Reverse

RESEARCH QUESTION: Does the observed correlation between dyslipidaemia and endometriosis indicate a bidirectional causal association? DESIGN: Bidirectional Mendelian randomization was used to investigate the causal association between lipid traits and endometriosis. Drug-target Mendelian randomization was used to explore potential drug-target genes for managing endometriosis. In cases where lipid-mediated effects via specific drug targets were significant, aggregate analyses, such as summary-data-based Mendelian randomization and colocalization methods, were introduced to validate the outcomes...

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear...

In fission yeast lacking the telomere binding protein, Taz1, replication forks stall at telomeres, triggering deleterious downstream events. Strand invasion from one taz1Δ telomeric stalled fork to another on a separate (non-sister) chromosome leads to telomere entanglements, which are resolved in mitosis at 32°C; however, entanglement resolution fails at ≤20°C, leading to cold-specific lethality. Previously, we found that loss of the mitotic function of Rif1, a conserved DNA replication and repair factor, suppresses cold sensitivity by promoting resolution of entanglements without affecting entanglement formation...

OBJECTIVES: Naloxone is an effective medication used to reverse opioid overdoses. Distributing naloxone directly to those at risk, therefore, reduces the risk of opioid-related deaths. New legislation in Australia means a prescription is no longer required to access naloxone. Whilst acknowledging the benefits of increased access, we aim to evaluate the impact psychiatrists can have on naloxone provision due to their unique position as doctors often working with those who may be at risk...

Molecular strain can be introduced to influence the outcome of chemical reactions. Once a thermodynamic product is formed, however, reversing the course of a strain-promoted reaction is challenging. Here, a reversible, strain-promoted polymerization in cyclic DNA is reported. The use of nonhybridizing, single-stranded spacers as short as a single nucleotide in length can promote DNA cyclization. Molecular strain is generated by duplexing the spacers, leading to ring opening and subsequent polymerization. Then, removal of the strain-generating duplexers triggers depolymerization and cyclic dimer recovery via enthalpy-driven cyclization and entropy-mediated ring contraction...

The hydrologic cycle has wide impacts on the ocean salinity and circulation, carbon and nitrogen cycles, and the ecosystem. Under anthropogenic global warming, previous studies showed that the intensification of the hydrologic cycle is a robust feature. Whether this trend persists in hothouse climates, however, is unknown. Here, we show in climate models that mean precipitation first increases with rising surface temperature, but the precipitation trend reverses when the surface is hotter than ~320 to 330 kelvin...

HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during viral replication. However, the viral and host factors that trigger uncoating remain unidentified. Recent studies show that infectious cores enter the nucleus and uncoat near the site of integration. Here, we show that efficient uncoating of nuclear cores requires synthesis of a double-stranded DNA (dsDNA) genome >3.5 kb and that the efficiency of uncoating correlates with genome size. Core disruption by capsid inhibitors releases viral DNA, some of which integrates...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the Activator Protein-1 (AP-1) (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens (Fra-) 1 and 2 is unknown. Here, we show that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun/Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2hep mice...

Small interfering RNA (siRNA) is known for its ability to silence the expression of specific genes, demonstrating its promising potential as a therapeutic approach. Self-assembled micelle inhibitory RNA (SAMiRNA) is an oligonucleotide duplex developed to overcome the in vivo delivery limitations of siRNA. SAMiRNA has hydrophilic and hydrophobic groups at both ends of a sense strand, forming a spherical nanostructure that enhances the in vivo delivery efficiency. Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the most commonly used method for the analysis of oligonucleotides...

The performance of all-solid-state lithium batteries (ASSLBs) is significantly impacted by lithium interfacial instability, which originates from the dynamic chemical, morphological, and mechanical changes during deep Li plating and stripping. In this study, we introduce a facile approach to generate a conductive and regenerative solid interface, enhancing both the Li interfacial stability and overall cell performance. The regenerative interface is primarily composed of nanosized lithium iodide (nano-LiI), which originates in situ from the adopted solid-state electrolyte (SSE)...

Plant cells need to respond to environmental stimuli and developmental signals accurately and promptly. Ubiquitylation is a reversible posttranslational modification that enables the adaptation of cellular proteostasis to internal or external factors. The different topologies of ubiquitin linkages serve as the structural basis for the ubiquitin code, which can be interpreted by ubiquitin-binding proteins or readers in specific processes. The ubiquitylation status of target proteins is regulated by ubiquitylating enzymes or writers, and deubiquitylating enzymes (DUBs) or erasers...

Molecular motors have found a wide range of applications, powering a transition from molecules to dynamic molecular systems for which their motion must be precisely tuned. To achieve this adjustment, strategies involving laborious changes in their design are often used. Herein, we show that control over a single methyl group allows a drastic change in rotational properties. In this regard, we present the straightforward asymmetric synthesis of β-methylated first-generation overcrowded-alkene-based molecular motors...

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis...

During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video-tracking system. Intercellular Ca2+ dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2- and parvalbumin-GCaMP6 mice, respectively...

The beneficial effects of probiotics, postbiotics, and paraprobiotics have already been registered in managing ischemic stroke-generated neuroinflammation and gut dysbiosis. Herein, we examined the impact of cell-free supernatant (CFS) obtained from probiotics (Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01) in a rat transient middle cerebral artery occlusion (MCAO) model of focal cerebral injury. Pre-MCAO supplementation of probiotics (2 × 109  CFU/mL) for 21 days or CFS (1 mL/rat) for 7 days protect the MCAO-induced somatosensory and motor impairments recorded at 24 h and 72 h after reperfusion in foot-fault, rotarod, adhesive removal, and vibrissae-evoked forelimb placing tests...

This paper revisits Fleeming Jenkin's anonymous review of Charles Darwin's Origin of Species, published in the North British Review in June 1867. This review is usually revered for its impact on Darwin's theory of descent with modification. Its classical interpretation states that Jenkin, a Professor of Engineering at the University of Edinburgh, made a compelling case against natural selection based on the fact of "blending inheritance" and the "swamping" of advantageous variations. Those themes, however, are strikingly absent from Jenkin's text...

PURPOSE: The aim of the present systematic review is to collect all the available evidence regarding the clinical and radiological results of revision to reverse shoulder arthroplasty (RSA) of modular anatomic shoulder prostheses (TSA) using a convertible metal-backed glenoid (MBG). METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies investigating revision of TSA to RSA utilizing a convertible MBG and reporting clinical and radiological outcomes were identified...

IMPORTANCE: Evaluating the impact of statewide contraceptive access initiatives is necessary for informing health policy and practice. OBJECTIVE: To examine changes in contraceptive method use among a cohort of women of reproductive age in South Carolina during the Choose Well contraceptive access initiative. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, baseline data from the initial Statewide Survey of Women administered from October 1, 2017, to April 30, 2018, to a probability-based sample of women of reproductive age in South Carolina and a peer state (Alabama) were linked with 3 follow-up surveys given in 2019, 2020, and 2021...

Geomagnetic field (GMF) protects living organisms on the Earth from the radiation coming from space along with other environmental factors during evolution, and it has affected the growth and development of plants. Many researchers have always been interested in investigating these effects in different aspects. In this chapter, we focus on the methods of using different types of magnetic fields (MFs) to investigate the dimensions of their biological effects on plants. The aim is to increase seed germination, growth characters, and yield of plants using the following methods: (1) Using MFs lower than GMF to study effects of GMF on the growth and yield of plants...

Derivatization of monosaccharides with 1-phenyl-3-methyl-5-pyrazolone (PMP) introduces two chromophores per sugar molecule. Their separation on a superficially porous C18 reverse-phase column, using common liquid chromatography equipment, results in short analysis times (under 20 min) and high sensitivity (limit of quantitation 1 nmol). This method allows for complex monosaccharide mixtures to be separated and quantified using a reasonably simple and safe derivatization procedure.