Discovery of novel seven-membered ring derivatives of ONC212 as caseinolytic protease P protein activators using the ring expansion strategy: Rational design, synthesis, and antibacterial evaluation.

Caseinolytic protease P (ClpP) protein is essential for prokaryotic and eukaryotic protein homeostasis, and has emerged as a promising bactericidal target for controlling bacterial infection and evading the emergent of drug-resistance risk. As the unique bactericidal mechanism, ClpP loses its substrate specificity and undergoes uncontrolled protein hydrolysis in the presence of an activator, leading to causing bacterial death. To further expand the chemotype of ClpP activator, a series of ONC212 derivatives were synthesized using a ring expansion strategy.

Enhanced mucosal immune response through nanoparticle delivery system based on chitosan-catechol and a recombinant antigen targeted towards M cells.

In mucosal vaccination, the targeted delivery of antigens through M (microfold) cells is essential for initiating a robust antigen-specific immune response. In the present study, we devised a nano-delivery platform to target M cells. This platform involved coating mesoporous silica nanoparticles (MSN) with a mucoadhesive chitosan-catechol (Chic) layer, incorporating a recombinant antigen to form nanoparticles that enhance the immune response.

FOXF2 expression triggered by endocrine therapy orchestrates therapeutic resistance through reorganization of chromatin architecture in breast cancer.

Patients with estrogen receptor-positive (ER+) breast cancer require long-term endocrine therapy. However, endocrine resistance remains a critical issue to be addressed. Herein, we show that ERα repressed FOXF2 transcription in ER+ breast cancer through facilitating H3K27me3 deposition around its genomic locus, therefore endocrine therapy triggered FOXF2 transcription via loss of H3K27me3.

Modulation in Spin State of CoO Decorated Fe Single Atom Enables a Superior Rechargeable Zinc-Air Battery Performance.

High-performance bifunctional electrocatalyst for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is the keystone for the industrialization of rechargeable zinc-air battery (ZAB). In this work, the modulation in the spin state of Fe single atom on nitrogen doped carbon (Fe-NC) is devised by CoO (CoO@Fe-NC), and a mediate spin state is recorded. Besides, the d band center of Fe is downshifted associated with the increment in e filling revealing the weakened interaction with OH moiety, resulting in a boosted ORR performance.

Toll-Like Receptor 4 (TLR4) Promotes DRG Regeneration and Repair after Sciatic Nerve Injury via the ERK-NF-kB Pathway.

Previously, we found that the expression of Toll-like receptor 4 (TLR4) is altered after sciatic nerve injury, and its differential expression plays a key role in recovery. However, the mechanisms by which TLR4 affects neuronal function in the dorsal root ganglion (DRG) have not been completely evaluated. The objective is to determine TLR4 expression in DRG tissues after sciatic neural injury and exploring the effects of TLR4 knockdown and overexpression in the DRG on neuronal function and nerve regeneration in rats in vivo and in vitro.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1-benzo[]imidazole () exhibited optimal antifungal activity against (), affording an excellent half-maximal effective concentration (EC) of 0.

Dual immunotherapy alternating with anti-PD-1 antibody plus liposomal doxorubicin show good efficacy in prostate epithelioid hemangioendothelioma: a case report.

Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date.

Engineering a biomimicking strategy for discovering nonivamide-based quorum-sensing inhibitors for controlling bacterial infection.

The overuse of antibiotics over an extended period has led to increasing antibiotic resistance in pathogenic bacteria, culminating in what is now considered a global health crisis. To tackle the escalating disaster caused by multidrug-resistant pathogens, the development of new bactericides with new action mechanism is highly necessary. In this study, using a biomimicking strategy, a series of new nonivamide derivatives that feature an isopropanolamine moiety [the structurally similar to the diffusible signal factor (DSF) of Xanthomonas spp.

Pathogen-Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization.

Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan-catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions.

Preoperative fasting glucose value can predict acute kidney injury in non-cardiac surgical patients without diabetes but not in patients with diabetes.

Background: Postoperative acute kidney injury (AKI) is a common and costly complication after non-cardiac surgery. Patients with or without diabetes could develop hyperglycemia before surgery, and preoperative hyperglycemia was closely associated with postoperative poor outcomes, but the association between preoperative fasting blood glucose level and postoperative AKI is still unclear.

Methods: Data from patients undergoing non-cardiac surgery in Chongqing University Cancer Hospital from January 1, 2017, to May 31, 2023, were collected, preoperative glucose value and perioperative variables were extracted, the primary exposure of interest was preoperative glucose value, and the outcome was postoperative AKI.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy.

Purpose: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs).

Methods: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group.

Beyond the β-amino alcohols framework: identification of novel β-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

Background: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases.

Multifunctional Sr/Se co-doped ZIF-8 nanozyme for chemo/chemodynamic synergistic tumor therapy apoptosis and ferroptosis.

Cancer continues to be a significant public health issue. Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues such as lack of specificity and poor drug delivery, leading to insufficient drug concentration at the tumor site and/or potential side effects. Consequently, improving the delivery of conventional chemotherapy drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy.

Isolation of endophytes from Dioscorea nipponica Makino for stimulating diosgenin production and plant growth.

Both bacterial and fungal endophytes exhibited one or more plant growth-promoting (PGP) traits. Among these strains, the Paenibacillus peoriae SYbr421 strain demonstrated the greatest activity in the direct biotransformation of tuber powder from D. nipponica into diosgenin.

Association Between Intraoperative Noradrenaline Infusion and Outcomes in Older Adult Patients Undergoing Major Non-Cardiac Surgeries: A Retrospective Propensity Score-Matched Cohort Study.

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes.

Complete mitochondrial genome of the endangered (Prunoideae, Rosaceae) in China: characterization and phylogenetic analysis.

Introduction: (Prunoideae: Rosaceae), a relic shrub with strong resistance and multiple application values, is endangered in China. Extensive research had been devoted to gene expression, molecular markers, plastid genome analysis, and genetic background investigations of . However, the mitochondrial genome of this species has not been systematically described, owing to the complexity of the plant mitogenome.