Kidney Targeting Smart Antibiotic Discovery: Multimechanism Pleuromutilins for Pyelonephritis Therapy.

Multidrug-resistant (MDR) bacteria pose a global health threat, underscoring the need for new antibiotics. Lefamulin, the first novel-mechanism antibiotic approved by the FDA in decades, showcases pleuromutilins' promise due to low mutation frequency. However, their clinical use is limited by poor pharmacokinetics and organ toxicity.

Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.

Background: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.

Methods: Rats with MASLD were randomly assigned to undergo DJB or sham surgery.

Improving Hair Scar Defects Through the Integration of Autologous Fat Transplantation and Hair Follicle Unit Transplantation.

Objective: To assess the clinical efficacy of combining autologous fat grafting with hair follicle unit transplantation.

Methods: The authors conducted a retrospective analysis involving 30 patients at the Department of Plastic Surgery, Second Affiliated Hospital of Nanchang University, between January 2021 and January 2023. Granular fat was harvested from the thigh's posterior aspect using liposuction.

Association between circulating inflammatory proteins and temporomandibular disorders: insight from a two-sample Mendelian randomization analysis.

Background: Past studies have indicated links between specific inflammatory proteins in the bloodstream and temporomandibular disorders (TMDs). Nonetheless, there remains the need for further solid research pinpointing the exact causes behind these associations. This Mendelian randomization (MR) study aims to examine the association between 91 circulating inflammatory proteins and TMDs.

Three-dimensional measurement of the depth of invasion in oral squamous cell carcinoma samples using Lugol's iodine-enhanced micro-computed tomography: an original study.

Objectives: Depth of invasion (DOI) in oral squamous cell carcinoma (OSCC) guides treatment and prognosis but lacks three-dimensional (3D) insight. Thus, this study aimed to investigate the feasibility and accuracy of Lugol's iodine-enhanced micro-computed tomography (CT) for the 3D measurement of DOI in OSCC samples.

Methodology: In total, 50 in vitro OSCC samples from Nanjing Stomatological Hospital (July 2022 to January 2024) were subjected to micro-CT imaging with a slice thickness of 50 μm following 3% Lugol iodine staining for 12 h, followed by pathological examination and staining.

ThCTi@(6)-C: Th═C Double Bond in a Mixed Actinide-Transition Metal Cluster.

A thorium-carbon double bond that corresponds to the sum of theoretical covalent double bond radii has long been sought after in the study of actinide-ligand multiple bonding as a synthetic target. However, the stabilization of this chemical bond remains a great challenge to date, in part because of a relatively poor energetic matching between 5f-/6d- orbitals of thorium and the 2s-/2p- frontier orbitals of carbon. Herein, we report the successful synthesis of a thorium-carbon double bond in a carbon-bridged actinide-transition metal cluster, i.

The TRP Channels Serving as Chemical-to-Electrical Signal Converter.

Biology uses many signaling mechanisms. Among them, calcium and membrane potential are two prominent mediators for cellular signaling. TRPM4 and TRPM5, two calcium-activated monovalent cation-conducting ion channels, offer a direct linkage between these two signals.

Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library.

Tuberculosis (TB), caused by the bacterium (), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived fungal library were screened for anti- activity, and an strain with strong anti- activity was found. Three known flavones, chlorflavonin (), dechlorflavonin (), and bromoflavone (), were isolated from this fungus.

Asymmetric Amplification in Oxypalladation/Malononitrile Addition Cascade Enabled by Heterochiral-Assembly of Products.

An enantioselective oxypalladation/malononitrile addition cascade reaction of alkyne-tethered malononitriles was reported to synthesize enaminones bearing an all-carbon quaternary center. Using Pd(TFA)/Pyox as a precatalyst, an array of enaminone products were obtained in moderate overall yields, with excellent er (93.5:6.

Comparison the Cosmetic Outcome of the Triangular Flap Insertion Versus Direct Linear Resection in Correction of Dog Ear Deformities on the Face-A Prospective and Randomized Controlled Trial.

Background: Compared with direct linear resection, the triangular flap insertion method is a correction method that purportedly reduces the incision tension of dog ears deformity. Randomized clinical trials comparing these 2 methods seem to be limited or absent.

Objective: A randomized study was planned to compare the cosmetic effect and scar in the defect area between the triangular flap insertion method and direct linear resection in the repair of dog ear deformities after the suture of the facial circular defect.

Three-dimensional Finite Element Analysis of Implant Prosthesis After Mandibular Reconstruction by Upper Distal Free Double-Barrel Fibula.

Objective: This study aimed to compare the biomechanics of implant prostheses and peri-implant bone among 6 different mandibular reconstruction models based on patient data involving the use of an upper free-end double-barrel fibula.

Methods: This study was an observational study. Five models were reconstructed using fibular-supported and implant-supported partial dentures.

A Multifunctional Synergistic Solar-Driven Interfacial Evaporator for Desalination and Photocatalytic Degradation.

The scarcity of freshwater resources and the treatment of dye wastewater have emerged as unavoidable challenges that need to be addressed. The combination of solar-driven interfacial evaporation, photocatalytic degradation, and superhydrophobic surface provides an effective approach for seawater desalination and the treatment of organic dyes. In this study, we fabricated a multifunctional synergistic solar evaporator by depositing cupric oxide nanoparticles onto polypyrrole (PPy) coating and subsequently modified it with a hydrophobic agent successfully.

Separation of Three Polar Compounds with Similar Polarities from Swertia mussotii by a Combination of Two Counter-Current Chromatography Modes.

Separation of polar compounds especially with similar polarities is challenging. In the present study, three polar compounds with similar polarities, including gentiopicroside, sweroside and mangiferin, have been successfully separated from Swertia mussotii by a combination of two counter-current chromatography modes. With the selected solvent system of ethyl acetate/n-butanol/water (8/2/10, v/v), a continuous injection mode was firstly employed.

Revealing the Active Components and Therapeutic Targets of Sanao Decoction against Chronic Obstructive Pulmonary Disease Using Quantitative Analysis of Multi-Components by Single Marker and Network Pharmacology.

As a traditional Chinese medicine, Sanao decoction (SAD) has been used to treat chronic obstructive pulmonary disease (COPD) for multi-years. However, the potential mechanism and targets for its effects of SAD remain unknown. The 94 components of SAD were identified by UPLC-LTQ-Orbitrap MS.

Dimensional engineering of interlayer for efficient large-area perovskite solar cells with high stability under ISOS-L-3 aging test.

The utilization of low-dimensional perovskites (LDPs) as interlayers on three-dimensional (3D) perovskites has been regarded as an efficient strategy to enhance the performance of perovskite solar cells. Yet, the formation mechanism of LDPs and their impacts on the device performance remain elusive. Herein, we use dimensional engineering to facilitate the controllable growth of 1D and 2D structures on 3D perovskites.

Amphiphilic hemicyanine molecular probes crossing the blood-brain barrier for intracranial optical imaging of glioblastoma.

Intracranial optical imaging of glioblastoma (GBM) is challenging due to the scarcity of effective probes with blood-brain barrier (BBB) permeability and sufficient imaging depth. Herein, we describe a rational strategy for designing optical probes crossing the BBB based on an electron donor-π-acceptor system to adjust the lipid/water partition coefficient and molecular weight of probes. The amphiphilic hemicyanine dye (namely, IVTPO), which exhibits remarkable optical properties and effective BBB permeability, is chosen as an efficient fluorescence/photoacoustic probe for in vivo real-time imaging of orthotopic GBM with high resolution through the intact skull.

Siderophore synthetase-receptor gene coevolution reveals habitat- and pathogen-specific bacterial iron interaction networks.

Bacterial social interactions play crucial roles in various ecological, medical, and biotechnological contexts. However, predicting these interactions from genome sequences is notoriously difficult. Here, we developed bioinformatic tools to predict whether secreted iron-scavenging siderophores stimulate or inhibit the growth of community members.

Insights on the evolution and adaptation toward high-altitude and cold environments in the snow leopard lineage.

How snow leopard gradually adapted to the extreme environments in Tibet remains unexplored due to the scanty fossil record in Tibet. Here, we recognize five valid outside-Tibet records of the snow leopard lineage. Our results suggest that the snow leopard dispersed out of the Tibetan Plateau multiple times during the Quaternary.

Development of a recombinant Ang1 variant with enhanced Tie2 binding and its application to attenuate sepsis in mice.

The angiopoietin (Ang)-Tie axis, critical for endothelial cell function and vascular development, is a promising therapeutic target for treating vascular disorders and inflammatory conditions like sepsis. This study aimed to enhance the binding affinity of recombinant Ang1 variants to the Tie2 and explore their therapeutic potential. Structural insights from the Ang1-Tie2 complex enabled the identification of key residues within the Ang1 receptor binding domain (RBD) critical for Tie2 interaction.

Engineered extracellular vesicles with DR5 agonistic scFvs simultaneously target tumor and immunosuppressive stromal cells.

Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells.

Soft nanoforest of metal single atoms for free diffusion catalysis.

Metal single atoms are of increasing importance in catalytic reactions. However, the mass diffusion is yet substantially limited by the confined surface of the support in comparison to homogeneous catalysis. Here, we demonstrate that cylindrical micellar brushes with highly solvated poly(2-vinylpyridine) coronas can immobilize 33 types of metal single atoms with 8.

A nanoparticle-based wireless deep brain stimulation system that reverses Parkinson's disease.

Deep brain stimulation technology enables the neural modulation with precise spatial control but requires permanent implantation of conduits. Here, we describe a photothermal wireless deep brain stimulation nanosystem capable of eliminating α-synuclein aggregates and restoring degenerated dopamine neurons in the substantia nigra to treat Parkinson's disease. This nanosystem (ATB NPs) consists of gold nanoshell, an antibody against the heat-sensitive transient receptor potential vanilloid family member 1 (TRPV1), and β-synuclein (β-syn) peptides with a near infrared-responsive linker.

Molybdate uptake interplay with ROS tolerance modulates bacterial pathogenesis.

The rare metal element molybdenum functions as a cofactor in molybdoenzymes that are essential to life in almost all living things. Molybdate can be captured by the periplasmic substrate-binding protein ModA of ModABC transport system in bacteria. We demonstrate that ModA plays crucial roles in growth, multiple metabolic pathways, and ROS tolerance in .

Core-Shell Nanoparticles with Sequential Drug Release Depleting Cholesterol for Reverse Tumor Multidrug Resistance.

Multidrug resistance (MDR) facilitates tumor recurrence and metastasis, which has become a main cause of chemotherapy failure in clinical. However, the current therapeutic effects against MDR remain unsatisfactory, mainly hampered by the rigid structure of drug-resistant cell membranes and the uncontrolled drug release. In this study, based on a sequential drug release strategy, we engineered a core-shell nanoparticle (DOX-M@CaP@ATV@HA) depleting cholesterol for reverse tumor MDR.

Macrophage-specific in vivo RNA editing promotes phagocytosis and antitumor immunity in mice.

Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.