Investigating the characteristics of mild intervertebral disc degeneration at various age stages using single-cell genomics.

Introduction: Intervertebral disc degeneration often occurs in the elderly population, but in recent years, there has been an increasing incidence of disc degeneration in younger individuals, primarily with mild degeneration. Methods: In order to explore the underlying mechanisms of disc degeneration in both young and aging individuals, we collected four types of nucleus pulposus (NP) single-cell sequencing samples for analysis based on Pfirrmann grading: normal-young (NY) (Grade I), normal-old (NO) (Grade I), mild degenerative-young (MY) (Grade II-III), and mild degenerative-old (MO) (Grade II-III). Results: We found that most NP cells in NO and MY samples exhibited oxidative stress, which may be important pathogenic factors in NO and MY groups. On the other hand, NP cells in MO group exhibited endoplasmic reticulum stress. In terms of inflammation, myeloid cells were mainly present in the degenerative group, with the MY group showing a stronger immune response compared to the MO group. Interestingly, dendritic cells in the myeloid lineage played a critical role in the process of mild degeneration. Discussion: Our study investigated the molecular mechanisms of intervertebral disc degeneration from an age perspective, providing insights for improving treatment strategies for patients with disc degeneration at different age groups.

Pterostilbene alleviates MPTP-induced neurotoxicity by targeting neuroinflammation and oxidative stress.

Pterostilbene (PTE), a naturally occurring phenolic compound primarily found in blueberries, demonstrates neuroprotective properties. However, the role of PTE in Parkinson's disease (PD) remains unclear. This study aimed to investigate the neuroprotective role of PTE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our findings demonstrate that administering PTE effectively reversed the diminished levels of dopamine in the striatum, thereby ameliorating motor impairments in the MPTP model. Moreover, PTE administration mitigated the loss of dopaminergic (DA) neurons and reduced the upregulation of α-synuclein (α-syn) induced by MPTP. Mechanistic analysis revealed that PTE administration inhibited the activation of microglia and astrocytes, as well as pro-inflammatory factors such as TNF-α and IL-1ß in the MPTP model. Additionally, PTE administration decreased MPTP-induced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing total antioxidant capacity (TAOC) and superoxide dismutase (SOD) activity, thereby attenuating oxidative stress. Collectively, these findings demonstrate that PTE exerts neuroprotective effects in the MPTP mouse model of PD by suppressing neuroinflammation and oxidative stress. Thus, PTE holds promise as a therapeutic agent for PD.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking.

BACKGROUND: Hypertrophic scar (HTS) is dermal fibroproliferative disorder, which may cause physiological and psychological problems. Currently, the potential mechanism of WuFuYin (WFY) in the treatment of HTS remained to be elucidated. AIM: To explore the potential mechanism of WFY in treating HTS. METHODS: Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HTS-related genes were obtained from the GeneCards, DisGeNET, and National Center for Biotechnology Information. The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analysis. A protein + IBM-protein interaction (PPI) network was developed using STRING database and Cytoscape. To confirm the high affinity between compounds and targets, molecular docking was performed. RESULTS: A total of 65 core genes, which were both related to compounds and HTS, were selected from multiple databases. PPI analysis showed that CKD2, ABCC1, MMP2, MMP9, glycogen synthase kinase 3 beta (GSK3B), PRARG, MMP3, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the hub targets and MOL004941, MOL004935, MOL004866, MOL004993, and MOL004989 were the key compounds of WFY against HTS. The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway. Moreover, by performing molecular docking, we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity. CONCLUSION: The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941, MOL004989, and MOL004993 were the main compounds of WFY in HTS treatment.

Data Quality-Aware Mixed-Precision Quantization via Hybrid Reinforcement Learning.

Mixed-precision quantization mostly predetermines the model bit-width settings before actual training due to the non-differential bit-width sampling process, obtaining suboptimal performance. Worse still, the conventional static quality-consistent training setting, i.e., all data is assumed to be of the same quality across training and inference, overlooks data quality changes in real-world applications which may lead to poor robustness of the quantized models. In this article, we propose a novel data quality-aware mixed-precision quantization framework, dubbed DQMQ, to dynamically adapt quantization bit-widths to different data qualities. The adaption is based on a bit-width decision policy that can be learned jointly with the quantization training. Concretely, DQMQ is modeled as a hybrid reinforcement learning (RL) task that combines model-based policy optimization with supervised quantization training. By relaxing the discrete bit-width sampling to a continuous probability distribution that is encoded with few learnable parameters, DQMQ is differentiable and can be directly optimized end-to-end with a hybrid optimization target considering both task performance and quantization benefits. Trained on mixed-quality image datasets, DQMQ can implicitly select the most proper bit-width for each layer when facing uneven input qualities. Extensive experiments on various benchmark datasets and networks demonstrate the superiority of DQMQ against existing fixed/mixed-precision quantization methods.

Scorpion venom heat-resistant synthesized peptide ameliorates epileptic seizures and imparts neuroprotection in rats mediated by NMDA receptors.

Finding new and effective natural products for designing antiepileptic drugs is highly important in the scientific community. The scorpion venom heat-resistant peptide (SVHRP) was purified from Buthus martensii Karsch scorpion venom, and subsequent analysis of the amino acid sequence facilitated the synthesis of a peptide known as scorpion venom heat-resistant synthesis peptide (SVHRSP) using a technique for peptide synthesis. Previous studies have demonstrated that the SVHRSP can inhibit neuroinflammation and provide neuroprotection. This study aimed to investigate the antiepileptic effect of SVHRSP on both acute and chronic kindling seizure models by inducing seizures in male rats through intraperitoneal administration of pentylenetetrazole (PTZ). Additionally, an N-methyl-D-aspartate (NMDA)-induced neuronal injury model was used to observe the anti-excitotoxic effect of SVHRSP in vitro. Our findings showed that treatment with SVHRSP effectively alleviated seizure severity, prolonged latency, and attenuated neuronal loss and glial cell activation. It also demonstrated the prevention of alterations in the expression levels of NMDA receptor subunits and phosphorylated p38 MAPK protein, as well as an improvement in spatial reference memory impairment during Morris water maze (MWM) testing in PTZ-kindled rats. In vitro experiments further revealed that SVHRSP was capable of attenuating neuronal action potential firing, inhibiting NMDA receptor currents and intracellular calcium overload, and reducing neuronal injury. These results suggest that the antiepileptic and neuroprotective effects of SVHRSP may be mediated through the regulation of NMDA receptor function and expression. This study provides new insight into therapeutic strategies for epilepsy.

Molecular nociceptive mechanisms in migraine: The migraine cascade.

OBJECTIVE: This review will explore the categorization of migraine-provoking molecules, their cellular actions, site of action and potential drug targets based on the migraine cascade model. METHODS: Personal experience and literature. RESULTS: Migraine impacts over 1 billion people worldwide but is underfunded in research. Recent progress, particularly through the human and animal provocation model, has deepened our understanding of its mechanisms. This model have identified endogenous neuropeptides such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) that induces controlled migraine-like attacks leading to significant discoveries of their role in migraine. This knowledge led to the development of CGRP-inhibiting drugs; a groundbreaking migraine treatment now accessible globally. Also a PACAP-inhibiting drug was effective in a recent phase II trial. Notably, rodent studies have shed light on pain pathways and the mechanisms of various migraine-inducing substances identifying novel drug targets. This is primarily done by using selective inhibitors that target specific signaling pathways of the known migraine triggers leading to the hypothesized cellular cascade model of migraine. CONCLUSION: The model of migraine presents numerous opportunities for innovative drug development. The future of new migraine treatments is limited only by the investment from pharmaceutical companies.

Complete androgen insensitivity syndrome coexisting with müllerian duct remnants: a case report and literature review.

This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland China. Additionally, we provide a comprehensive review of the existing literature concerning CAIS with MDRs resulting from androgen receptor (AR) gene mutations. This study broadens the clinical spectrum of CAIS and offer novel insights for further exploration into Müllerian duct regression. A 14-year-old patient, initially raised as female, presented to the clinic with complaints of "primary amenorrhea." Physical examination revealed the following: armpit hair (Tanner stage 2), breast development (Tanner stage 4 with bilateral breast nodule diameter of 7 cm), sparse pubic hair (Tanner stage 3), clitoris measuring 0.8 cm × 0.4 cm, separate urethral and vaginal openings, and absence of palpable masses in the bilateral groin or labia majora. The external genital virilization score was 0 points. Serum follicle-stimulating hormone level was 13.43 IU/L, serum luteinizing hormone level was 31.24 IU/L, and serum testosterone level was 14.95 nmol/L. Pelvic magnetic resonance imaging (MRI) did not reveal a uterus or bilateral fallopian tubes, but nodules on both sides of the pelvic wall indicated cryptorchidism. The karyotype was 46,XY. Genetic testing identified a maternal-derived hemizygous variation c.2359C > T (p.Arg787*) in the AR gene. During abdominal exploration, dysplastic testicles and a dysplastic uterus were discovered. Histopathological analysis revealed the presence of fallopian tube-like structures adjacent to the testicles. The CAIS patient documented in this study exhibited concurrent MDRs, thus expanding the spectrum of clinical manifestations of AIS. A review of prior literature suggests that the incidence of CAIS combined with histologically MDRs is not uncommon. Consequently, the identification of MDRs in AIS cases may represent an integral aspect of clinical diagnosis for this condition.

Study on the susceptibility of bovine coronavirus to BALB/c mice.

There are no other bovine coronavirus (BCoV) infection models except calves, which makes efficacy evaluation of vaccines and pathogenic mechanism research of BCoV inconvenient owing to their high value and inconvenient operation. This study aimed to establish a mouse model of BCoV infection. BCoV was used to infect 4-week-old male BALB/c mice and the optimal infection conditions were screened, including the following infection routes: gavage, intraperitoneal injection, and tail vein injection at doses of 1 × 108 TCID50, 2 × 108 TCID50 and 4 × 108 TCID50. Using the optimal infection conditions, BALB/c mice were infected with BCoV, and their body weight, blood routine, inflammatory factors, autopsy, virus distribution, and viral load were measured at 1, 3, 5, and 7 days after infection. The results showed that the optimal conditions for infecting BALB/c mice with BCoV HLJ-325 strain were continuous oral gavage for 3 days with a dose of 4 × 108 TCID50. On the 7th day after infection, there was significant extensive consolidation of the lungs and thinning of the colon wall. Significant inflammation was observed in various organs, especially in the colon and alveoli, where a large number of inflammatory cells infiltrate. Both BCoV Ag and nucleic acid are positive in visceral organs. The viral load in the colon and lungs was significantly higher than that in the other organs (p < 0.001). BCoV-infected mice showed a decreasing trend in body weight starting from day 5, and there was a significant difference compared to the control group on days 6 and 7 (p < 0.001). The total number of white blood cells and lymphocytes began to decrease and was significantly lower than that in the control group 24 h after infection (p < 0.001), and gradually returned to the control level. The cytokine TNF-α, IL-1ß, and IL-6 showed an increasing trend, significantly higher than the control group on day 5 and 7 (p < 0.001). These results indicate that the BCoV HLJ-325 strain can infect BALB/c mice and cause inflammatory reactions and tissue lesions. The most significant effect was observed on the seventh day after infection with a dose of 4 × 108 TCID50 and three consecutive gavages. This study established, for the first time, a BALB/c mouse model of BCoV infection, providing a technical means for evaluating the immune efficacy of BCoV vaccines and studying their pathogenic mechanisms.

Modeling the molecular composition of secondary organic aerosol under highly polluted conditions: A case study in the Yangtze River Delta Region in China.

A near-explicit mechanism, the master chemical mechanism (MCMv3.3.1), coupled with the Community Multiscale Air Quality (CMAQ) model (CMAQ-MCM-SOA), was applied to investigate the characteristics of secondary organic aerosol (SOA) during a pollution event in the Yangtze River Delta (YRD) region in summer 2018. Model performances in predicting explicit volatile organic compounds (VOCs), organic aerosol (OA), secondary organic carbon (SOC), and other related pollutants in Taizhou, as well as ozone (O3) and fine particulate matter (PM2.5) in multiple cities in this region, were evaluated against observations and model predictions by the CMAQ model coupled with a lumped photochemical mechanism (SAPRC07tic, S07). MCM and S07 exhibited similar performances in predicting gaseous species, while MCM better captured the observed PM2.5 and inorganic aerosols. Both models underpredicted OA concentrations. When excluding data during biomass burning events, SOC concentrations were underpredicted by the CMAQ-MCM-SOA model (-28.4 %) and overpredicted by the CMAQ-S07 model (134.4 %), with better agreement with observations in the trend captured by the CMAQ-MCM-SOA model. Dicarbonyl SOA accounted for a significant fraction of total SOA in the YRD, while organic nitrates originating from aromatics were the most abundant species contributing to the SOA formation from gas-particle partitioning. The oxygen-to­carbon ratio (O/C) for SOA and OA were 0.68-0.75 and 0.20-0.65, respectively, indicating a higher oxidation state in the areas influenced by biogenic emissions. Finally, the phase state of SOA was examined by calculating the glass transition temperature (Tg) based on its molecular composition. It was found that semi-solid state characterized SOA in the YRD, which could potentially impact their chemical transformation and lifetimes along with those of their precursors.

Amorphous MnRuOx Containing Microcrystalline for Enhanced Acidic Oxygen-Evolution Activity and Stability.

Compared to Ir, Ru-based catalysts often exhibited higher activity but suffered significant and rapid activity loss during the challenging oxygen evolution reaction (OER) in a corrosive acidic environment. Herein, we developed a hybrid MnRuOx catalyst in which the RuO2 microcrystalline regions serve as a supporting framework, and the amorphous MnRuOx phase fills the microcrystalline interstices. In particular, the MnRuOx-300 catalyst from an annealing temperature of 300 °C contains an optimal amorphous/crystalline heterostructure, providing substantial defects and active sites, facilitating efficient adsorption and conversion of OH-. In addition, the heterostructure leads to a relative increase of the d-band center close to the Fermin level, thus accelerating electron transfer with reduced charge transfer resistance at the active interface between crystalline and amorphous phases during the OER. The catalyst was further thoroughly evaluated under various operating conditions and demonstrated exceptional activity and stability for the OER, representing a promising solution to replace Ir in water electrolyzers.

Earth-abundant Zn-dipyrrin chromophores for efficient CO2 photoreduction.

The development of strong sensitizing and Earth-abundant antenna molecules is highly desirable for CO2 reduction through artificial photosynthesis. Herein, a library of Zn-dipyrrin complexes (Z-1-Z-6) are rationally designed via precisely controlling their molecular configuration to optimize strong sensitizing Earth-abundant photosensitizers. Upon visible-light excitation, their special geometry enables intramolecular charge transfer to induce a charge-transfer state, which was first demonstrated to accept electrons from electron donors. The resulting long-lived reduced photosensitizer was confirmed to trigger consecutive intermolecular electron transfers for boosting CO2-to-CO conversion. Remarkably, the Earth-abundant catalytic system with Z-6 and Fe-catalyst exhibits outstanding performance with a turnover number of >20 000 and 29.7% quantum yield, representing excellent catalytic performance among the molecular catalytic systems and highly superior to that of noble-metal photosensitizer Ir(ppy)2(bpy)+ under similar conditions. Experimental and theoretical investigations comprehensively unveil the structure-activity relationship, opening up a new horizon for the development of Earth-abundant strong sensitizing chromophores for boosting artificial photosynthesis.

Widespread 2013-2020 decreases and reduction challenges of organic aerosol in China.

High concentrations of organic aerosol (OA) occur in Asian countries, leading to great health burdens. Clean air actions have resulted in significant emission reductions of air pollutants in China. However, long-term nation-wide trends in OA and their causes remain unknown. Here, we present both observational and model evidence demonstrating widespread decreases with a greater reduction in primary OA than in secondary OA (SOA) in China during the period of 2013 to 2020. Most of the decline is attributed to reduced residential fuel burning while the interannual variability in SOA may have been driven by meteorological variations. We find contrasting effects of reducing NOx and SO2 on SOA production which may have led to slight overall increases in SOA. Our findings highlight the importance of clean energy replacements in multiple sectors on achieving air-quality targets because of high OA precursor emissions and fluctuating chemical and meteorological conditions.

Lipidome atlas of the adult human brain.

Lipids are the most abundant but poorly explored components of the human brain. Here, we present a lipidome map of the human brain comprising 75 regions, including 52 neocortical ones. The lipidome composition varies greatly among the brain regions, affecting 93% of the 419 analyzed lipids. These differences reflect the brain's structural characteristics, such as myelin content (345 lipids) and cell type composition (353 lipids), but also functional traits: functional connectivity (76 lipids) and information processing hierarchy (60 lipids). Combining lipid composition and mRNA expression data further enhances functional connectivity association. Biochemically, lipids linked with structural and functional brain features display distinct lipid class distribution, unsaturation extent, and prevalence of omega-3 and omega-6 fatty acid residues. We verified our conclusions by parallel analysis of three adult macaque brains, targeted analysis of 216 lipids, mass spectrometry imaging, and lipidome assessment of sorted murine neurons.

Understanding secondary particles in a regional site of Yangtze River Delta: Insights from mass spectrometric measurement.

Submicron particulate matter (PM1) poses significant risks to health risks and global climate. In this study, secondary organic aerosols (SOA) and inorganic compositions were examined for their physicochemical characteristics and evolution using high-resolution aerosol instruments in Changzhou over one-month period. The results showed that transport accompanied by regional static conditions leaded to the occurrence of heavy pollution. In addition, regional generation and local emissions also leaded to the occurrence of light and moderate pollution during the observation period in Changzhou. Organic aerosols (OA) and nitrate (NO3-) accounted for 45 % and 23 % of PM1, respectively. The increase in PM1 was dominated by the contribution of NO3- and OA. SOA was dominance in OA (63 % with 40 % MO-OOA), which was higher than primary organic aerosols (POA). Besides, photochemical reactions and the high oxidizing nature of the urban atmosphere promoted the production of OA, especially MO-OOA in Changzhou. Our results highlight that secondary particles contribute significantly to PM pollution in Changzhou, underlining the importance of controlling emissions of gaseous precursors, especially under high oxidation conditions.

Enhancing the Performance of 2D Ni-Fe Layered Double Hydroxides by Cabbage-Inspired Carbon Conjunction for Oxygen Evolution Reactions.

Layered double hydroxide (LDH) nanosheets as one type of two-dimensional materials have garnered increasing attention in the field of oxygen evolution reaction (OER) in recent decades. To address the challenges associated with poor conductivity and limited electron and charge transfer capability in LDH materials, we have developed a straightforward one-pot synthesis method to successfully fabricate a composite material with a microstructure resembling cabbage, which encompasses NiFe-LDH and nanocarbon (referred as NiFe-LDH@C). Atomic force microscopy (AFM) and high-resolution transmission electron microscopy (HRTEM) revealed that the monolayer NiFe-LDH with a height of ~0.5-0.8 nm is uniformly distributed and closely bonded to the carbon support, leading to a significant enhancement in conductivity and facilitating faster electron and charge transfer. Moreover, the NiFe-LDH@C exhibits a substantial number of surface defect sites, which enhances the interaction with oxygen species. This dual enhancement in charge transfer and oxygen species-mediated transfer greatly improves the catalytic OER performance, which is further corroborated by theoretical calculations. Notably, the Ni10Fe6-LDH@C with the highest concentration of surface oxygen vacancies demonstrated superior water oxidation performance, surpassing commercially available RuO2 catalysts; an OER overpotential of 231 mV@10 mA cm-2 with a Tafel slope of 71 mV dec-1 was achieved.

Building Co16-N3-Based UiO-MOF to Expand Design Parameters for MOF Photosensitization.

The construction of secondary building units (SBUs) in versatile metal-organic frameworks (MOFs) represents a promising method for developing multi-functional materials, especially for improving their sensitizing ability. Herein, we developed a dual small molecules auxiliary strategy to construct a high-nuclear transition-metal-based UiO-architecture Co16-MOF-BDC with visible-light-absorbing capacity. Remarkably, the N3 - molecule in hexadecameric cobalt azide SBU offers novel modification sites to precise bonding of strong visible-light-absorbing chromophores via click reaction. The resulting Bodipy@Co16-MOF-BDC exhibits extremely high performance for oxidative coupling benzylamine (~100 % yield) via both energy and electron transfer processes, which is much superior to that of Co16-MOF-BDC (31.5 %) and Carboxyl @Co16-MOF-BDC (37.5 %). Systematic investigations reveal that the advantages of Bodipy@Co16-MOF-BDC in dual light-absorbing channels, robust bonding between Bodipy/Co16 clusters and efficient electron-hole separation can greatly boost photosynthesis. This work provides an ideal molecular platform for synergy between photosensitizing MOFs and chromophores by constructing high-nuclear transition-metal-based SBUs with surface-modifiable small molecules.

Pharmacology of PACAP and VIP receptors in the spinal cord highlights the importance of the PAC1 receptor.

BACKGROUND AND PURPOSE: The spinal cord is a key structure involved in the transmission and modulation of pain. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP), are expressed in the spinal cord. These peptides activate G protein-coupled receptors (PAC1, VPAC1 and VPAC2) that could provide targets for the development of novel pain treatments. However, it is not clear which of these receptors are expressed within the spinal cord and how these receptors signal. EXPERIMENTAL APPROACH: Dissociated rat spinal cord cultures were used to examine agonist and antagonist receptor pharmacology. Signalling profiles were determined for five signalling pathways. The expression of different PACAP and VIP receptors was then investigated in mouse, rat and human spinal cords using immunoblotting and immunofluorescence. KEY RESULTS: PACAP, but not VIP, potently stimulated cAMP, IP1 accumulation and ERK and cAMP response element-binding protein (CREB) but not Akt phosphorylation in spinal cord cultures. Signalling was antagonised by M65 and PACAP6-38. PACAP-27 was more effectively antagonised than either PACAP-38 or VIP. The patterns of PAC1 and VPAC2 receptor-like immunoreactivity appeared to be distinct in the spinal cord. CONCLUSIONS AND IMPLICATIONS: The pharmacological profile in the spinal cord suggested that a PAC1 receptor is the major functional receptor subtype present and thus likely mediates the nociceptive effects of the PACAP family of peptides in the spinal cord. However, the potential expression of both PAC1 and VPAC2 receptors in the spinal cord highlights that these receptors may play differential roles and are both possible therapeutic targets.

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.

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.