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Globally, most high-grade ores have already been exploited. Contemporary mining tends to focus on the extraction of lower-grade ores thereby leaving large stored tailings open to the environment. As a result, current mines have emerged as hotspots for the migration of metal(loid)s and resistance genes, thereby potentially contributing to a looming public health crisis. Therefore, the management and remediation of tailings are the most challenging issues in environmental ecology. Bioremediation, a cost-effective solution for the treatment of multi-element mixed pollution (co-contamination), shows promise for the restoration of mine tailings. This review focuses on the bioremediation technologies developed to untangle the issues of non-ferrous metal mine tailings. These technologies address the environmental risks of multi-element exposure to the ecosystem and human health risks. It provides a review and comparison of current bioremediation technologies used to mineralize metal(loid)s. The role of plant-microorganisms and their mechanisms in the remediation of tailings are also discussed. The importance of "treating waste with wastes" is crucial for advancing bioremediation technologies. This approach underscores the potential for waste materials to contribute to environmental cleanup processes. The concept of a circular economy is pertinent in this context, emphasizing recycling and reuse. There's an immediate need for international collaboration. Collaboration is needed in policy-making, funding, and data accessibility. Sharing data is essential for the growth of bioremediation globally. [Display omitted] • Co-contamination of tailings has caused catastrophic impacts on the ecological environment. • Mechanisms and field applications of remediation technologies are discussed. • Specialized methods for environmental risk assessment targeted at tailings are needed. • Bioremediation requires oversight to manage risks in challenging tailings. • Combined bioremediation technology coupled with wastes holds great potential for application. [ABSTRACT FROM AUTHOR]

[Display omitted] The development of the effective diagnostic method for the determination of cancer biomarkers is one of the most promising strategies for early clinical diagnosis of cancer. Here, based on the preparation of heterogeneous cuprous oxide coated silver (Ag@Cu 2 O) nanocomposites/graphitic carbon nitride (g-C 3 N 4)/cadmium sulfide (CdS) nanoarrays structure, a highly sensitive photoelectrochemical (PEC) biosensor for the examination of carcinoembryonic antigen (CEA) has been constructed successfully. The combination of photoactive semiconductor materials g-C 3 N 4 and CdS increases the electron transfer rate between them and enhances their photocurrent response, thus greatly increasing the concentration detection range. At the same time, the specific recognition between antigen and antibody is used to form a sandwich structure secondary antibody (Ab 2)/CEA/antibody (Ab 1). And because Ag@Cu 2 O has the function of absorbing light and consuming electron donor. Therefore, the successful measurement of CEA was achieved by labeling Ag@Cu 2 O on Ab 2 and finally immobilizing it on the sensor to correlate the current reduction with the CEA concentration. The sandwich PEC biosensor proposed by this signal amplification strategy under optimal conditions has good analytical performance for CEA, with a wide linear detection range (from 10-5 to 1 ng/mL) and a low detection limit of 0.0011 pg/mL. The PEC biosensor constructed by this method showed high sensitivity, excellent anti-interference ability, favourable repeatability, and good stability. [ABSTRACT FROM AUTHOR]

Acid mine drainage (AMD) caused environmental risks from heavy metal pollution, requiring treatment methods such as chemical precipitation and biological treatment. Monitoring and adapting treatment processes was crucial for success, but cost-effective pollution monitoring methods were lacking. Using bioindicators measured through 16S rRNA was a promising method to assess environmental pollution. This study evaluated the effects of AMD on ecological health using the ecological risk index (RI) and the Risk Assessment Code (RAC) indices. Additionally, we also examined how acidic metal stress affected the diversity of bacteria and fungi, as well as their networks. Bioindicators were identified using linear discriminant analysis effect size (LEfSe), Partial least squares regression (PLS-R), and Spearman analyses. The study found that Cd, Cu, Pb, and As pose potential ecological risks in that order. Fungal diversity decreased by 44.88% in AMD-affected areas, more than the 33.61% decrease in bacterial diversity. Microbial diversity was positively correlated with pH (r = 0.88, p = 0.04) and negatively correlated with bioavailable metal concentrations (r = −0.59, p = 0.05). Similarly, microbial diversity was negatively correlated with bioavailable metal concentrations (bio_Cu, bio_Pb, bio_Cd) (r = 0.79, p = 0.03). Acidiferrobacter and Thermoplasmataceae were prevalent in acidic metal environments, while Puia and Chitinophagaceae were identified as biomarker species in the control area (LDA>4). Acidiferrobacter and Thermoplasmataceae were found to be pH-tolerant bioindicators with high reliability (r = 1, P < 0.05, BW > 0.1) through PLS-R and Spearman analysis. Conversely, Puia and Chitinophagaceae were pH-sensitive bioindicators, while Teratosphaeriaceae was a potential bioindicator for Cu–Zn–Cd metal pollution. This study identified bioindicator species for acid and metal pollution in AMD habitats. This study outlined the focus of biological monitoring in AMD acidic stress environments, including extreme pH, heavy metal pollutants, and indicator species. It also provided essential information for heavy metal bioremediation, such as the role of omics and the effects of organic matter on metal bioavailability. [Display omitted] • The order of ecological risk for sources of AMD pollution had been determined to be Cd > Cu > Pb > As. • Three acid indicator species and one bioindicator species for heavy metals were screened. • A tool was provided to assess soil metal contamination and a screening model for bioindicators. [ABSTRACT FROM AUTHOR]

The quality of soil containing heavy metals (HMs) around nonferrous metal mining areas is often not favorable for plant growth. Three types of plant growth promoting rhizobacteria (PGPR)-assisted ryegrass were examined here to treat Cd, Pb, and Zn contaminated soil collected from a nonferrous metal smelting facility. The effects of PGPR-assisted plants on soil quality, plant growth, and the migration and transformation of HMs were evaluated. Results showed that inter-root inoculation of PGPR to ryegrass increased soil redox potential, urease, sucrase and acid phosphatase activities, microbial calorimetry, and bioavailable P, Si, and K content. Inoculation with PGPR also increased aboveground parts and root length, P, Si, and K contents, and antioxidant enzyme activities. The most significant effect was that the simultaneous inoculation of all three PGPRs increased the ryegrass extraction (%) of Cd (59.04–79.02), Pb (105.56–157.13), and Zn (27.71–40.79), compared to CK control (without fungi). Correspondingly, the inter-root soil contents (%) of total Cd (39.94–57.52), Pb (37.59–42.17), and Zn (34.05–37.28) were decreased compared to the CK1 control (without fungi and plants), whereas their bioavailability was increased. Results suggest that PGPR can improve soil quality in mining areas, promote plant growth, transform the fraction of HMs in soil, and increase the extraction of Cd, Pb, and Zn by ryegrass. PGPR is a promising microbe-assisted phytoremediation strategy that can promote the re-greening of vegetation in the mining area while remediating HMs pollution. [Display omitted] • Plant growth promoting rhizobacteria (PGPR) improves soil quality and plant growth. • PGPR increases the extraction of Cd, Pb and Zn by ryegrass. • PGPR works synergistically. [ABSTRACT FROM AUTHOR]

A series of goethite-modified montmorillonite (GMt) materials was synthesized for the amelioration of cationic cadmium (Cd) and anionic arsenic (As) complex contaminants in soil and water bodies. The results showed that goethite (Gt) was successfully loaded onto the surface of montmorillonite (Mt), which possessed more functional groups (such as Fe–O, and Fe–OH) and a larger specific surface area. GMt-0.5 (Mt loaded with Gt at a ratio of 0.5:1) showed the highest adsorption capacity for Cd(II) and As(III) with the maximum of 50.61 mg/g and 57.58 mg/g, respectively. The removal rate of Cd(II) was highly pH dependent, while the removal rate of As(III) showed little dependence on pH. The goethite on montmorillonite might contribute to the formation of surface complexes with As(III) and oxidation of As(III) to As(V). In the binary system, both, synergistic and competitive adsorption existed simultaneously. Importantly, in the binary system, the removal of As(III) was more favorable because of the electrostatic interaction, formation of a ternary complex, and co-precipitation. In addition, the amendment of GMt-0.5 significantly reduced the availability of Cd and As in the soil. This study suggests that GMt-0.5 is a promising candidate for the simultaneous immobilization of metal (loid)s in both, aqueous solution and mine soil. [Display omitted] • GMt-0.5 has a great removal efficiency for Cd(II) and As(III). • Higher adsorption capacity of GMt-0.5 for As(III) in both two systems. • In the binary system, Cd(II) remarkably enhanced the removal of As(III) by GMt-0.5. • Cd(II) induces As(III) to form ternary complexes and enhances As(III) adsorption. • GMt-0.5 effectively immobilizes Cd and As in mine soil. [ABSTRACT FROM AUTHOR]

• A load-balanced domain decomposition algorithm for 3D embedded unstructured grids. • Implementation of parallel simulations for embedded discrete fracture model. • Discussion on inter-processor communication patterns of embedded discrete fracture model. • Satisfactory scalability and parallel efficiency for a two-phase flow model with up 36 million grids on 1024 CPU cores. Recently, embedded discrete fracture model (EDFM) using non-conforming staggered 3D unstructured grids was presented for the numerical simulation of fluid-flows in large-scale complex fractured porous media. In this paper, we implement load-balanced parallel simulations for this approach on distributed memory systems. A load-balanced domain decomposition algorithm is presented to partition matrix grids and embedded fracture grids uniformly. We classify all grid connections on the boundary of subdomains to five types and illustrate corresponding inter-processor connections. A packaged inter-processor communication approach is implemented based on message passing interface (MPI) to improve communication efficiency for this simulation method. A two-phase parallel simulator is developed, and block coupled method is adopted to assemble the equations discretized in matrix and grid domains using two-point flux approximation (TPFA) finite volume method. The load-balanced algorithm is tested by nonuniformly distributed fracture networks. The performance and scalability are also tested on 1024 CPU cores by two complex fracture network models with up to 25 million matrix grids and 11 million embedded fracture grids. The results show satisfactory parallel efficiency and scalability. [ABSTRACT FROM AUTHOR]

• An improved embedded discrete fracture model for 3D unstructured grids. • Efficient and robust domain connectivity algorithms for 3D unstructured grids. • Block coupled solving method for overlapping matrix and fracture domains. • Tested for solving two-phase flow in a field-scale highly complex fracture network. Numerical simulation in 3D complex fractured media is challenging as the geometric discretization of porous media and fracture domains is on multiple scales. In this paper, we present an improved embedded discrete fracture model (EDFM) for 3D unstructured non-matching grids, and correspondingly efficient and robust domain connectivity algorithms are developed. Unlike traditional EDFM, improved EDFM is capable to simulate flows on 3D staggered overlapping unstructured matrix and fracture grids. We illustrate flux exchange patterns and formulas of improved EDFM. Two types of domain connectivity are built to assemble hybrid dimensional overlapping grids of matrix and fracture domains to a coupled linear system using finite volume method. Building domain connectivity is an important challenge for 3D hybrid-dimensional unstructured non-matching grids. We classify all points of domain connectivity into three types. A face indexed octree is employed for spatial binary search. Two types of grid adjacency information are used to accelerate the calculation of grid intersection points. Fracture-matrix intersection information is adopted to accelerate fracture-fracture connectivity generation. The performance of the algorithms is tested by 8 cases in different scales and compared with traversal method. Improved EDFM is validated against discrete fracture model and traditional EDFM using a two-phase flow solver. A case with highly complex fracture network is simulated to demonstrate the capacity of improved EDFM in real complex physical problems. The effects of grid type and resolution are also analyzed in this work. [ABSTRACT FROM AUTHOR]

[Display omitted] • In this study, MIL-101(Cr) was applied to nucleic acid adsorption and ATP detection. • The quenching mechanism of MIL-101(Cr) was studied deeply. • This strategy adopted aptamer/enzyme assisted cyclic amplification to promote ATP test. • Successfully designed the "AND" logic gate. With the development of frame materials, metal organic frameworks (MOFs) have been successfully applied in the fields of biological small molecule analysis and fluorescent DNA detection. In this work, in view of the good adsorption characteristics of MIL-101(Cr), the highly sensitive detection of adenosine triphosphate (ATP) assisted nucleic acid exonuclease amplification by MIL-101(Cr) on the different affinity of single stranded DNA and double stranded DNA was investigated. The detection limit of ATP reaches 1.7 μM, and the platform has good applicability in biological samples. On this basis, an "AND" logic gate was successfully constructed. Superior sensitivity to ATP in the presence of exonuclease was reflected, which greatly enhanced the system's fluorescence. Importantly, the fluorescence sensing application of this nanomaterial inspired other target detection and enriched the building blocks of fluorescence sensing platform. [ABSTRACT FROM AUTHOR]

Bacterium with high Cr(VI) detoxification capability belonged to the genus Bacillus have been largely explored, yet their reduction strategies are still in debate. Cr(VI) removal performance and mechanism of Bacillus sp. HL1 isolated from tailings a site was comprehensively investigated in this study. Approximately 88.31% of 100 mg/L Cr(VI) was continuously removed within 72 h, while it could resist up to 300 mg/L Cr(VI). Metal ions Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance to 14.41% and 3.41% under the optimal conditions, respectively. Cr(VI) removal performances by subcellular extracts showed that nearly 45.28% of 100 mg/L extracellular Cr(VI) was efficaciously reduced to Cr(III), while only 14.27%, 6.40%, and 2.73% of the cell-free extract, resting cells, and cell debris were reduced, respectively. This suggested that extracellular bioreduction was the primary Cr(VI) detoxification strategy despite a small part of Cr(VI) reduction took place intracellularly. In particular, the reduction products of the intracellular and extracellular compounds significantly differed, with organo-Cr(III) complex outside the cell and crystalline Cr(III) precipitate inside. Such observation was also evidenced by the intracellular black precipitate observed in the TEM image. XRD, XPS, and EPR analysis showed different Cr(III) compositions of intracellular and extracellular products. This study deepens our insights into the different fates of microorganisms that reduce Cr(VI) intracellularly and extracellularly. • Extracellular bioreduction was main Cr(VI) detoxification strategies by the newly isolated Bacillus sp. HL1. • Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance. • Extracellular organo-Cr(III) complex and intracellular crystalline Cr(III) precipitate were the main reduced products. [ABSTRACT FROM AUTHOR]

[Display omitted] Metal-organic polymers (MOPs) can enhance the photoelectrochemical (PEC) water oxidation performance of BiVO 4 photoanodes, but their PEC mechanisms have yet to be comprehended. In this work, we constructed an active and stable composite photoelectrode by overlaying a uniform MOP on the BiVO 4 surface using Fe2+ as the metal ions and 2,5-dihydroxyterephthalic acid (DHTA) as ligand. Such modification on the BiVO 4 surface yielded a core-shell structure that could effectively enhance the PEC water oxidation activity of the BiVO 4 photoanode. Our intensity-modulated photocurrent spectroscopy analysis revealed that the MOP overlayer could concurrently reduce the surface charge recombination rate constant (k sr) and enhance the charge transfer rate constant (k tr), thus accelerating water oxidation activity. These phenomena can be ascribed to the passivation of the surface that inhibits the recombination of the charge carrier and the MOP catalytic layer that improves the hole transfer. Our rate law analysis also demonstrated that the MOP coverage shifted the reaction order of the BiVO 4 photoanode from the third-order to the first-order, resulting in a more favorable rate-determining step where only one hole accumulation is required to overcome water oxidation. This work provides new insights into the reaction mechanism of MOP-modified semiconductor photoanodes. [ABSTRACT FROM AUTHOR]

The growing global demand for non-ferrous metals has led to serious environmental issues involving uncovered mine site slag dumps that threaten the surrounding soils, surface waters, groundwater, and the atmosphere. Remediation of these slags using substitute cement materials for ordinary Portland cement (OPC) and precursors for alkali-activated materials (AAMs) can convert hazardous solid wastes into valuable construction materials, as well as to attain the desired solidification and stabilization (S/S) of heavy metal(loid)s (HM). This review discusses the current research on the effect of non-ferrous slags on the reaction mechanisms of the OPC and AAM. The S/S of HM from the non-ferrous slags in AAM and OPC is also reviewed. HM can be stabilized in these materials based on the complex salt effect and isomorphic effects. The major challenges faced in AAMs and OPC for HM stabilization include the long-term durability of the matrix (e.g., sulfate attack, stability of volume). The existing knowledge gaps and future trends for the sustainable application of non-ferrous slags are also discussed. [Display omitted] • The effect of non-ferrous slags on reaction mechanisms of the OPC and AAM was discussed. • The S/S of HM from the non-ferrous slags in AAM and OPC were reviewed. • The long-term durability of the AAMs and OPC for HM stabilization were proposed. [ABSTRACT FROM AUTHOR]

GPRASP2 is implicated in nervous system diseases, tumors and immune inflammation. In our previous study, G protein-coupled receptor associated sorting protein 2 (GPRASP2) was identified as a novel causal gene for X-linked recessive syndromic hearing loss (SHL). However, the role of GPRASP2 in auditory function has not been elucidated. The Gprasp2 -knockout (KO) mouse HEI-OC1 auditory cells were constructed using CRISPR/Cas9-mediated gene editing. RNA-sequencing (RNA-seq) was used to investigate the differentially expressed genes (DEGs) and DEGs-enriched signaling pathways, which was verified by Western blot. Flow cytometry assay was used to examine cell apoptosis. The cytological pathology was evaluated by laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). Mitochondrial damage was observed in Gprasp2 -KO HEI-OC1 cells. RNA-seq analysis suggested that Gprasp2 -KO was implicated in the apoptosis process, which could be mediated by Hedgehog (Hh) signaling pathway. The key molecules in Hh signaling pathway (Smo, Gli1, Gli2) were detected to be down-regulated in Gprasp2 -KO HEI-OC1 cells. The differential expression of apoptosis molecules (Bcl2, Bax, Caspase-3/cleaved-Caspase-3) indicated that Gprasp2 -KO induced apoptosis in HEI-OC1 cells. The treatment of smoothened agonist (Purmorphamine, PUR) activated the Hh-Gli signaling pathway and reduced apoptosis in Gprasp2 -KO HEI-OC1 cells. This study revealed that Gprasp2 -disruption inhibited Hh signaling pathway and led to cell apoptosis in HEI-OC1 cells, which might provide the potential molecular mechanism of GPRASP2 mutation associated with human SHL. • Gprasp2 disruption induced mitochondrial damage and apoptosis in HEI-OC1 cells. • Gprasp2 disruption inhibited Hedgehog signaling pathway in HEI-OC1 cells. • The smoothened agonist could reduce apoptosis in Gprasp2 -knockout HEI-OC1 cells. [ABSTRACT FROM AUTHOR]

Objectives: It is well known that cancer patients with concurrent venous thromboembolism (VTE) have poorer oncologic outcomes. Even though 25-40% of ovarian cancer patients develop a VTE, the role of tumor-specific molecular factors in VTE development is not known. Therefore, we aimed to perform a comprehensive multi-platform omics analysis to identify factors in ovarian cancer that could be related to the development of VTE or the associated impact on patient outcomes. Methods: Patients diagnosed with high-grade serous ovarian carcinoma (HGSOC) between 2013 and 2019 with frozen tissue and matched germline blood samples available were screened for a concurrent diagnosis of VTE. We performed a multiplatform omics analysis, including bulk RNA sequencing (RNA-seq), proteomics, and DNA whole-exome sequencing (WES), followed by integrated analysis on a total of 32 patient samples (n =16, VTE; n =16, non-VTE as controls). Bioinformatics analyses were then carried out to identify potential molecular abnormalities that could contribute to the pathology of VTE in ovarian cancer. Results: The timing of VTE varied across the 16 cases of VTE, ranging from the onset at the time of diagnosis of ovarian cancer (n =9; 56%), during neoadjuvant chemotherapy (NACT; n =2, 12.5%), and within 28 days of surgery or during adjuvant chemotherapy (n =5; 31.3%). The average overall survival (OS) of patients with VTE was 2.05 years (SD: 1.35); however, OS for the control group could not be calculated since more than 80% (n =13, 81.3%) are still alive with the disease after a mean of 3.5 years (SD: 1.07). RNA-seq analysis revealed 130 differentially expressed genes in VTE versus control. Most notably, the F3 gene, which encodes tissue factors, was upregulated in nearly all VTE samples compared to controls. A Cox regression using age, grade, and gene expression indicated an association with worse overall survival for GAPDHP65 and NRSN2-AS1 with hazard ratios of >1.5 (p=0.018 and p<0.001, respectively). On proteomics analysis, we quantified over 7,300 proteins in VTE versus control, of which 255 were significantly altered (p<0.01). Principal component analysis showed that these altered proteins explained 47.5% of the variance between groups. They did not demonstrate a relationship with the onset of VTE timing, suggesting tumor-mediated changes independent of ovarian cancer treatment status. Among the significantly altered putative drug targets, we identified platelet-derived growth factor subunit B (PDGFB) elevated nearly tenfold in the VTE versus the control group. We also observed a profound trend of increased collagen 1A1 and 3A1 in the VTE group. The proteins elevated in the VTE group were biased towards an expression within the extracellular space. Integrated analyses with RNA-seq data indicate a strong correlation of protein and transcript abundance in 64 candidate proteins (Spearman Rho=0.677, p<0.0001). WES analysis revealed predominantly missense mutations in the form of single-nucleotidepolymorphisms (SNPs). Several distinct genes were mutated within the VTE cohort compared to the control group; however, these did not reach statistical significance, likely due to the small sample size. Conclusions: We provide the first multiplatform comprehensive multi-omics analysis of HGSOC based on VTE development. These findings suggest substantial molecular differences in tumors from patients who develop VTE compared to those that do not. These findings could have implications for risk stratification and preventative and treatment strategies for VTE. [ABSTRACT FROM AUTHOR]

As a susceptibility gene for human inflammatory bowel diseases (IBD), how avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) modulates intestinal mucosal immune response remains unclear. Here we studied the potential roles of ETS-1 in the pathogenesis of IBD. ETS-1 expression was examined in IBD patients. CD45RBhighCD4+ T cell-transfer colitis, dextran sulfate sodium (DSS)-induced colitis, and azomethane (AOM)/DSS-induced colitis-associated cancer (CAC) models were constructed to probe the function of ETS-1 in vivo. RNA-sequencing of CD4+ T cells from Ets-1 transgenic (Tg) mice was performed to decipher the key differentially expressed genes. Adenovirus transduction was conducted to verify the therapeutic potentials of ETS-1 in vivo. ETS-1 expression was significantly increased in CD4+ T cells from active IBD patients compared with healthy controls, which was upregulated by TNF-α but markedly suppressed by anti -TNF-α mAb therapy. More severe colitis was observed in Rag1 −/− mice reconstituted with Ets-1TgCD45RBhighCD4+ T cells or in Ets- 1 Tg mice after DSS exposure compared with controls, characterized by higher TNF-α and IFN-γ expression in inflamed colon. Ets- 1 Tg mice were more prone to develop AOM/DSS-induced CAC, and bone marrow chimeras further proved that lamina propria immune cells but not intestinal epithelial cells contributed to the development of colitis. RNA-sequencing and luciferase analysis revealed cold-inducible RNA-binding protein (CIRBP) as a functional target of ETS-1 to promote Th1 cell-driven immune response. Consistently, intraperitoneal administration of adenovirus-m- cirbp -shRNA ameliorated trinitrobenzene sulfonic acid (TNBS)-induced colitis of Ets- 1 Tg mice. Our data identify that ETS-1 is highly expressed in IBD patients and promotes Th1-driven mucosal inflammation through CIRBP. CIRBP may serve as a novel therapeutic target for treatment of human IBD. [Display omitted] • ETS-1 is highly expressed in CD4+ T cells of IBD patients and facilitates Th1 cell differentiation. • Overexpression of ETS-1 in CD4+ T cells promotes colitis and colitis-associated cancer in mice. • ETS-1 facilitates CIRBP expression to induce Th1 cell-associated intestinal inflammation. • Blockade of CIRBP ameliorates murine colitis and CIRBP may be a novel therapeutic approach in treatment of human IBD. [ABSTRACT FROM AUTHOR]

Despite similar histologic appearance amongst high-grade serous ovarian cancers (HGSOC), anecdotally there are differences in gross appearance. However, no systematic framework to classify morphologic differences exists. Therefore, we aimed to determine whether high-grade serous ovarian cancers (HGSOC) can be reliably divided into distinct gross morphologic subtypes and to assess clinical outcomes and molecular features of these subtypes. A retrospective review was performed of video-recordings from patients who underwent laparoscopic assessment of disease burden prior to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). Video recordings were reviewed by at least 2 physicians. A total of 4 sites (diaphragm, omentum, peritoneum, and pelvis) were assessed and classified as type I (deep, infiltrative disease with distortion of surrounding tissue) or type II (superficial, exophytic disease bordered by normal tissue). Tumor tissues from 16 of these chemotherapy-naïve patients were analyzed by multi-platform omics (RNA sequencing, proteomics). Clinical outcomes were assessed utilizing a prospectively collected database and compared by morphology using t-test or Fisher's exact test. Of the 99 evaluable patients, 60 exhibited uniform morphology at all involved metastatic sites (65% type I and 35% type II), and 81 exhibited a predominating morphology (58% type I and 42% type II). A total of 164 images were reviewed by a third physician with 83.5% inter-rater concordance (κ=0.6446). Patients with uniform type 1 (n=34)tumor morphology were more likely to exhibit an excellent response to NACT (defined as radiologic or CA-125 complete response) than those with type II (n=16) tumor morphology (47% vs 18%, p=0.13). Patients with type II predominant tumor morphology had a significantly higher estimated blood loss at the time of interval debulking surgery (p=0.008) as well as longer operative time (p=0.03) compared with type I tumor morphology. Patients with complete type II morphology were more likely to have a modified Fagotti score of <8 (p=0.026), and thus were more likely to be triaged to PDS. On histopathologic review of 7 type I cases and 4 type II cases, no obvious histo-pathological pattern dominated either type. We identified distinct molecular differences between the 2 types, including increased TGF-β expression in type I and increased MYC expression in type II. Type I tumors seem to have abundant stroma and are immunologically active, whereas type II tumors seem to be dominated by cancer cells, have little stroma, and are immunologically cold. There are at least two distinct gross morphological patterns of HGSOC with unique molecular differences and responses to chemotherapy. These findings could have major clinical implications for tailored therapeutic strategies. [Display omitted] [ABSTRACT FROM AUTHOR]