C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer.

Although Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved in multiple diseases, including BRCA1/2 mutant breast cancer, responses are usually transient requiring the deployment of combination therapies for optimal efficacy. Here we thus explore mechanisms underlying sensitivity and resistance to PARPi using two intrinsically PARPi sensitive (T22) and resistant (T127) syngeneic murine breast cancer models in female mice. We demonstrate that tumor associated macrophages (TAM) potentially contribute to the differential sensitivity to PARPi.

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1.

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study.

Introduction: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China.

Materials And Methods: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status.

Modulating the d-Band Center of RuO via Ni Incorporation for Efficient and Durable Li-O batteries.

Rechargeable Li-O batteries (LOBs) are considered as one of the most promising candidates for new-generation energy storage devices. One of major impediments is the poor cycle stability derived from the sluggish reaction kinetics of unreliable cathode catalysts, hindering the commercial application of LOBs. Therefore, the rational design of efficient and durable catalysts is critical for LOBs.

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation.

Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes.

Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer.

Background: Immunotherapy favors patients with tumors; however, only 3-26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial.

A Promising New Model: Establishment of Patient-Derived Organoid Models Covering HPV-Related Cervical Pre-Cancerous Lesions and Their Cancers.

The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established.

Psoralen synergies with zinc implants to promote bone repair by regulating ZIP4 in rats with bone defect.

Background: The regulation of dose-dependent biological effects induced by biodegradation is a challenge for the production of biodegradable bone-substitute materials, especially biodegradable zinc (Zn) -based materials. Cytotoxicity caused by excess local Zn ions (Zn) from degradation is one of the factors limiting the wide application of Zn implants. Given that previous studies have revealed that delayed degradation of Zn materials by surface modification does not reduce cytotoxicity; in the present study, we explore whether preventing the entry of excess Zn into cells may can reduce local Zn toxicity by applying Psoralen (PRL) to Zn implants and assessing its ability to regulate intracellular Zn concentrations.

Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

Background: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer.

Inhibition of SF3B1 improves the immune microenvironment through pyroptosis and synergizes with αPDL1 in ovarian cancer.

Ovarian cancer is resistant to immune checkpoint blockade (ICB) treatment. Combination of targeted therapy and immunotherapy is a promising strategy for ovarian cancer treatment benefit from an improved immune microenvironment. In this study, Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) cohorts were used to screen prognosis and cytotoxic lymphocyte infiltration-associated genes in upregulated genes of ovarian cancer, tissue microarrays were built for further verification.

Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance.

Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial senescence), recapitulating different stages of squamous differentiation, showed distinct tumor immune microenvironments.

A Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro.

MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC.

Background: Although the clinical application of PARP inhibitors has brought hope to ovarian cancer, the problem of its resistance has become increasingly prominent. Therefore, clinical experts have been focused on finding specific indicators and therapeutic targets that can be used for resistance monitoring of PARP inhibitors.

Results: By cfDNA detecting during Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer, we found the presence of MRE11:p.

Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states.

Bromo- and extra-terminal domain (BET) inhibitors (BETi) have been shown to decrease tumor growth in preclinical models and clinical trials. However, toxicity and rapid emergence of resistance have limited their clinical implementation. To identify state changes underlying acquisition of resistance to the JQ1 BETi, we reanalyzed single-cell RNAseq data from JQ1 sensitive and resistant SUM149 and SUM159 triple-negative breast cancer cell lines.

Immunodiagnosis - the promise of personalized immunotherapy.

Immunotherapy showed remarkable efficacy in several cancer types. However, the majority of patients do not benefit from immunotherapy. Evaluating tumor heterogeneity and immune status before treatment is key to identifying patients that are more likely to respond to immunotherapy.

Prognostic significance of positive peritoneal cytology in endometrial carcinoma based on ESGO/ESTRO/ESP risk classification: A multicenter retrospective study.

Objective: This study aimed to determine the prognostic significance of positive peritoneal cytology (PC) on endometrial carcinoma (EC) patients under the ESGO/ESTRO/ESP risk classification.

Methods: This study retrospectively analyzed EC patients from 27 medical centers in China from 2000 to 2019. Patients were divided into three ESGO risk groups: low-risk, intermediate-risk and high-intermediate risk, and high-risk groups.

Determination of vitamin K in infant formulas by liquid chromatography-online electrochemical reduction based on porous Pt/Ti electrode-fluorescence detection.

A highly sensitive and selective HPLC method for the determination of vitamin K vitamers including phylloquinone (PK) and menaquinones (MK-4) in infant formulas is described. The K vitamers were quantified with a fluorescence detector after online post-column electrochemical reduction occurring in a laboratory-made electrochemical reactor (ECR) equipped with platinum plated porous titanium (Pt/Ti) electrodes. The morphology of the electrode showed that the grain size of Pt was homogeneous and well plated on the porous Ti substrate, resulting in largely improved electrochemical reduction efficiency due to the large specific surface area.

Factors driving the implementation of the 'Local New Year' policy to prevent COVID-19 in China.

This study examines the contradiction caused by the 'local new year' policy, that is, the conflict between the pandemic prevention policies and people's emotional demands during the Spring Festival, based on the normalisation of pandemic prevention and control. It focuses on the scientific logical relationship with the contradiction that people voluntarily support 'local new year', to explore the primary driving factors of their willingness. By evaluating the migrant workers in large cities, the primary influencing factors were screened, and the primary dynamic factors and their relationship were obtained using the Logit logical selection model and maximum-likelihood estimation.

, a potential predictor of prognosis, promotes CD8 T‑cell infiltration in ovarian serous carcinoma by inducing CCL5 secretion.

Ovarian serous carcinoma (OC) is a common cause of mortality among gynecological malignancies. Although tumor‑infiltrating CD8 T cells are associated with a favorable prognosis of OC, the underlying mechanisms are not clearly understood. The present study identified the key genes and potential molecular mechanisms associated with CD8 T‑cell infiltration in OC.