NIR-Activated Hydrogel with Dual-Enhanced Antibiotic Effectiveness for Thorough Elimination of Antibiotic-Resistant Bacteria.

Antibiotic resistance has become a critical health crisis globally. Traditional strategies using antibiotics can lead to drug-resistance, while inorganic antimicrobial agents can cause severe systemic toxicity. Here, we have developed a dual-antibiotic hydrogel delivery system (PDA-Ag@Levo/CMCS), which can achieve controlled release of clinical antibiotics levofloxacin (Levo) and classic nanoscale antibiotic silver nanoparticles (AgNPs), effectively eliminating drug-resistant .

The causal relationship between gut microbiota and preterm birth: a two-sample Mendelian randomization study.

Background: Preterm birth, a significant global health concern, has been associated with alterations in the gut microbiota. However, the causal nature of this relationship remains uncertain due to the limitations inherent in observational studies.

Purpose: To investigate the potential causal relationship between gut microbiota imbalances and preterm birth.

Molecular insights into the activation mechanism of GPR156 in maintaining auditory function.

The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-G complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus.

The Application of Machine Learning Algorithms to Bond Strength between Steel Rebars and Concrete Using Bayesian Optimization.

The purpose of this study is to estimate the bond strength between steel rebars and concrete using machine learning (ML) algorithms with Bayesian optimization (BO). It is important to conduct beam tests to determine the bond strength since it is affected by stress fields. A machine learning approach for bond strength based on 401 beam tests with six impact factors is presented in this paper.

Assessing Visual Pathway White Matter Degeneration in Primary Open-Angle Glaucoma Using Multiple MRI Morphology and Diffusion Metrics.

Background: Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness, is associated with neurodegeneration in the visual pathway, but the underlying pathophysiology remains incompletely resolved.

Purpose: To characterize macro- and microstructural white matter abnormalities in optic tract (OT) and optic radiation (OR) of POAG.

Study Type: Prospective.

The mechanism of action and chemical synthesis of FDA newly approved drug molecules.

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs.

The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application.

Spatiotemporal pattern and obstacle factors of coupling relationship between habitat quality and urbanization level in the Yellow River Basin, China.

Land use change stands as the primary factor influencing habitat quality (HQ). Clarifying the spatiotemporal change and the obstacle factors of the coupling relationship between HQ and urbanization level (UL) can provide imperative references for achieving sustainability in the Yellow River Basin (YRB). This study is based on the InVEST model, spatial autocorrelation, and obstacle factor analysis to measure the spatiotemporal dynamics and impediments of the coupling relationship between HQ and UL from 2000 to 2020 in the YRB.

Decoding CLU (Clusterin): Conquering cancer treatment resistance and immunological barriers.

One major obstacle in the treatment of cancer is the presence of proteins resistant to cancer therapy, which can impede the effectiveness of traditional approaches such as radiation and chemotherapy. This resistance can lead to disease progression and cause treatment failure. Extensive research is currently focused on studying these proteins to create tailored treatments that can circumvent resistance mechanisms.

Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs.

G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors HR and HR couple with G- or G-proteins respectively.

Identification of Bromophenols' glucuronidation and its induction on UDP- glucuronosyltransferases isoforms.

Bromophenols (BPs) are prominent environmental pollutants extensively utilized in aquaculture, pharmaceuticals, and chemical manufacturing. This study aims to identify UDP- glucuronosyltransferases (UGTs) isoforms involved in the metabolic elimination of BPs. Mono-glucuronides of BPs were detected in human liver microsomes (HLMs) incubated with the co-factor uridine-diphosphate glucuronic acid (UDPGA).

Prevention of Periprosthetic Infection After Orthopedic Knee Replacement Based on 5E Rehabilitation Nursing Model.

Context: Periprosthetic joint infections (PJIs) are a rare but highly destructive complication after total knee arthroplasty (TKA). Nursing plays an important role in preventing postoperative infections in patients, but different nursing modes have different rates of postoperative infections.

Objective: The study intended to explore the effects of "encouragement, education, exercise, employment, and evaluation" (5E) rehabilitation nursing on the prevention of periprosthetic joint infections (PJIs) after TKA.

Structure-based design of non-hypertrophic apelin receptor modulator.

Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through the β-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-G complexes bound to three agonists with divergent signaling profiles.

KIF2C: An important factor involved in signaling pathways, immune infiltration, and DNA damage repair in tumorigenesis.

Backgrounds: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation.

Conformational transitions and activation of the adhesion receptor CD97.

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges.

Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism.

Cannabis activates the cannabinoid receptor 1 (CB1), which elicits analgesic and emotion regulation benefits, along with adverse effects, via G and β-arrestin signaling pathways. However, the lack of understanding of the mechanism of β-arrestin-1 (βarr1) coupling and signaling bias has hindered drug development targeting CB1. Here, we present the high-resolution cryo-electron microscopy structure of CB1-βarr1 complex bound to the synthetic cannabinoid MDMB-Fubinaca (FUB), revealing notable differences in the transducer pocket and ligand-binding site compared with the G protein complex.

Orthosteric and allosteric modulation of human HCAR2 signaling complex.

Hydroxycarboxylic acids are crucial metabolic intermediates involved in various physiological and pathological processes, some of which are recognized by specific hydroxycarboxylic acid receptors (HCARs). HCAR2 is one such receptor, activated by endogenous β-hydroxybutyrate (3-HB) and butyrate, and is the target for Niacin. Interest in HCAR2 has been driven by its potential as a therapeutic target in cardiovascular and neuroinflammatory diseases.

High-fat diet promotes tumor growth in the patient-derived orthotopic xenograft (PDOX) mouse model of ER positive endometrial cancer.

Endometrial cancer, one of the common gynecological malignancies, is affected by several influencing factors. This study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model for the study of influencing factors in ER positive endometrial cancer. The aim of this study was to demonstrate that a high-fat diet can affect the growth of ER positive endometrial cancer PDOX model tumors.

The dynamic patterns and driving factors of land use conflict in the Yellow River basin of China.

Land use conflict, as the spatial manifestation of conflicting human-land relationship, has a profound impact on sustainable use of regional land resources. Taking the Yellow River Basin (YRB) as an example, a land use conflict assessment model was constructed based on landscape pattern indices. The dynamic patterns and driving factors of land use conflict in the YRB and the corresponding driving factors were then assessed from 2000 to 2020 based on spatial autocorrelation analysis and the geodetector method.

Micafungin: A promising inhibitor of UBE2M in cancer cell growth suppression.

Neddylation is a protein modification process similar to ubiquitination, carried out through a series of activating (E1), conjugating (E2), and ligating (E3) enzymes. This process has been found to be overactive in various cancers, leading to increased oncogenic activities. Ubiquitin-conjugating enzyme 2 M (UBE2M) is one of two neddylation enzymes that play a vital role in this pathway.

LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.

Dysregulation of various cells in the tumor microenvironment (TME) causes immunosuppressive functions and aggressive tumor growth. In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. Lysine-specific demethylase 1 (LSD1) is a protein that modifies histone and non-histone proteins and is known to influence a wide variety of physiological processes.