Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

Characteristics of Subtype and Molecular Transmission Networks among Newly Diagnosed HIV-1 Infections in Patients Residing in Taiyuan City, Shanxi Province, China, from 2021 to 2023.

The HIV-1 pandemic, spanning four decades, presents a significant challenge to global public health. This study aimed to understand the molecular transmission characteristics of newly reported HIV infections in Taiyuan, Shanxi Province, China, to analyze the characteristics of subtypes and the risk factors of the transmission network, providing a scientific basis for precise prevention and intervention measures. A total of 720 samples were collected from newly diagnosed HIV-1 patients residing in Taiyuan between 2021 and 2023. Sequencing of partial genes of the HIV-1 pol gene resulted in multiple sequence acquisitions and was conducted to analyze their subtypes and molecular transmission networks. Out of the samples, 584 pol sequences were obtained, revealing 17 HIV-1 subtypes, with CRF07_BC (48.29%), CRF01_AE (31.34%), and CRF79_0107 (7.19%) being the dominant subtypes. Using a genetic distance threshold of 1.5%, 49 molecular transmission clusters were generated from the 313 pol gene sequences. Univariate analysis showed significant differences in the HIV transmission molecular network in terms of HIV subtype and household registration (p < 0.05). Multivariate logistic regression analysis showed that CRF79_0107 subtype and its migrants were associated with higher proportions of sequences in the HIV transmission network. These findings provide a scientific foundation for the development of localized HIV-specific intervention strategies.

Functional Characterization of Six Eukaryotic Translation Initiation Factors of Toxoplasma gondii Using the CRISPR-Cas9 System.

Eukaryotic translation initiation factors (eIFs) are crucial for initiating protein translation and ensuring the correct assembly of mRNA-ribosomal subunit complexes. In this study, we investigated the effects of deleting six eIFs in the apicomplexan parasite Toxoplasma gondii using the CRISPR-Cas9 system. We determined the subcellular localization of these eIFs using C-terminal endogenous tagging and immunofluorescence analysis. Four eIFs (RH::315150-6HA, RH::286090-6HA, RH::249370-6HA, and RH::211410-6HA) were localized in the cytoplasm, while RH::224235-6HA was localized in the apicoplast. Additionally, RH::272640-6HA was found in both the basal complex and the cytoplasm of T. gondii. Functional characterization of the six RHΔeIFs strains was conducted using plaque assay, cell invasion assay, intracellular growth assay and egress assay in vitro, and virulence assay in mice. Disruption of five eIF genes (RHΔ315150, RHΔ272640, RHΔ249370, RHΔ211410, and RHΔ224235) did not affect the ability of the T. gondii RH strain to invade, replicate, form plaques and egress in vitro, or virulence in Kunming mice (p > 0.05). However, the RHΔ286090 strain showed slightly reduced invasion efficiency and virulence (p < 0.01) compared to the other five RHΔeIFs strains and the wild-type strain. The disruption of the TGGT1_286090 gene significantly impaired the ability of tachyzoites to differentiate into bradyzoites in both type I RH and type II Pru strains. These findings reveal that the eukaryotic translation initiation factor TGGT1_286090 is crucial for T. gondii bradyzoite differentiation and may serve as a potential target for drug development and an attenuated vaccine against T. gondii.

GRA47 is important for the morphology and permeability of the parasitophorous vacuole in Toxoplasma gondii.

Establishing an intact intracellular parasitophorous vacuole (PV) that enables efficient nutrient uptake and protein trafficking is essential for the survival and proliferation of Toxoplasma gondii. Although the PV membrane (PVM)-localized dense granule protein 17 (GRA17) and GRA23 mediate the permeability of the PVM to small molecules, including nutrient uptake and excretion of metabolic by-products, the molecular mechanism by which T. gondii acquires nutrients remains unclear. In this study, we showed that the secreted protein GRA47 contributed to normal PV morphology, PVM permeability to small molecules, growth, and virulence in T. gondii. Co-immunoprecipitation analysis demonstrated potential interaction of GRA47 with GRA72, and the loss of GRA72 affected PV morphology, parasite growth and infectivity. To investigate the biological relationship among GRA47, GRA72, GRA17 and GRA23, attempts were made to construct strains with double gene deletion and overexpressing strains. Only Δgra23Δgra72 was successfully constructed. This strain exhibited a significant increase in the proportion of aberrant PVs compared with the Δgra23 strain. Overexpressing one of the three related GRAs partially rescued PVs with aberrant morphology in Δgra47, Δgra72 and Δgra17, while the expression of the Plasmodium falciparum PVM protein PfExp2, an ortholog of GRA17 and GRA23, fully rescued the PV morphological defect in all three Δgra strains. These results suggest that these GRA proteins may not be functionally redundant but rather work in different ways to regulate nutrient acquisition. These findings highlight the versatility of the nutrient uptake mechanisms in T. gondii, which may contribute to the parasite's remarkable ability to grow in different cellular niches in a very broad range of hosts.

PCAO2: an ontology for integration of prostate cancer associated genotypic, phenotypic and lifestyle data.

Disease ontologies facilitate the semantic organization and representation of domain-specific knowledge. In the case of prostate cancer (PCa), large volumes of research results and clinical data have been accumulated and needed to be standardized for sharing and translational researches. A formal representation of PCa-associated knowledge will be essential to the diverse data standardization, data sharing and the future knowledge graph extraction, deep phenotyping and explainable artificial intelligence developing. In this study, we constructed an updated PCa ontology (PCAO2) based on the ontology development life cycle. An online information retrieval system was designed to ensure the usability of the ontology. The PCAO2 with a subclass-based taxonomic hierarchy covers the major biomedical concepts for PCa-associated genotypic, phenotypic and lifestyle data. The current version of the PCAO2 contains 633 concepts organized under three biomedical viewpoints, namely, epidemiology, diagnosis and treatment. These concepts are enriched by the addition of definition, synonym, relationship and reference. For the precision diagnosis and treatment, the PCa-associated genes and lifestyles are integrated in the viewpoint of epidemiological aspects of PCa. PCAO2 provides a standardized and systematized semantic framework for studying large amounts of heterogeneous PCa data and knowledge, which can be further, edited and enriched by the scientific community. The PCAO2 is freely available at https://bioportal.bioontology.org/ontologies/PCAO, http://pcaontology.net/ and http://pcaontology.net/mobile/.

Proximity proteomics reveals UCH-L1 as an essential regulator of NLRP3-mediated IL-1ß production in human macrophages and microglia.

Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex is an essential innate immune signaling mechanism. To reveal how human NLRP3 inflammasome assembly and activation are controlled, in particular by components of the ubiquitin system, proximity labeling, affinity purification, and RNAi screening approaches were performed. Our study provides an intricate time-resolved molecular map of different phases of NLRP3 inflammasome activation. Also, we show that ubiquitin C-terminal hydrolase 1 (UCH-L1) interacts with the NACHT domain of NLRP3. Downregulation of UCH-L1 decreases pro-interleukin-1ß (IL-1ß) levels. UCH-L1 chemical inhibition with small molecules interfered with NLRP3 puncta formation and ASC oligomerization, leading to altered IL-1ß cleavage and secretion, particularly in microglia cells, which exhibited elevated UCH-L1 expression as compared to monocytes/macrophages. Altogether, we profiled NLRP3 inflammasome activation dynamics and highlight UCH-L1 as an important modulator of NLRP3-mediated IL-1ß production, suggesting that a pharmacological inhibitor of UCH-L1 may decrease inflammation-associated pathologies.

Immunization with Live-Attenuated RHΔhad2a Strain Confers Partial Protective Immunity against Acute and Chronic Infection of Toxoplasma gondii in Mice.

Toxoplasmosis caused by Toxoplasma gondii is an important zoonosis of human and animal health significance. Current chemical therapeutics have side effects, and no commercially available vaccine is licensed for the prevention of toxoplasmosis in humans and most animals. Developing a safe and effective vaccine with long-term protection against T. gondii infection is necessary to control toxoplasmosis. HAD2a is a key member of the haloacid dehalogenase (HAD) phosphatase family, which is essential for T. gondii daughter budding. However, the role of HAD2a in T. gondii virulence remains unknown. In this study, we successfully constructed the had2a gene knockout strain in the T. gondii-type I RH strain (RHΔhad2a) and determined its role in virulence and vaccination. These results demonstrate that HAD2a played an important role in parasite daughter budding and in vitro replication. Knockout of the had2a gene attenuated the virulence of the T. gondii-type I RH strain. Vaccination with RHΔhad2a tachyzoites induced a Th1-biased immune response, provided partial protection against acute T. gondii infection in mice by highly virulent tachyzoites of RH and PYS (ToxoDB#9, Chinese I) strains, and conferred strong protection against challenge infection by cysts and oocysts of the less virulent type II Pru strain. These results demonstrate that T. gondii had2a is important for its in vitro proliferation and virulence in mice and that RHΔhad2a may be used as a candidate strain to generate a multiple gene knockout live-attenuated strain or be collaboratively applied with other live-attenuated strains to confer more effective protection against T. gondii infection.

Preoperative low plasma creatine kinase levels predict worse survival outcomes in bladder cancer after radical cystectomy.

BACKGROUND AND AIMS: To evaluate the prognostic significance of preoperative creatine kinase (CK) levels in bladder cancer (BCa) patients who underwent radical cystectomy (RC). MATERIALS AND METHODS: 570 BCa patients with RC were identified between 2010 and 2020. 108.5 U/L of CK levels were defined as the cutoff value. Logistic regression analysis and Cox regression models were performed to evaluate the association between CK levels and oncologic outcomes. Subgroup analyses were performed to address cofounding factors. RESULTS: Preoperative low CK levels were associated with worse recurrence-free survival (RFS, log-rank P = 0.001) and overall survival (OS, log-rank P = 0.002). Multivariate analysis revealed that preoperative low CK levels were an independent predictor for worse RFS (hazard ratio [HR]: 1.683; P < 0.001) and OS (HR: 1.567; P = 0.002). CONCLUSIONS: The preoperative low CK level independently predicts worse survival outcomes in BCa after RC. Incorporating it into prediction models might be valuable to assist risk stratification.