Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Molecular H as the Reducing Agent in Low-Temperature Oxide Reduction Using Calcium Hydride.

Low-temperature synthesis is crucial for advancing sustainable manufacturing and accessing novel metastable phases. Metal hydrides have shown great potential in facilitating the reduction of oxides at low temperatures, yet the underlying mechanism─whether driven by H, H, or atomic H─remains unclear. In this study, we employ electrical transport measurements and first-principles calculations to investigate the CaH-driven reduction kinetics in epitaxial α-FeO thin films.

Controlled Synthesis of Perovskite Nanocrystals at Room Temperature by Liquid Crystalline Templates.

Perovskite nanocrystals (PNCs) are promising active materials because of their outstanding optoelectronic properties, which are finely tunable via size and shape. However, previous synthetic methods such as hot-injection and ligand-assisted reprecipitation require a high synthesis temperature or provide limited access to homogeneous PNCs, leading to the present lack of commercial value and real-world applications of PNCs. Here, we report a room-temperature approach to synthesize PNCs within a liquid crystalline antisolvent, enabling access to PNCs with a precisely defined size and shape and with reduced surface defects.

A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.

Medium-Sized Rotator Cuff Tears Repaired With Transosseous-Equivalent Technique Plus Bone Marrow Stimulation Yielded Similar Short-Term Outcomes Regardless of Whether Complete or Incomplete Footprint Coverage Was Achieved.

Purpose: To compare clinical outcomes and retear rates of medium-sized rotator cuff tears repaired with incomplete footprint coverage using the transosseous-equivalent technique versus those with complete footprint coverage plus bone marrow stimulation.

Methods: The retrospective study, conducted from March 2019 to December 2021, included consecutive patients with medium-sized (1-3 cm) posterosuperior rotator cuff tears repaired using the transosseous-equivalent technique and bone marrow stimulation, with a minimum follow-up of 2 years. Patients were divided into 2 groups based on the degree of footprint coverage achieved: group C (complete coverage) and group I (incomplete coverage).

Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.

Background: Osteoarthritis (OA) is a painful degenerative joint disease and a leading source of years lived with disability globally due to inadequate treatment options. Neuroimmune interactions reportedly contribute to OA pain pathogenesis. Notably, in rodents, macrophages in the DRG are associated with onset of persistent OA pain.

Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis.

Approach to the Diagnosis and Management of Complex Fascicular Ventricular Tachycardias.

Complex ventricular tachycardias involving the fascicular system (fascicular ventricular tachycardias [FVTs]) can be challenging. In this review, we describe our approach to the diagnosis and ablation of these arrhythmias with 10 illustrative cases that involve (1) differentiation from supraventricular tachycardia; (2) assessment for atypical bundle branch reentry and other interfascicular FVTs; (3) examination of P1/P2 activation sequences in sinus rhythm, pacing, and tachycardia; and (4) entrainment techniques to establish the tachycardia mechanism and aid circuit localization. To summarize, 5 cases had prior ablation with 2 previously misdiagnosed as supraventricular tachycardia.

Lipid nanoparticle-mediated mRNA delivery to CD34 cells in rhesus monkeys.

Transplantation of ex vivo engineered hematopoietic stem cells (HSCs) can lead to robust clinical responses but carries risks of adverse events from bone marrow mobilization, chemotherapy conditioning and other factors. HSCs have been modified in vivo using lipid nanoparticles (LNPs) decorated with targeting moieties, which increases manufacturing complexity. Here we screen 105 LNPs without targeting ligands for effective homing to the bone marrow in mouse.

Long-Term Outcome of Rescue Stenting for Acute Intracranial Atherosclerotic Stenosis Related Large Vessel Occlusion in Anterior Circulation.

Background And Purpose: Rescue stent (RS) is an accepted rescue option after failed mechanical thrombectomy (MT) for acute ischemic stroke due to intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion (LVO). However, the long-term outcomes (≥ 12 months) of RS have not yet been elucidated.

Materials And Methods: We retrospectively analyzed the data of 154 patients with RS for ICAS-related LVO, which were identified from prospectively maintained multicenter database of RS after MT failure, to assess good outcome (mRS 0-2), mortality, stroke recurrence, symptomatic intracranial hemorrhage (SICH) and stent patency.

A multilineage screen identifies actionable synthetic lethal interactions in human cancers.

Cancers are driven by alterations in diverse genes, creating dependencies that can be therapeutically targeted. However, many genetic dependencies have proven inconsistent across tumors. Here we describe SCHEMATIC, a strategy to identify a core network of highly penetrant, actionable genetic interactions.

Deep learning-based algorithm for automatic quantification of nigrosome-1 and Parkinsonism classification using susceptibility map-weighted MRI.

Background And Purpose: To develop and validate a deep learning-based automatic quantification for nigral hyperintensity and a classification algorithm for neurodegenerative parkinsonism using susceptibility map-weighted imaging (SMwI).

Materials And Methods: We retrospectively collected 450 participants (210 with idiopathic Parkinson's disease [IPD] and 240 individuals in the control group) for training data between November 2022 and May 2023, and 237 participants (168 with IPD, 58 with essential tremor, and 11 with drug-induced Parkinsonism) for validation data between July 2021 and January 2022. SMwI data were reconstructed from multi-echo GRE.

Saturation profiling of drug-resistant genetic variants using prime editing.

Methods to characterize the functional effects of genetic variants of uncertain significance (VUSs) have been limited by incomplete coverage of the mutational space. In clinical oncology, drug resistance arising from VUSs can prevent optimal treatment. Here we introduce PEER-seq, a high-throughput method based on prime editing that can evaluate the functional effects of single-nucleotide variants (SNVs).

The "Hedgehog-Halo Sign" Is Associated with Gait Symptom Severity and Tap Response in Normal Pressure Hydrocephalus.

Background: Reduced cerebrospinal fluid (CSF) clearance may play a vital role in the pathogenesis of normal pressure hydrocephalus (NPH), but the radiologic marker is yet to be elucidated.

Objectives: This open-label study presents two novel neuroimaging biomarkers based on enlarged perivascular spaces (ePVS) of the sub-insular territory: the Hedgehog and Hedgehog-Halo (H-H) sign, designed to predict gait symptom severity and tap response in NPH.

Methods: We retrospectively reviewed 203 patients with possible NPH with baseline magnetic resonance imaging and gait analyses before and after lumbar puncture (LP).

Clinical profile of patients with acute traumatic brain injury undergoing cranial surgery in the United States: report from the 18-centre TRACK-TBI cohort study.

Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery.

Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014-2018; ClinicalTrials.

Global Comparison of COVID-19 Vaccination Rates among Psoriasis Patients.

(1) Background: The purpose of this study is to compare the rate of COVID-19 vaccination among psoriasis patients internationally and to correlate it with their treatment regimens. (2) Methods: We conducted a cross-sectional study from January 2021 to October 2022 among adults in the United States (US), Chile, China, Switzerland, and Singapore using the Global Healthcare Study on Psoriasis survey. (3) Results: A total of 310 psoriasis patients in the US (98), Chile (32), China (80), Switzerland (39), and Singapore (61) were surveyed.

Evaluation of a Cosmetic Formulation Containing Arginine Glutamate in Patients with Burn Scars: A Pilot Study.

Patients with burn scars require effective treatments able to alleviate dry skin and persistent itching. Ion pairing has been employed in cosmetic formulations to enhance solubility in solvents and improve skin permeability. To evaluate the efficacy and safety of the cosmetic formula "RE:pair (arginine-glutamate ion pair)", we analyzed scar size, itching and pain, skin barrier function, scar scale evaluation, and satisfaction in our study participants.

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences.

Can a Continuous Wound Infiltration System Replace Intravenous Patient-Controlled Analgesia for Postoperative Pain Management after a Single-Port Access Laparoscopy?

The aim of this study was to determine whether continuous wound infiltration (CWI) can replace intravenous patient-controlled analgesia (IV PCA) and to investigate effective pain control strategies after a single-port access (SPA) laparoscopy for adnexal disease. : A total of 470 patients (the CWI group [n = 109], the IV PCA group [n = 198], and the combined group [n = 163]) who underwent an SPA adnexal laparoscopy and who received CWI or IV PCA for postoperative pain management were retrospectively reviewed. The numeric rating scale (NRS) pain score at 6, 12, 24, and 48 h (h) after surgery and the total amount of fentanyl administered via IV PCA were collected.