "genotoxicity, mutagenicity" (Centrality = 9, Density = 4) are crucial but still under-explored, illustrating the potentiality of these research signatures in the field of the lymphoma metabolism. Conclusion: This study comprehensively mines valuable information and offers significant predictions about lymphoma metabolism for its clinical and experimental practice.

USP4 promotes the proliferation and glucose metabolism of gastric cancer cells by upregulating PKM2.

BACKGROUND: The pyruvate kinase enzyme PKM2 catalyzes the final step in glycolysis and converts phosphoenolpyruvate (PEP) to pyruvate. PKM2 is often overexpressed in cancer and plays a role in the Warburg effect. The expression of PKM2 can be regulated at different levels. While it has been proven that PKM2 can be regulated by ubiquitination, little is known about its de-ubiquitination regulation. METHODS: Immunoprecipitation was applied to identify the PKM2 interaction protein and to determine the interaction region between PKM2 and USP4. Immunofluorescence was performed to determine the cellular localization of USP4 and PKM2. The regulation of PKM2 by USP4 was examined by western blot and ubiquitination assay. MTT assays, glucose uptake, and lactate production were performed to analyze the biological effects of USP4 in gastric cancer cells. RESULTS: USP4 interacts with PKM2 and catalyzes the de-ubiquitination of PKM2. Overexpression of USP4 promotes cell proliferation, glucose uptake, and lactate production in gastric cancer cells. Knockdown of USP4 reduces PKM2 levels and results in a reduction in cell proliferation and the glycolysis rate. CONCLUSIONS: USP4 plays a tumor-promoting role in gastric cancer cells by regulating PKM2.

Second messenger signalling bypasses CGRP receptor blockade to provoke migraine attacks in humans.

There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine.

Single-cell RNA-seq analysis reveals that immune cells induce human nucleus pulposus ossification and degeneration.

Background and aims: Determining the transcriptomes and molecular mechanism underlying human degenerative nucleus pulposus (NP) is of critical importance for treating intervertebral disc degeneration (IDD). Here, we aimed to elucidate the detailed molecular mechanism of NP ossification and IDD using single-cell RNA sequencing. Methods: Single-cell RNA-seq and bioinformatic analysis were performed to identify NP cell populations with gene signatures, biological processes and pathways, and subpopulation analysis, RNA velocity analysis, and cell-to-cell communication analysis were performed in four IDD patients. We also verified the effects of immune cells on NP ossification using cultured NP cells and a well-established rat IDD model. Results: We identified five cell populations with gene expression profiles in degenerative NP at single-cell resolution. GO database analysis showed that degenerative NP-associated genes were mainly enriched in extracellular matrix organization, immune response, and ossification. Gene set enrichment analysis showed that rheumatoid arthritis signaling, antigen processing and presentation signaling were activated in the blood cell cluster. We revealed that stromal cells, which are progenitor cells, differentiated toward an ossification phenotype and delineated interactions between immune cells (macrophages and T cells) and stromal cells. Immune factors such as TNF-α, CD74 and CCL-3 promoted the differentiation of stromal cells toward an ossification phenotype in vitro. Blocking TNF-α with a specific inhibitor successfully reversed NP ossification and modified NP morphology in vivo. Conclusion: Our study revealed an increase in macrophages and T cells in degenerative NP, which induced stromal cell differentiation toward an ossification phenotype, and contributed to the identification of a novel therapeutic target to delay IDD.

Novel target and treatment agents for natural killer/T-cell lymphoma.

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

Metformin improves sheep sperm cryopreservation via vitalizing the AMPK pathway.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a key regulator of sperm function and physiological metabolism. Metformin, an inexpensive and effective antioxidant, is known to play an important role in the activation of AMPK. Therefore metformin has potential to improve sperm cryopreservation. The aim of this study was to investigate the effect of metformin during semen cryopreservation of sheep and to find the most effective concentration in freezing extender. Semen were cryopreserved with extender containing different concentrations of metformin (0, 0.25, 0.5, 1.0, 2.0 and 4.0 mmol/L). Sperm motility, acrosome integrity and plasma membrane integrity were measured after semen freezing and thawing. All results showed that sperm quality was significantly increased in the 1.0 mmol/L metformin-treated group compared with the control group (P < 0.05). In addition, the study showed that metformin effectively reduced the content of malondialdehyde (MDA) and reactive oxygen species (ROS), and increased the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) of freeze-thawed sperm (P < 0.05). The optimal concentration of metformin was 1.0 mmol/L. Moreover, the results showed that AMPK was localized in the acrosome region, junction and midsection of sperm, and p-AMPK was distributed in the post-acrosomal region, junction and midsection. Western blot analysis indicated that 1.0 mmol/L metformin stimulated the phosphorylation of AMPK in sperm. Further results showed that 1.0 mmol/L metformin significantly increased the mitochondrial membrane potential (ΔΨm), ATP content, glucose uptake and lactate efflux of post-thawed sperm through the AMPK pathway, improved sperm quality, and increased the cleavage rate of in vitro fertilization (P < 0.05).

A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response.

Background: Nrf2, an essential and fascinating transcription factor, enjoys a dual property in the occurrence and development of inflammation and cancer. For over two decades, numerous studies regarding Nrf2 in cancer have been reported, whereas there is still a lack of a scientometrics and visualization analysis of Nrf2 in cancer. Hence, a scientometric study regarding the oxidative stress modulator Nrf2 was implemented. Methods: After the quality screening, we defined 7168 relevant studies from 2000 to 2021. CiteSpace, VOSviewer, R software, and GraphPad Prism were used for the following scientometric study and visualization analysis, including field profiles, research hotspots, and future predictions. Results: The total number of publications and citations are 1058 and 54,690, respectively. After polynomial fitting curve analysis, two prediction functions of the annual publication number (y = 3.3909x2 - 13585x + 1 E+07) and citation number (185.45x2 - 743669x + 7 E+08) were generated. After scientometric analysis, we found that Biochemistry Molecular Biology correlates with Nrf2 in cancer highly, and Free Radical Biology and Medicine is a good choice for submitting Nrf2-related manuscripts. The current research hotspots of Nrf2 in cancer mainly focus on cancer therapy and its cellular and molecular mechanisms. "antioxidant response element (87.5)", "gene expression (43.98)", "antioxidant responsive element (21.14)", "chemoprevention (20.05)", "carcinogenesis (19.2)", "cancer chemoprevention (18.45)", "free radical (17.15)", "response element (14.17)", and "chemopreventive agent (14.04)" are important for cancer therapy study. In addition, "glutathione-S-transferase (47)", "keap1 (15.39)", and "heme oxygenase 1 gene (24.35)" are important for inflammation and cell fate study. More interestingly, by performing an "InfoMap" algorithm, the thematic map showed that the "immune response" is essential to oxidative stress modulator Nrf2 but not well developed, indicating it deserves further exploration. Conclusion: This study revealed field profiles, research hotspots, and future directions of oxidative stress modulator Nrf2 in inflammation and cancer research, and our findings will offer a vigorous roadmap for further studies in this field.

Water-soluble polymer brush-substituted squaraine NIR-II dye for efficient photothermal therapy.

Near-infrared II (NIR-II, 1000-1700 nm) fluorescence imaging has the advantages of low light scattering and weak biological autofluorescence compared with conventional NIR (600-900 nm) fluorescence imaging and can obtain a high signal-to-noise ratio in deeper biological tissues, as well as micron-level high resolution. A great deal of effort has been directed toward the construction of conjugated polymers for effective NIR-triggered fluorescence imaging (FI) and photothermal therapy (PTT) combined therapy. However, NIR-II fluorescent materials are mainly nanoparticles prepared by coprecipitation methods, and water-soluble NIR-II materials need to be further developed. In this paper, we synthesized novel water-soluble squaric acid nanoparticles (SQ-POEGMA) with low toxicity and excellent photostability by attaching a water-soluble oligomer (POEGMA) to the small molecule squaric acid through a click chemistry reaction. The photothermal conversion efficiency of SQ-POEGMA is 33% in vitro, which can effectively inhibit the growth of cancer cells with 94% tumor inhibition rate in vivo under 808 nm laser irradiation, while no appreciable side effects were observed.