Dynamic Localization of Endoplasmic Reticulum during Tetrahymena Conjugation.

Changes in lipid composition at membrane fusion sites in mating Tetrahymena are thought to involve the endoplasmic reticulum (ER), but its localization to these sites has not been observed. Here we show ER distribution during Tetrahymena mating using TtRET1-GFP and GFP-KDEL. We find that both markers localize to perinuclear membranes and tubular structures that connect perinuclear membrane to plasma membrane at fusion sites.

Tumor integrin targeted theranostic iron oxide nanoparticles for delivery of caffeic acid phenethyl ester: preparation, characterization, and anti-myeloma activities.

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells preferentially in the bone marrow. Currently, emerging chemotherapy drugs with improved biosafety profiles, such as immunomodulatory agents and protease inhibitors, have been used in clinics to treat MM in both initial therapy or maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT). We previously discovered that caffeic acid phenethyl ester (CAPE), a water-insoluble natural compound, inhibited the growth of MM cells by inducing oxidative stress.

Variations in subpectoral biceps tenodesis locations do not impact clinical outcomes.

Background: Biceps tenodesis is a common treatment for pathologies involving the long head of the biceps brachii. Given variations in surgical approach, focus has been placed on the location of the tenodesis to maintain appropriate length-tension relationship. The purpose of this study is to assess for variations in the tunnel placement in subpectoral biceps tenodesis procedures and correlation of tunnel position with patient-reported outcomes.

FlaxPack: Tailored Natural Fiber Reinforced (NFRP) Compliant Folding Corrugation for Reversibly Deployable Bending-Active Curved Structures.

As the use of Natural Fiber Reinforced Polymers (NFRPs) become increasingly popular in the built environment, steps in established workflows, including molding and transportation, continue to impose constraints on what is possible in the material's fabrication process. This research builds on previous studies of moldless fiber composites using tailored fiber placement (TFP) as a fabrication method. By integrating compliant folding mechanisms into the flat preform to give shape to the final desired geometry this research replaces all dependencies on molds and formworks during the resin curing process with programmed formal deformations.

Off-label: The results of adjunctive bone morphogenetic protein for challenging femur fractures; a review of two cases.

Background: Although bone morphogenetic proteins (BMPs) are used as an adjunct to promote healing, they may have unintended effects such as heterotopic ossification (HO). The literature is limited regarding the effect of using off-label BMPs for femur fractures.

Case Presentation: We report two outcomes after off-label use of BMPs for the treatment of femur fractures and propose a possible explanation for the difference.

Nonintrusive thermal-wave sensor for operando quantification of degradation in commercial batteries.

Monitoring real-world battery degradation is crucial for the widespread application of batteries in different scenarios. However, acquiring quantitative degradation information in operating commercial cells is challenging due to the complex, embedded, and/or qualitative nature of most existing sensing techniques. This process is essentially limited by the type of signals used for detection.

Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells.

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy.

Extreme fast charging of commercial Li-ion batteries via combined thermal switching and self-heating approaches.

The mass adoption of electric vehicles is hindered by the inadequate extreme fast charging (XFC) performance (i.e., less than 15 min charging time to reach 80% state of charge) of commercial high-specific-energy (i.

Unraveling Li growth kinetics in solid electrolytes due to electron beam charging.

Revealing the local structure of solid electrolytes (SEs) with electron microscopy is critical for the fundamental understanding of the performance of solid-state batteries (SSBs). However, the intrinsic structural information in the SSB can be misleading if the sample's interactions with the electron beams are not fully understood. In this work, we systematically investigate the effect of electron beams on Al-doped lithium lanthanum zirconium oxide (LLZO) under different imaging conditions.

HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.

CCT251236 , a potent chemical probe, was previously developed from a cell-based phenotypic high-throughput screen (HTS) to discover inhibitors of transcription mediated by HSF1, a transcription factor that supports malignancy. Owing to its activity against models of refractory human ovarian cancer, was progressed into lead optimization. The reduction of P-glycoprotein efflux became a focus of early compound optimization; central ring halogen substitution was demonstrated by matched molecular pair analysis to be an effective strategy to mitigate this liability.

Using Thermal Interface Resistance for Noninvasive Operando Mapping of Buried Interfacial Lithium Morphology in Solid-State Batteries.

The lithium metal-solid-state electrolyte interface plays a critical role in the performance of solid-state batteries. However, operando characterization of the buried interface morphology in solid-state cells is particularly difficult because of the lack of direct optical access. Destructive techniques that require isolating the interface inadvertently modify the interface and cannot be used for operando monitoring.

Discovery of a Potent and Orally Bioavailable Zwitterionic Series of Selective Estrogen Receptor Degrader-Antagonists.

Herein, we report the optimization of a meta-substituted series of selective estrogen receptor degrader (SERD) antagonists for the treatment of ER+ breast cancer. Structure-based design together with the use of modeling and NMR to favor the bioactive conformation led to a highly potent series of basic SERDs with promising physicochemical properties. Issues with hERG activity resulted in a strategy of zwitterion formation and ultimately in the identification of .

Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes.

Objective: To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality.

Design: Retrospective cohort study from 2016 to 2020.

Surgically Treated Femoral Neck Stress Fractures Are Likely to Result in Military Separation During Basic Combat Training.

Background: Femoral neck stress fractures are a common condition affecting military service members, most noticeably during basic combat training. Previous studies have investigated the risk factors for femoral neck stress fracture development in basic trainees and outcomes associated with treatment; however, few studies have focused on operatively treated femoral neck stress fracture in the military trainee. Doing so would be important not only for the military, but also providers caring for athletes, such as distance runners, who have a heightened risk for femoral neck stress fracture development.

Is There a Critical Radiographic Angle That Portends Poor Functional Outcome Scores in Nonoperative Treatment of Isolated Humeral Shaft Fractures?

Our purpose was to evaluate radiographic alignment of nonoperatively treated humerus fractures and determine if there is a critical angle associated with worse outcomes. All patients with humeral shaft fractures that were prospectively followed as part of a larger multicenter trial were reviewed. These patients were selected for nonoperative management based on shared decision making.

Operative vs. Nonoperative Treatment of Isolated Humeral Shaft Fractures: A Prospective Cohort Study.

The purpose was to compare plate and screw fixation (open reduction internal fixation [ORIF]) and functional bracing (FB) of isolated humeral shaft fractures with treatment and patient-based outcomes. We performed a prospective trial of ORIF v. FB at 12 centers.

In vitro fertilization and andrology laboratory in 2030: expert visions.

The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of in vitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory.

In vitro fertilization and andrology laboratories in 2030.

The in vitro fertilization and andrology laboratories are at the center of assisted reproductive technologies and the place where technicians and embryologists manipulate gametes and preimplantation-stage embryos with the goal of achieving the best embryo for transfer. Through the years, these laboratories have seen developments in technique, technology, and testing. The goal of this Views and Interviews series is to bring together the thought leaders in the field and envision what the laboratories will look like in the next 10 years.

Addition of Fluorine and a Late-Stage Functionalization (LSF) of the Oral SERD AZD9833.

Herein we describe our efforts using a late stage functionalization together with more traditional synthetic approaches to generate fluorinated analogues of the clinical candidate AZD9833. The effects of the addition of fluorine on the lipophilicity, permeability, and metabolism are discussed. Many of these changes were tolerated in terms of pharmacology and resulted in high quality molecules which reached advanced stages of profiling in the testing cascade.

Donor oocyte recipients do not benefit from preimplantation genetic testing for aneuploidy to improve pregnancy outcomes.

Study Question: Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)?

Summary Answer: PGT-A did not improve the likelihood of live birth for recipients of vitrified donor oocytes, but it did avoid embryo transfer in cycles with no euploid embryos.

What Is Known Already: Relative to slow freeze, oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosome during meiosis II and ultimately increased aneuploidy in resultant embryos.

Gunshot Wounds to the Hip: Doomed to Failure?

The purpose is to evaluate hip fractures due to gunshot wounds (GSW) to the hip, which are treated surgically, and the complications. Patients who sustained a low velocity GSW with fracture to the femoral head/neck and intertrochanteric/peritrochantric region at three Level 1 Trauma Centers were eligible. There were 69 patients (63 males-91%), with an average age of 29 (18-60).

Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.

Herein we report the optimization of a series of tricyclic indazoles as selective estrogen receptor degraders (SERD) and antagonists for the treatment of ER breast cancer. Structure based design together with systematic investigation of each region of the molecular architecture led to the identification of -[1-(3-fluoropropyl)azetidin-3-yl]-6-[(6,8)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3-pyrazolo[4,3-]isoquinolin-6-yl]pyridin-3-amine (). This compound was demonstrated to be a highly potent SERD that showed a pharmacological profile comparable to fulvestrant in its ability to degrade ERα in both MCF-7 and CAMA-1 cell lines.