Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

A single NLR gene confers resistance to leaf and stripe rust in wheat.

Nucleotide-binding leucine-rich repeat (NLR) disease resistance genes typically confer resistance against races of a single pathogen. Here, we report that Yr87/Lr85, an NLR gene from Aegilops sharonensis and Aegilops longissima, confers resistance against both P. striiformis tritici (Pst) and Puccinia triticina (Pt) that cause stripe and leaf rust, respectively.

Temporal Trends in Patient Characteristics and Clinical Outcomes of TAVR: Over a Decade of Practice.

Transcatheter aortic valve replacement (TAVR) is indicated for severe aortic stenosis patients with a prohibitive surgical risk. However, its use has been expanding in recent years to include intermediate- and low-risk patients. Thus, registry data describing changes in patient characteristics and outcomes are needed.

A cub and sushi domain-containing protein with esterase-like activity confers insecticide resistance in the Indian malaria vector Anopheles stephensi.

Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting Insecticidal Nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we identified a previously uncharacterized- Cub and Sushi Domain containing Insecticide Resistance (CSDIR) protein and generated evidence for its role in mediating insecticide resistance in the Anopheles stephensi.

Origin and evolution of the bread wheat D genome.

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared with its wild ancestors, modern bread wheat shows lower genetic diversity, caused by polyploidisation, domestication and breeding bottlenecks. Wild wheat relatives represent genetic reservoirs, and harbour diversity and beneficial alleles that have not been incorporated into bread wheat.

Diagnostic accuracy and characteristics of symptomatic versus asymptomatic retained products of conception: A retrospective cohort study.

Objective: To assess the accuracy of diagnosing retained products of conception (RPOC) in symptomatic versus asymptomatic women, and to identify potential divergent ultrasound features between these groups.

Methods: This retrospective study included women aged 17-50 years who underwent hysteroscopy for suspected RPOC during 2018-2021. Clinical and sonographic data were analyzed, and multivariable linear regression models employed, to examine correlations between RPOC and sonographic findings, and to compare diagnostic accuracy between symptomatic and asymptomatic women.

Interstitial heterotopic pregnancy after bilateral total salpingectomy in IVF patients: a case report and literature review.

Objectives: Heterotopic pregnancy of an intrauterine pregnancy and an interstitial or stump pregnancy after bilateral salpingectomy is a rare complication of in vitro fertilization (IVF) that can lead to severe hemorrhage; prompt identification and management are important. The aim of this paper was to present a case report and an updated literature review of women who had had combined interstitial/stump and intrauterine pregnancies during an in an IVF cycle after total bilateral salpingectomy.

Material And Methods: We conducted a search in PubMed for reported heterotopic pregnancy, of a combined intrauterine pregnancy with an interstitial or stump pregnancy, in women who underwent IVF after bilateral salpingectomy.

In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia.

Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias.

Ethnic disparities in complete and partial molar pregnancy incidence: a retrospective analysis of arab and jewish women in single medical center.

Background: Molar pregnancies, encompassing complete and partial moles, represent a rare and enigmatic gestational disorder with potential ethnic variations in incidence. This study aimed to investigate relations of ethnicity with risks of complete and partial molar pregnancies within an Israeli population while accounting for age differences.

Methods: A retrospective study was conducted of data recorded during 2007-2021 in an academic medical center in Israel.

A 12.4-day periodicity in a close binary system after a supernova.

Neutron stars and stellar-mass black holes are the remnants of massive star explosions. Most massive stars reside in close binary systems, and the interplay between the companion star and the newly formed compact object has been theoretically explored, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.

Wheat fungal endophyte communities are inseparable from the host and influence plant development.

Plants harbor complex and highly diverse fungal endophyte communities (FECs), making it difficult to evaluate the functional role of individual taxa, subsets of the community, or the FEC as a whole. To reduce the complexity of this system, we aimed to produce fungi-null wheat () plants. To this end, we treated seeds with heat and fungicides and generated plants from rescued embryos and callus tissue.

Detection and dissection of sentinel nodes in endometrial endometrioid cancer with indocyanine green using PinPoint laparoscopy: Analysis of the learning curve.

Objective: Early-stage endometrial endometrioid adenocarcinoma is managed through laparoscopic total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Detection of positive nodes is rare, and lymphadenectomy may involve complications. Pelvic sentinel lymph node dissection can prevent complete dissection.

The Botrytis cinerea transglycosylase BcCrh4 is a cell death-inducing protein with cell death-promoting and -suppressing domains.

Botrytis cinerea is a necrotrophic fungal plant pathogen that causes grey mould and rot diseases in many crops. Here, we show that the B. cinerea BcCrh4 transglycosylase is secreted during plant infection and induces plant cell death and pattern-triggered immunity (PTI), fulfilling the characteristics of a cell death-inducing protein (CDIP).

Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients.

Background: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease.

Objective: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients.

Methods: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI.

Genome-wide association mapping of rust resistance in .

The rust diseases, including leaf rust caused by (), stem rust caused by f. sp. (), and stripe rust caused by f.

Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1.

Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells.

Serine peptidases and increased amounts of soluble proteins contribute to heat priming of the plant pathogenic fungus .

causes gray mold disease in leading crop plants. The disease develops only at cool temperatures, but the fungus remains viable in warm climates and can survive periods of extreme heat. We discovered a strong heat priming effect in which the exposure of to moderately high temperatures greatly improves its ability to cope with subsequent, potentially lethal temperature conditions.

The wheat stem rust resistance gene Sr43 encodes an unusual protein kinase.

To safeguard bread wheat against pests and diseases, breeders have introduced over 200 resistance genes into its genome, thus nearly doubling the number of designated resistance genes in the wheat gene pool. Isolating these genes facilitates their fast-tracking in breeding programs and incorporation into polygene stacks for more durable resistance. We cloned the stem rust resistance gene Sr43, which was crossed into bread wheat from the wild grass Thinopyrum elongatum.

Nonelectric shaving of endometrial polyp by hysteroscopy - A new technique to eliminate thermal damage.

Objective: To present a new technique for complete endometrial polypectomy, using the bipolar loop hysteroscope, but without the activation of electrical energy, and follow its efficiency and safety for the patient.

Study Design: This is a prospective descriptive study conducted at a university hospital. Forty four patients were recruited to the study according to an intra uterine polyp diagnosed by transvaginal ultrasound (TVS).

Alternative beta-hCG follow-up protocols after single-dose methotrexate therapy for ectopic pregnancy: A retrospective cohort study.

Objective: This study assessed the relevance of reductions in beta-hCG levels between days 0 and 4 and between days 0 and 7 after single-dose methotrexate therapy, and the success of the therapy.

Study Design: A retrospective cohort study of 276 women diagnosed with ectopic pregnancy who received methotrexate as first-line treatment. Demographics, sonographic findings and beta-hCG levels and indexes were compared between women with successful and failed treatment outcomes.

Significantly reduced inflammatory foreign-body-response to neuroimplants and improved recording performance in young compared to adult rats.

The multicellular inflammatory encapsulation of implanted intracortical multielectrode arrays (MEA) is associated with severe deterioration of their field potentials' (FP) recording performance, which thus limits the use of brain implants in basic research and clinical applications. Therefore, extensive efforts have been made to identify the conditions in which the inflammatory foreign body response (FBR) is alleviated, or to develop methods to mitigate the formation of the inflammatory barrier. Here, for the first time, we show that (1) in young rats (74±8 gr, 4 weeks old at the onset of the experiments), cortical tissue recovery following MEA implantation proceeds with ameliorated inflammatory scar as compared to adult rats (242 ± 18 gr, 9 weeks old at the experimental onset); (2) in contrast to adult rats in which the Colony Stimulating factor 1 Receptor (CSF1R) antagonist chow eliminated ∼95% of the cortical microglia but not microglia adhering to the implant surfaces, in young rats the microglia adhering to the implant were eliminated along with the parenchymal microglia population.

Botrytis cinerea Transcription Factor BcXyr1 Regulates (Hemi-)Cellulase Production and Fungal Virulence.

Botrytis cinerea is an agriculturally notorious plant-pathogenic fungus with a broad host range. During plant colonization, secretes a wide range of plant-cell-wall-degrading enzymes (PCWDEs) that help in macerating the plant tissue, but their role in pathogenicity has been unclear. Here, we report on the identification of a transcription factor, BcXyr1, that regulates the production of (hemi-)cellulases and is necessary for fungal virulence.