CT-based radiomics nomogram to predict proliferative hepatocellular carcinoma and explore the tumor microenvironment.

BACKGROUND: Proliferative hepatocellular carcinomas (HCCs) is a class of aggressive tumors with poor prognosis. We aimed to construct a computed tomography (CT)-based radiomics nomogram to predict proliferative HCC, stratify clinical outcomes and explore the tumor microenvironment. METHODS: Patients with pathologically diagnosed HCC following a hepatectomy were retrospectively collected from two medical centers. A CT-based radiomics nomogram incorporating radiomics model and clinicoradiological features to predict proliferative HCC was constructed using the training cohort (n = 184), and validated using an internal test cohort (n = 80) and an external test cohort (n = 89). The predictive performance of the nomogram for clinical outcomes was evaluated for HCC patients who underwent surgery (n = 201) or received transarterial chemoembolization (TACE, n = 104). RNA sequencing data and histological tissue slides from The Cancer Imaging Archive database were used to perform transcriptomics and pathomics analysis. RESULTS: The areas under the receiver operating characteristic curve of the radiomics nomogram to predict proliferative HCC were 0.84, 0.87, and 0.85 in the training, internal test, and external test cohorts, respectively. The radiomics nomogram could stratify early recurrence-free survivals in the surgery outcome cohort (hazard ratio [HR] = 2.25; P < 0.001) and progression-free survivals in the TACE outcome cohort (HR = 2.21; P = 0.03). Transcriptomics and pathomics analysis indicated that the radiomics nomogram was associated with carbon metabolism, immune cells infiltration, TP53 mutation, and heterogeneity of tumor cells. CONCLUSION: The CT-based radiomics nomogram could predict proliferative HCC, stratify clinical outcomes, and measure a pro-tumor microenvironment.

Ignored microbial-induced taste and odor in drinking water reservoirs: Novel insight into actinobacterial community structure, assembly, and odor-producing potential.

The presence of actinobacteria in reservoirs can lead to taste and odor issues, posing potential risks to the safety of drinking water supply. However, the response of actinobacterial communities to environmental factors in drinking water reservoirs remains largely unexplored. To address this gap, this study investigated the community structure and metabolic characteristics of odor-producing actinobacteria in water reservoirs across northern and southern China. The findings revealed differences in the actinobacterial composition across the reservoirs, with Mycobacterium sp. and Candidatus Nanopelagicus being the most prevalent genera. Notably, water temperature, nutrient levels, and metal concentrations were associated with differences in actinobacterial communities, with stochastic processes playing a major role in shaping the community assembly. In addition, three strains of odor-producing actinobacteria were cultured in raw reservoir water, namely Streptomyces antibioticus LJH21, Streptomyces sp. ZEU13, and Streptomyces sp. PQK19, with peak ATP concentrations of 51 nmol/L, 66 nmol/L, and 70 nmol/L, respectively, indicating that odor-producing actinobacteria could remain metabolically active under poor nutrient pressure. Additionally, Streptomyces antibioticus LJH21 produced the highest concentration of geosmin at 24.4 ng/L. These findings enhance our understanding of regional variances and reproductive metabolic mechanisms of actinobacteria in drinking water reservoirs, providing a solid foundation for improving drinking water quality control, especially for taste and odor.

Mixotrophic aerobic denitrification facilitated by denitrifying bacterial-fungal communities assisted with iron in micro-polluted water: Performance, metabolic activity, functional genes abundance, and community co-occurrence.

Low-dosage nitrate pollutants can contribute to eutrophication in surface water bodies, such as lakes and reservoirs. This study employed assembled denitrifying bacterial-fungal communities as bio-denitrifiers, in combination with zero-valent iron (ZVI), to treat micro-polluted water. Immobilized bacterial-fungal mixed communities (IBFMC) reactors demonstrated their ability to reduce nitrate and organic carbon by over 43.2 % and 53.7 %, respectively. Compared to IBFMC reactors, IBFMC combined with ZVI (IBFMC@ZVI) reactors exhibited enhanced removal efficiencies for nitrate and organic carbon, reaching the highest of 31.55 % and 17.66 %, respectively. The presence of ZVI in the IBFMC@ZVI reactors stimulated various aspects of microbial activity, including the metabolic processes, electron transfer system activities, abundance of functional genes and enzymes, and diversity and richness of microbial communities. The contents of adenosine triphosphate and electron transfer system activities enhanced more than 5.6 and 1.43 folds in the IBFMC@ZVI reactors compared with IBFMC reactors. Furthermore, significant improvement of crucial genes and enzyme denitrification chains was observed in the IBFMC@ZVI reactors. Iron played a central role in enhancing microbial diversity and activity, and promoting the supply, and transfer of inorganic electron donors. This study presents an innovative approach for applying denitrifying bacterial-fungal communities combined with iron enhancing efficient denitrification in micro-polluted water.

Crosstalking with Dendritic Cells: A Path to Engineer Advanced T Cell Immunotherapy.

Crosstalk between dendritic cells (DCs) and T cells plays a crucial role in modulating immune responses in natural and pathological conditions. DC-T cell crosstalk is achieved through contact-dependent (i.e., immunological synapse) and contact-independent mechanisms (i.e., cytokines). Activated DCs upregulate co-stimulatory signals and secrete proinflammatory cytokines to orchestrate T cell activation and differentiation. Conversely, activated T helper cells "license" DCs towards maturation, while regulatory T cells (Tregs) silence DCs to elicit tolerogenic immunity. Strategies to efficiently modulate the DC-T cell crosstalk can be harnessed to promote immune activation for cancer immunotherapy or immune tolerance for the treatment of autoimmune diseases. Here, we review the natural crosstalk mechanisms between DC and T cells. We highlight bioengineering approaches to modulate DC-T cell crosstalk, including conventional vaccines, synthetic vaccines, and DC-mimics, and key seminal studies leveraging these approaches to steer immune response for the treatment of cancer and autoimmune diseases.

Algicidal activity synchronized with nitrogen removal by actinomycetes: Algicidal mechanism, stress response of algal cells, denitrification performance, and indigenous bacterial community co-occurrence.

The harmful algal blooms (HABs) can damage the ecological equilibrium of aquatic ecosystems and threaten human health. The bio-degradation of algal by algicidal bacteria is an environmentally friendly and economical approach to control HABs. This study applied an aerobic denitrification synchronization algicidal strain Streptomyces sp. LJH-12-1 (L1) to control HABs. The cell-free filtrate of the strain L1 showed a great algolytic effect on bloom-forming cyanobacterium, Microcystis aeruginosa (M. aeruginosa). The optimal algicidal property of strain L1 was indirect light-dependent algicidal with an algicidal rate of 85.0%. The functional metabolism, light-trapping, light-transfer efficiency, the content of pigments, and inhibition of photosynthesis of M. aeruginosa decreased after the addition of the supernatant of the strain L1 due to oxidative stress. Moreover, 96.05% nitrate removal rate synchronized with algicidal activity was achieved with the strain L1. The relative abundance of N cycling functional genes significantly increased during the strain L1 effect on M. aeruginosa. The algicidal efficiency of the strain L1 in the raw water was 76.70% with nitrate removal efficiency of 81.4%. Overall, this study provides a novel route to apply bacterial strain with the property of denitrification coupled with algicidal activity in treating micro-polluted water bodies.

Aged-Signal-Eliciting Nanoparticles Stimulated Macrophage-Mediated Programmed Removal of Inflammatory Neutrophils.

Excessive infiltration of activated neutrophils is regarded as a predominant cause of tissue injury in neutrophilic inflammation. Although programmed cell death like apoptosis maintains the homeostasis of activated neutrophils, this process is disrupted by an abnormal inflammatory response. Unlike endogenous calreticulin exposed during apoptosis, exogenous calreticulin acts as an "aged" signal and initiates premature macrophage-mediated programmed cell removal (PrCR), which is independent of apoptosis. Here, we report a nano-mediated strategy to stimulate the precise clearance of activated neutrophils initiated with artificial aged signal and alleviated inflammation. Polymeric nanoparticles PC@PLGA were fabricated by cloaking poly(lactic-co-glycolic acid) (PLGA) with a hybrid membrane derived from platelet-derived extracellular vesicles (PEVs, denoted by P) and the calreticulin-expressed membrane obtained from doxorubicin-treated cells (denoted by C). P-selectin in PEVs favors PC@PLGA to anchor activated neutrophils, while calreticulin mimics exogenous "aged" signal secreted by macrophages to trigger PrCR. We showed that PC@PLGA specifically targeted activated neutrophils and misled macrophages to recognize them as "aged" neutrophils and then initiated premature PrCR and prevented proinflammatory response and tissue damage in a mouse model of acute lung injury and severe acute pancreatitis. The collective findings indicate the efficiency of specific elimination of activated neutrophils with exogenous aged signal in improving inflammation therapy.

Prediction model based on radiomics and clinical features for preoperative lymphovascular invasion in gastric cancer patients.

Background: We explored whether a model based on contrast-enhanced computed tomography radiomics features and clinicopathological factors can evaluate preoperative lymphovascular invasion (LVI) in patients with gastric cancer (GC) with Lauren classification. Methods: Based on clinical and radiomic characteristics, we established three models: Clinical + Arterial phase_Radcore, Clinical + Venous phase_Radcore and a combined model. The relationship between Lauren classification and LVI was analyzed using a histogram. Results: We retrospectively analyzed 495 patients with GC. The areas under the curve of the combined model were 0.8629 and 0.8343 in the training and testing datasets, respectively. The combined model showed a superior performance to the other models. Conclusion: CECT-based radiomics models can effectively predict preoperative LVI in GC patients with Lauren classification.

In Situ Albumin-Hitchhiking NIR-II Probes for Accurate Detection of Micrometastases.

Tumor metastasis remains the primary cause of treatment failure in cancer patients, and the high-sensitivity preoperative and intraoperative detection of occult micrometastases continues to pose a notorious challenge. Therefore, we have designed an in situ albumin-hitchhiking near-infrared window II (NIR-II) fluorescence probe, IR1080, for the precise detection of micrometastases and subsequent fluorescence image-guided surgery. IR1080 rapidly covalently conjugates with albumin in plasma, resulting in a stronger fluorescence brightness upon binding. Moreover, the albumin-hitchhiked IR1080 has a high affinity for secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein that is overexpressed in micrometastases. The interaction between SPARC and IR1080-hitchhiked albumin enhances IR1080's capacity to track and anchor micrometastases, leading to a high detection rate and margin delineation ability, as well as a high tumor-to-normal tissue ratio. Therefore, IR1080 represents a highly efficient strategy for the diagnosis and image-guided resection surgery of micrometastases.

Effects of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer: a retrospective study grouped based on the relationship between the bottom of the tumor and peritoneal reflection.

Background: To evaluate the effect of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer based on the relationship between the bottom of the tumor and peritoneal reflection. Methods: A retrospective study was performed on 694 patients who underwent radical resection for rectal cancer at the Harbin Medical University Tumor Hospital from October 2016 to October 2021. According to the surgical records, a new group was established based on the relationship between the lower end of the tumor and peritoneal reflection. On the peritoneal reflection group: the tumors are all located on the peritoneal reflection. Across the peritoneal reflection group: the tumors recurred across the peritoneal reflection. Under the peritoneal reflection group: the tumors are all located under the peritoneal reflection. We evaluated the effects of mrEMVI and TDs on postoperative distant metastasis and long-term survival of stage III rectal cancer by combining mrEMVI with TDs. Results: In the whole study population, neoadjuvant therapy (P=0.003) was negatively correlated with distant metastasis after rectal cancer surgery. Also, mesorectal fascia (MRF) (P=0.024), postoperative distant metastasis (P<0.001), and TDs (P<0.001) were independent risk factors for long-term survival after rectal cancer surgery. Lymph node metastasis (P<0.001) and neoadjuvant therapy (P=0.023) were independent risk factors for the presence or absence of TDs of rectal cancer. In the non-neoassisted subgroup, postoperative distant metastasis (P<0.001) was considered to be an independent risk factor for long-term survival after rectal cancer surgery. Conclusions: In the under the peritoneal reflection group, the combination of mrEMVI and TDs seems to play a certain guiding role in predicting distant metastasis and long-term survival after rectal cancer surgery.

A new nomogram for assessing complete response (CR) in gastric diffuse large B-cell lymphoma (DLBCL) patients after chemotherapy.

PURPOSE: Achieving complete response (CR) after first-line chemotherapy in gastric DLBCL patients often results in longer disease-free survival. We explored whether a model based on imaging features combined with clinicopathological factors could assess the CR to chemotherapy in patients with gastric DLBCL. METHODS: Univariate (P < 0.10) and multivariate (P < 0.05) analyses were used to identify factors associated with a CR to treatment. As a result, a system was developed to evaluate whether gastric DLBCL patients had a CR to chemotherapy. Evidence was found to support the model's ability to predict outcomes and demonstrate clinical value. RESULTS: We retrospectively analysed 108 people who had been diagnosed gastric DLBCL; 53 were in CR. Patients were divided at random into a 5:4 training/testing dataset split. ß2 microglobulin before and after chemotherapy and lesion length after chemotherapy were independent predictors of the CR of gastric DLBCL patients after chemotherapy. These factors were used in the predictive model construction. In the training dataset, the area under the curve (AUC) of the model was 0.929, the specificity was 0.806, and the sensitivity was 0.862. In the testing dataset, the model had an AUC of 0.957, specificity of 0.792, and sensitivity of 0.958. The AUC did not differ significantly between the training and testing dates (P > 0.05). CONCLUSION: A model constructed using imaging features combined with clinicopathological factors could effectively evaluate the CR to chemotherapy in gastric DLBCL patients. The predictive model can facilitate the monitoring of patients and be used to adjust individualised treatment plans.