Synergistic effect of PARP inhibitor and BRD4 inhibitor in multiple models of ovarian cancer.

Ovarian cancer has the highest facility rate among gynaecological tumours. Current therapies including PARP inhibitors have a defect that ovarian tumour is easy to recurrent and become resistant to therapy. To solve this problem, we found that BRD4 inhibitor AZD5153 and PARP inhibitor olaparib had a widespread synergistic effect in multiple models with different gene backgrounds.

Mutation profiles in circulating cell-free DNA predict acquired resistance to olaparib in high-grade serous ovarian carcinoma.

Although resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) has gradually become a major challenge in the maintenance therapy for high-grade serous ovarian carcinoma (HGSOC), there are no universal indicators for resistance monitoring in patients. A key resistance mechanism to PARPi is the restoration of homologous recombination repair (HRR), including BRCA reversion mutations and changes in DNA damage repair proteins. To explore mutation profiles associated with PARPi resistance, we undertook targeted 42-gene deep sequencing of circulating cell-free DNA (cfDNA) extracted from HGSOC patients pre- and post-treatment with olaparib maintenance therapy.

Inhibiting the IRE1α Axis of the Unfolded Protein Response Enhances the Antitumor Effect of AZD1775 in TP53 Mutant Ovarian Cancer.

Targeting the G2/M checkpoint mediator WEE1 has been explored as a novel treatment strategy in ovarian cancer, but mechanisms underlying its efficacy and resistance remains to be understood. Here, it is demonstrated that the WEE1 inhibitor AZD1775 induces endoplasmic reticulum stress and activates the protein kinase RNA-like ER kinase (PERK) and inositol-required enzyme 1α (IRE1α) branches of the unfolded protein response (UPR) in TP53 mutant (mtTP53) ovarian cancer models. This is facilitated through NF-κB mediated senescence-associated secretory phenotype.

Phenolic Contents, Organic Acids, and the Antioxidant and Bio Activity of Wild Medicinal Berberis Plants- as Sustainable Sources of Functional Food.

Wild fruits have increasingly been investigated as part of recent searches for food products with a high antioxidant activity. In this study, wild edible berberis collected from three different provinces (Jilin, Heilongjiang, and Liaoning) were investigated for their phenolic contents, organic acid contents, mineral contents, antioxidant activity as well as their antimicrobial potential against a range of common food borne pathogens. In addition, a physiochemical and mineral analysis of the fruits was also performed.

The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer.

Background: Ovarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear.

AZD5153 reverses palbociclib resistance in ovarian cancer by inhibiting cell cycle-related proteins and the MAPK/PI3K-AKT pathway.

The CDK4/6 inhibitor, palbociclib has recently entered clinic-trial stage for breast cancer treatment. However, translating its efficacy to other solid tumors has been challenging, especially for aggressive solid tumors. We found that the effect of palbociclib as a single agent was limited due to primary and acquired resistance in multiple ovarian cancer (OC) models.

Impact of chemotherapy and immunotherapy on the composition and function of immune cells in COVID-19 convalescent with gynecological tumors.

Ongoing pandemic and potential resurgence of Coronavirus disease 2019 (COVID-19) has prompted urgent efforts to investigate the immunological memory of convalescent patients, especially in patients with active cancers. Here we performed single-cell RNA sequencing in peripheral blood samples of 3 healthy donors (HDs), 4 COVID-19 patients (Covs) and 4 COVID-19 patients with active gynecological tumor (TCs) pre- and post- anti-tumor treatment. All Covs patients had recovered from their acute infection.

WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway.

Targeted therapies represent attractive combination partners with immune checkpoint blockade (ICB) to increase the population of patients who benefit or to interdict the emergence of resistance. We demonstrate that targeting WEE1 up-regulates immune signaling through the double-stranded RNA (dsRNA) viral defense pathway with subsequent responsiveness to immune checkpoint blockade even in cGAS/STING-deficient tumors, which is a typical phenotype across multiple cancer types. WEE1 inhibition increases endogenous retroviral elements (ERVs) expression by relieving SETDB1/H3K9me3 repression through down-regulating FOXM1.

New Ln-MOFs based on mixed organic ligands: synthesis, structure and efficient luminescence sensing of the Hg ions in aqueous solutions.

In view of Hg ion sensing by luminescence, a series of new, phenanthroline-decorated 3D lanthanide metal organic frameworks (Ln-MOFs) valorising an original combination of four different lanthanides and two organic ligands, thiobis(4-methylene-benzoic acid) (Htmba) and 1,10-phenanthroline (phen), have been successfully synthesized, namely {[Ln(tmba)(phen)]·(HO)(phen)} [Ln = Ce, = 3 (1); Pr, = 1 (2); Eu, = 3 (3); and Tb, = 3 (4)]. Compounds 1-4 were characterised by single-crystal X-ray diffraction, elemental and thermogravimetric analyses, and powder X-ray diffraction. The luminescence properties of complexes 3 and 4 were thoroughly investigated.

Trends and age-period-cohort effects on mortality of the three major gynecologic cancers in China from 1990 to 2019: Cervical, ovarian and uterine cancer.

Background: Gynecologic cancers seriously threaten women's life and health. This study aims to assess the long-term trends of mortality from the three major gynecologic cancers in China and to examine the age-, period-, and cohort-specific effects behind them during the period 1990 to 2019.

Methods: The mortality data of cervical, ovarian, and uterine cancer in China were obtained from the Global Burden of Disease Study 2019 and were analyzed with the age-period-cohort framework.

The Diversity of Vaginal Microbiota Predicts Neoadjuvant Chemotherapy Responsiveness in Locally Advanced Cervical Cancer.

The vaginal microbiota is closely related to HPV infection and cervical cancer (CC), but its relationship with platinum-based chemotherapy responsiveness is unknown. The study aimed to investigate the vaginal microbiota diversity of women with locally advanced cervical cancer (LACC) and compare the differences between responders and nonresponders. We characterized the 16S rRNA gene sequencing of vaginal microbiome of 66 vaginal samples, including 26 LACC patients before neoadjuvant chemotherapy and 40 healthy controls.

Clinical and molecular characteristics of COVID-19 patients with persistent SARS-CoV-2 infection.

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Here, we compare the clinical and molecular features of patients with long duration of viral shedding (LDs) with those from patients with short duration patients (SDs), and healthy donors (HDs). We find that several cytokines and chemokines, such as interleukin (IL)-2, tumor necrosis factor (TNF) and lymphotoxin α (LT-α) are present at lower levels in LDs than SDs.

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19 : A Retrospective Study.

Background: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited.

Objective: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity.

Design: Retrospective cohort study.

Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endometrial carcinoma.

Background: Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Histopathological risk stratification lacks reproducibility, neglects heterogeneity and contributes little to surgical procedures. Existing molecular stratification is useless in patients with specific pathological or molecular characteristics and cannot guide postoperative adjuvant radiotherapies.

Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis.

Background: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19.

Methods: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias.

Striking dual functionality of a novel Pd@Eu-MOF nanocatalyst in C(sp)-C(sp) bond-forming and CO fixation reactions.

Pd nanoparticles were immobilized on a highly porous, hydrothermally stable Eu-MOF via solution impregnation and H2 reduction to yield a novel Pd@Eu-MOF nanocatalyst. This composite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), inductively coupled plasma optical emission spectroscopy (ICP-OES), powder X-ray diffraction (PXRD) and X-ray photoelectron spectroscopy (XPS). Unprecedentedly, the Pd@Eu-MOF nanocatalyst could be applied with excellent results in two strikingly different, mechanistically distinct, reactions i.

Pathogenic Effects and Potential Regulatory Mechanisms of Tea Polyphenols on Obesity.

Overweight and obesity are major threats to human health. Tea polyphenols exert multiple beneficial effects on human health and may play a positive regulatory role in fat assumption. However, how tea polyphenols contribute to the regulation of fat metabolism remains unclear to date.

Tailoring the structure, pH sensitivity and catalytic performance in Suzuki-Miyaura cross-couplings of Ln/Pd MOFs based on the 1,1'-di(p-carboxybenzyl)-2,2'-diimidazole linker.

An array of heterobimetallic Pd/Ln MOFs (1-4) with Sm, Eu, Tb, Dy as preferred metal nodes and 1,1'-di(p-carboxybenzyl)-2,2'-diimidazole (H2L) as a fairly suitable bifunctional organic linker have been synthesized, fully characterized and tested as catalysts in cross-coupling reactions. These robust MOFs, ensuring a uniform distribution of Pd, showed excellent stability in air and high catalytic activity in Suzuki-Miyaura reactions conducted in neat water, neat ethanol as well as water-ethanol mixture. Depending on the solvent, complex 1 could be effectively recycled 4-8 times without significant loss of catalytic activity.

A Yellow-Emitting Homoleptic Iridium(III) Complex Constructed from a Multifunctional Spiro Ligand for Highly Efficient Phosphorescent Organic Light-Emitting Diodes.

To suppress concentration quenching and to improve charge-carrier injection/transport in the emission layer (EML) of phosphorescent organic light-emitting diodes (PhOLEDs), a facial homoleptic iridium(III) complex emitter with amorphous characteristics was designed and prepared in one step from a multifunctional spiro ligand containing spiro[fluorene-9,9'-xanthene] (SFX) unit. Single-crystal X-ray analysis of the resulting fac-Ir(SFXpy) complex revealed an enlarged Ir···Ir distance and negligible intermolecular π-π interactions between the spiro ligands. The emitter exhibits yellow emission and almost equal energy levels compared to the commercial phosphor iridium(III) bis(4-phenylthieno[3,2-c]pyridinato-N,C')acetylacetonate (PO-01).

The synergistic effect of cobalt on a Pd/Co catalyzed Suzuki-Miyaura cross-coupling in water.

This work introduces the new trimetallic complex CoPd(HBPDC)Cl·(HO)(HBPDC = 2,2'-bipyridine-4,4'-dicarboxylic acid) as a highly efficient and more cost-effective catalyst for a Suzuki-Miyaura reaction proceeding in water, without additives and under aerobic conditions. Catalytic studies revealed a synergistic Co-Pd cooperativity, fostered by ligation through HBPDC, and accounting for the superior performance of the heterobimetallic complex vs. its Co-free counterpart.

Novel mononuclear Pt and Pd complexes containing (2,3-f)pyrazino(1,10)phenanthroline-2,3-dicarboxylic acid as a multi-donor ligand. Synthesis, structure, interaction with DNA, in vitro cytotoxicity, and apoptosis.

New cytotoxic, mononuclear Pt and Pd coordination complexes featuring the planar, multi-donor ligand (2,3-f)pyrazino(1,10)phenanthroline-2,3-dicarboxylic acid (HPPDA) have been synthesized under hydrothermal conditions (in water, at high temperature and pressure) and fully characterized. The complexes were proven to be isostructural by applying the single-crystal X-ray diffraction technique. UV-Vis and fluorescence spectroscopy investigations on their interaction with fish sperm DNA revealed a considerable binding capacity while gel electrophoresis provided evidence in favor of cleavage of pBR322 plasmid DNA.

Facile synthesis and luminescence properties of Y2O3:Ln(3+) (Ln(3+) = Eu(3+), Tb(3+), Dy(3+), Sm(3+), Er(3+), Ho(3+), Tm(3+), Yb(3+)/Er(3+), Yb(3+)/Tm(3+), Yb(3+)/Ho(3+)) microspheres.

Multicolor and monodisperse Y2O3:Ln(3+) (Ln(3+) = Eu(3+), Tb(3+), Dy(3+), Sm(3+), Er(3+), Ho(3+), Tm(3+), Yb(3+)/Er(3+), Yb(3+)/Ho(3+)) microspheres were prepared through a facile urea-assisted homogeneous precipitation method followed by a subsequent calcination process. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectrum (EDS), Fourier transformed infrared (FT-IR), thermogravimetric analysis (TGA), photoluminescence (PL) and cathodoluminescence (CL) spectra were employed to characterize the samples. The XRD results reveal that the as-prepared spheres can be well indexed to cubic Y2O3 phase with high purity.

Synthesis, structure and properties of 2D lanthanide coordination polymers based on N-heterocyclic arylpolycarboxylate ligands.

The reaction of 3-(2,4-dicarboxyphenyl)-2,6-pyridinedicarboxylic acid (H4dppd) with rare earth nitrates under hydrothermal conditions generated a series of new two-dimensional (2D) coordination polymers, namely {[La(Hdppd)(H2O)2·(H2O)2]n (1), [Ln2(Hdppd)2(H2O)4·(H2O)3]n [Ln = Sm (2), Eu (3)] and [Ln(Hdppd)(H2O)3·H2O]n [Ln = Gd (4), Tb (5), Dy (6), Ho (7), Er (8)] [Hdppd = 3-(2,4-dicarboxyphenyl)-2,6-pyridinedicarboxylic trivalent anion]}. The complexes were characterized by X-ray single-crystal diffraction, infrared spectroscopy, elemental analysis and thermogravimetric analysis. Luminescence spectroscopy of 3 and 5 showed bright red and green luminescences due to the 4f(n)-4f(n) transitions in Eu(3+) and Tb(3+) respectively, although the luminescence lifetime is shortened by non-radiative decay due to the presence of coordinating water molecules.