Borenium-Catalyzed "Boron Walking" for Remote Site-Selective Hydroboration.

Remote functionalization through progressive olefin isomerization enables site-selective modification at a distal position, diversifying the synthetic approaches. However, the developed protocols have long relied on transition metal catalysis. Transition metal catalysts are deemed irreplaceable, albeit facing challenges in metal residue and catalyst poisoning.

Malaria risk factors amongst forest going populations in Mondulkiri Province and Kampong Speu Province, Cambodia: a large cross-sectional survey.

Background: Cambodia strives to eliminate all species of human malaria by 2025, requiring that foci among forest-exposed populations in remote settings be addressed. This study explores malaria risk factors amongst forest-exposed groups in Mondulkiri and Kampong Speu Provinces, Cambodia as part of a multi-stage study on novel bite prevention tools (Project BITE).

Methods: A serial cross-sectional survey explored the demographics, housing structure openness, mosquito bite prevention habits, and gaps in protection amongst three target groups: forest goers who work in the forest, forest dwellers who live in the forest, and forest rangers who patrol forested regions.

Computer-Aided formulation design for pharmaceutical drug product development, part 01: Materials exploration through a visualization tool.

An interactive tool has been developed to help design oral solid dosage form formulations. The tool enables quantitative explorations and comparisons of physical, bulk, and mechanical properties, and takes into account functional characteristics as well. In this manner, comparisons and clustering of both excipients and APIs can be carried out.

Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models.

Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in App and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness.

Stereodivergent Hydrohalogenation of SCF Alkynes and Cross- Coupling Reactions.

SCF-substituted internal alkynes undergo regio- and stereoselective hydrohalogenation to provide the corresponding β-halo-α-SCF-alkenes. The regioselectivity is ensured by the strong polarization of the C≡C triple bond in SCF-alkynes, while the stereoselectivity is governed by the strength of the proton donor and/or by the solvent polarity. The potential of β-iodo-α-SCF-alkenes was illustrated in several cross-coupling, protodeiodination, and cyanation reactions.

Varying recombination landscapes between individuals are driven by polymorphic transposable elements.

Meiotic recombination is a prominent force shaping genome evolution, and understanding the causes for varying recombination landscapes within and between species has remained a central, though challenging, question. Recombination rates are widely observed to negatively associate with the abundance of transposable elements (TEs), selfish genetic elements that move between genomic locations. While such associations are usually interpreted as recombination influencing the efficacy of selection at removing TEs, accumulating findings suggest that TEs could instead be the cause rather than the consequence.

Immune Checkpoint Inhibitor Therapy for Metastatic Melanoma: What Should We Focus on to Improve the Clinical Outcomes?

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enhancing anti-tumour immune responses, demonstrating significant efficacy in various malignancies, including melanoma. However, over 50% of patients experience limited or no response to ICI therapy. Resistance to ICIs is influenced by a complex interplay of tumour intrinsic and extrinsic factors.

Disparities in hepatitis C among people aged 12-59 with no history of injection drug use, United States, January 2013-March 2020.

Background And Aims: In the United States, hepatitis C virus (HCV) infection occurs primarily through injection drug use (IDU), but transmission also occurs through other ways. This study examined HCV prevalence and disparities among US residents aged 12-59 years with no IDU history.

Methods: We analysed 2013-March 2020 National Health and Nutrition Examination Survey data to calculate the HCV prevalence among people with no drug use history and only a non-IDU history, collectively referred to as no IDU history.

Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies.

Bispecific antibodies (biAbs) used in cancer immunotherapies rely on functional autologous T cells, which are often damaged and depleted in patients with haematological malignancies and in other immunocompromised patients. The adoptive transfer of allogeneic T cells from healthy donors can enhance the efficacy of biAbs, but donor T cells binding to host-cell antigens cause an unwanted alloreactive response. Here we show that allogeneic T cells engineered with a T-cell receptor that does not convert antigen binding into cluster of differentiation 3 (CD3) signalling decouples antigen-mediated T-cell activation from T-cell cytotoxicity while preserving the surface expression of the T-cell-receptor-CD3 signalling complex as well as biAb-mediated CD3 signalling and T-cell activation.

11-Azaartemisinin derivatives bearing halogenated aromatic moieties: Potent anticancer agents with high tumor selectivity.

While artemisinin and its derivatives, including 11-azaartemisinin-based compounds, have shown promising anticancer activity, the integration of halogens into aromatic structures can amplify drug potency, metabolic stability, and selectivity. Herein, we present the synthesis of new novel 11-azaartemisinin derivatives bearing halogenated aromatic moieties connected via 1,2,3-triazole bridges and evaluate their anticancer activities against three human tumor cell lines: epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), and human lung adenocarcinoma (A549). Among the synthesized compounds, six of them (8c-h) displayed good to excellent antiproliferative activity in the low micromolar range across all three human cancer cell lines.

Polycaprolactone Hybrid Scaffold Loaded With N,O-Carboxymethyl Chitosan/Aldehyde Hyaluronic Acid/Hydroxyapatite Hydrogel for Bone Regeneration.

Hydrogels have emerged as potential materials for bone grafting, thanks to their biocompatibility, biodegradation, and flexibility in filling irregular bone defects. In this study, we fabricated a novel NAH hydrogel system, composed of N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronic acid (AHA), and hydroxyapatite (HAp). To improve the mechanical strength of the fabricated hydrogel, a porous polycaprolactone (PCL) matrix was synthesized and used as a three-dimensional (3D) support template for NAH hydrogel loading, forming a novel PCL/NAH hybrid scaffold.

Evolving Characteristics of Decedents With Hepatitis A Listed as a Cause of Death, United States, 2011-2021.

Hepatitis A is a vaccine-preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person-to-person transmission have been widespread in the United States since 2016. We used public-use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A-listed deaths during non-outbreak (2011-2015) and outbreak (2017-2021) periods and assessed the median age at death among decedents with and without hepatitis A-listed deaths during the outbreak period.

IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells.

Background: The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not on normal hematopoietic stem cells (HSCs), providing an opportunity to target and eliminate the disease, while sparing normal hematopoiesis. Herein, we report the activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML.

Methods: Antibodies to IL1RAP were isolated from CD138+ B cells collected from the immunized mice by optoelectric positioning and single cell sequencing.

Upper respiratory tract and orofacial manifestations of new-onset giant cell arteritis: results from a large, prospective inception cohort study.

Objectives: Giant cell arteritis (GCA) often features upper respiratory tract (URT) and orofacial manifestations, which signal the involvement of external carotid artery branches. In this study, we aimed to describe the frequency of various URT/orofacial symptoms at GCA onset, as well as the main characteristics of patients presenting these symptoms.

Methods: We included all patients who were newly diagnosed with GCA between 1976 and April 2022 at the Internal Medicine Department of a tertiary-care hospital.

Simultaneous electrochemical determination of uric acid and hypoxanthine at a TiO/graphene quantum dot-modified electrode.

A TiO/graphene quantum dots composite (TiO/GQDs) obtained by in situ synthesis of GQDs, derived from coffee grounds, and peroxo titanium complexes was used as electrode modifier in the simultaneous electrochemical determination of uric acid and hypoxanthine. The TiO/GQDs material was characterized by photoluminescence, X-ray diffraction, Raman spectroscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray mapping. The TiO/GQDs-GCE exhibits better electrochemical activity for uric acid and hypoxanthine than GQDs/GCE or TiO/GCE in differential pulse voltammetry (DPV) measurements.

Hippo and PI5P4K signaling intersect to control the transcriptional activation of YAP.

Phosphoinositides are essential signaling molecules. The PI5P4K family of phosphoinositide kinases and their substrates and products, PI5P and PI4,5P, respectively, are emerging as intracellular metabolic and stress sensors. We performed an unbiased screen to investigate the signals that these kinases relay and the specific upstream regulators controlling this signaling node.

Oseltamivir (Tamiflu), a Commonly Prescribed Antiviral Drug, Mitigates Hearing Loss in Mice.

Hearing loss affects up to 10% of all people worldwide, but currently there is only one FDA-approved drug for its prevention in a subgroup of cisplatin-treated pediatric patients. Here, we performed an unbiased screen of 1,300 FDA-approved drugs for protection against cisplatin-induced cell death in an inner ear cell line, and identified oseltamivir phosphate (brand name Tamiflu), a common influenza antiviral drug, as a top candidate. Oseltamivir phosphate was found to be otoprotective by oral delivery in multiple established cisplatin and noise exposure mouse models.

Association between maternal depression symptoms and child telomere length.

The biological mechanisms that explain how adverse early life events influence adult disease risk are poorly understood. One proposed mechanism is via the induction of accelerated biological aging, for which telomere length is considered a biomarker. We aimed to determine if maternal depression pre- and post-partum was associated with telomere length in children at 4 years of age (n = 4299).