Associations between inflammatory burden index, prostate cancer, and mortality among middle-aged and elderly individuals.

Background: Inflammation plays a crucial role in prostate cancer (PCa) progression and mortality. This study aimed to investigate the predictive value of the inflammatory burden index (IBI) and its components for mortality risk among men aged 40 years and older.

Methods: A total of 7,344 participants from the NHANES 2001-2010 were included.

Enhancing Carrier Transport in 2D/3D Perovskite Heterostructures through Organic Cation Fluorination.

The interfacial 2D/3D perovskite heterostructures have attracted extensive attention due to their unique ability to combine the high stability of 2D perovskites with the remarkable efficiency of 3D perovskites. However, the carrier transport mechanism within the 2D/3D perovskite heterostructures remains unclear. In this study, the carrier transport dynamics in 2D/3D perovskite heterostructures through a variety of time-resolved spectroscopic measurements is systematically investigated.

Identification of PANoptosis-related signature reveals immune infiltration characteristics and immunotherapy responses for renal cell carcinoma.

PANoptosis is a specific type of inflammatory programmed cell death (PCD) modality that can be involved in three key modes of cellular programmed cell death-pyroptosis, apoptosis and necroptosis. We analyzed PANoptosis activity in three common renal cell carcinoma subtypes (Clear cell renal cell carcinoma, Papillary renal cell carcinoma, and Chromophobe renal cell carcinoma) separately and constructed a new PANoptosis immunity index (PANII). In three renal cell carcinomas, we found that PANII was an effective predictor of immunotherapy efficacy in KIRC, KIRP and KICH, and the high PANII group was characterized by high immune infiltration and sensitivity to immunotherapy, while the low PANII group was prone to immune escape and immunotherapy resistance.

Bladder Cancer: Immunotherapy and Pelvic Lymph Node Dissection.

Bladder cancer, a common malignancy of the urinary system, is routinely treated with radiation, chemotherapy, and surgical excision. However, these strategies have inherent limitations and may also result in various side effects. Immunotherapy has garnered considerable attention in recent years as a novel therapeutic approach.

Unveiling hormone-stimulated gene mechanisms in prostate cancer: A prognostic model, immune infiltration analysis, and drug sensitivity study.

Hormones promote the progression of prostate cancer (PRCA) through the activation of a complex regulatory network. Inhibition of hormones or modulation of specific network nodes alone is insufficient to suppress the entire oncogenic network. Therefore, it is imperative to elucidate the mechanisms underlying the occurrence and development of PRCA in order to identify reliable diagnostic markers and therapeutic targets.

Directly and ultrasensitivity detecting SARS-CoV-2 spike protein in pharyngeal swab solution by using SERS-based biosensor.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a great disaster to the economy and human society. Nowadays, SARS-CoV-2 is fading away from people's memory but it still exists around us. PCR plays an important role in detecting SARS-CoV-2 but it requires a long detecting time, equipped laboratory, and professional operators.

Elucidation of novel TRAP1-Selective inhibitors that regulate mitochondrial processes.

Hsp90 isoform-selective inhibitors represent a new paradigm for novel anti-cancer drugs as each of the four isoforms have specific cellular localization, function, and client proteins. The mitochondrial isoform, TRAP1, is the least understood member of the Hsp90 family due to the lack of small molecule tools to study its biological function. Herein, we report novel TRAP1-selective inhibitors used to interrogate TRAP1's biological function along with co-crystal structures of such compounds bound to the N-terminus of TRAP1.

Human SAMD9 is a poxvirus-activatable anticodon nuclease inhibiting codon-specific protein synthesis.

As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNA), resulting in codon-specific ribosomal pausing and stress signaling.

Structure-Activity Relationship Study of Tertiary Alcohol Hsp90α-Selective Inhibitors with Novel Binding Mode.

The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of client proteins associated with all 10 hallmarks of cancer. Herein, the design, synthesis, and biological validation of Hsp90α-selective inhibitors that contain a tertiary alcohol are reported. Forty-one analogues were synthesized to modulate hydrogen-bonding interactions and to probe for steric and hydrophobic interactions within the Hsp90α binding site.

Structural basis of the key residue W320 responsible for Hsp90 conformational change.

The 90-kDa heat shock protein (Hsp90) is a homodimeric molecular chaperone with ATPase activity, which has become an intensely studied target for the development of drugs for the treatment of cancer, neurodegenerative and infectious diseases. The equilibrium between Hsp90 dimers and oligomers is important for modulating its function. In the absence of ATP, the passive chaperone activity of Hsp90 dimers and oligomers has been shown to stabilize client proteins as a holdase, which enhances substrate binding and prevents irreversible aggregation and precipitation of the substrate proteins.

EF-hand protein, EfhP, specifically binds Ca and mediates Ca regulation of virulence in a human pathogen Pseudomonas aeruginosa.

Calcium (Ca) is well known as a second messenger in eukaryotes, where Ca signaling controls life-sustaining cellular processes. Although bacteria produce the components required for Ca signaling, little is known about the mechanisms of bacterial Ca signaling. Previously, we have identified a putative Ca-binding protein EfhP (PA4107) with two canonical EF-hand motifs and reported that EfhP mediates Ca regulation of virulence factors production and infectivity in Pseudomonas aeruginosa, a human pathogen causing life-threatening infections.

Crystal structure of the middle and C-terminal domains of Hsp90α labeled with a coumarin derivative reveals a potential allosteric binding site as a drug target.

The 90 kDa heat-shock protein (Hsp90) is an abundant molecular chaperone that is essential to activate, stabilize and regulate the function of a plethora of client proteins. As drug targets for the treatment of cancer and neurodegenerative diseases, Hsp90 inhibitors that bind to the N-terminal ATP-binding site of Hsp90 have shown disappointing efficacy in clinical trials. Thus, allosteric regulation of the function of Hsp90 by compounds that interact with its middle and C-terminal (MC) domains is now being pursued as a mechanism to inhibit the ATPase activity and client protein-binding activity of Hsp90 without concomitant induction of the heat-shock response.

[Corrigendum] SPAG9 expression is increased in human prostate cancer and promotes cell motility, invasion and angiogenesis .

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a pair of data panels presented in each of Figs. 3 and 4 appeared to be overlapping, such that these data may have been derived from the same original sources where they were intended to have shown the results from experiments performed under different experimental conditions. The authors realised that these figures had inadvertently been assembled incorrectly; however, as they had retained their access to the raw data, the authors were able to make the appropriate corrections required for these figures.

Structure and function of an effector domain in antiviral factors and tumor suppressors SAMD9 and SAMD9L.

SAMD9 and SAMD9L (SAMD9/9L) are antiviral factors and tumor suppressors, playing a critical role in innate immune defense against poxviruses and the development of myeloid tumors. SAMD9/9L mutations with a gain-of-function (GoF) in inhibiting cell growth cause multisystem developmental disorders including many pediatric myelodysplastic syndromes. Predicted to be multidomain proteins with an architecture like that of the NOD-like receptors, SAMD9/9L molecular functions and domain structures are largely unknown.

Structure of the unique tetrameric STENOFOLIA homeodomain bound with target promoter DNA.

Homeobox transcription factors are key regulators of morphogenesis and development in both animals and plants. In plants, the WUSCHEL-related homeobox (WOX) family of transcription factors function as central organizers of several developmental programs ranging from embryo patterning to meristematic stem-cell maintenance through transcriptional activation and repression mechanisms. The Medicago truncatula STENOFOLIA (STF) gene is a master regulator of leaf-blade lateral development.

Selective Inhibition of the Hsp90α Isoform.

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone that processes nascent polypeptides into their biologically active conformations. Many of these proteins contribute to the progression of cancer, and consequently, inhibition of the Hsp90 protein folding machinery represents an innovative approach toward cancer chemotherapy. However, clinical trials with Hsp90 N-terminal inhibitors have encountered deleterious side effects and toxicities, which appear to result from the pan-inhibition of all four Hsp90 isoforms.

A semi-dominant NLR allele causes whole-seedling necrosis in wheat.

Programmed cell death (PCD) and apoptosis have key functions in development and disease resistance in diverse organisms; however, the induction of necrosis remains poorly understood. Here, we identified a semi-dominant mutant allele that causes the necrotic death of the entire seedling (DES) of wheat (Triticum aestivum L.) in the absence of any pathogen or external stimulus.

The three-dimensional structure and recognition mechanism of Manduca sexta peptidoglycan recognition protein-1.

Peptidoglycan recognition proteins (PGRPs) recognize bacteria through their unique cell wall constituent, peptidoglycans (PGs). PGRPs are conserved from insects to mammals and all function in antibacterial defense. In the tobacco hornworm Manduca sexta, PGRP1 and microbe binding protein (MBP) interact with PGs and hemolymph protease-14 precursor (proHP14) to yield active HP14.

Structure of a lipid-bound viral membrane assembly protein reveals a modality for enclosing the lipid bilayer.

Cellular membranes are maintained as closed compartments, broken up only transiently during membrane reorganization or lipid transportation. However, open-ended membranes, likely derived from scissions of the endoplasmic reticulum, persist in vaccinia virus-infected cells during the assembly of the viral envelope. A group of viral membrane assembly proteins (VMAPs) were identified as essential for this process.

Structure-guided design of an Hsp90β N-terminal isoform-selective inhibitor.

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 protein folding machinery results in a combinatorial attack on numerous oncogenic pathways. Seventeen small-molecule inhibitors of Hsp90 have entered clinical trials, all of which bind the Hsp90 N-terminus and exhibit pan-inhibitory activity against all four Hsp90 isoforms.

Identification of small molecule inhibitors of Interleukin-18.

Interleukin-18 (IL-18) is a pleiotropic pro-inflammatory cytokine belonging to the IL-1 superfamily. IL-18 plays an important role in host innate and adaptive immune defense but its aberrant activities are also associated with inflammatory diseases such as rheumatoid arthritis and Crohn's disease. IL-18 activity is modulated in vivo by its naturally occurring antagonist, IL-18 Binding Protein (IL-18BP).

Vaccinia Virus A6 Is a Two-Domain Protein Requiring a Cognate N-Terminal Domain for Full Viral Membrane Assembly Activity.

Poxvirus virion biogenesis is a complex, multistep process, starting with the formation of crescent-shaped viral membranes, followed by their enclosure of the viral core to form spherical immature virions. Crescent formation requires a group of proteins that are highly conserved among poxviruses, including A6 and A11 of vaccinia virus (VACV). To gain a better understanding of the molecular function of A6, we established a HeLa cell line that inducibly expressed VACV-A6, which allowed us to construct VACV mutants with an A6 deletion or mutation.

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis.

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data.

Label-Free Real-Time Microarray Imaging of Cancer Protein-Protein Interactions and Their Inhibition by Small Molecules.

A rapid optical microarray imaging approach for anticancer drug screening at specific cancer protein-protein interface targets with binding kinetics and validation by a mass sensor is reported for the first time. Surface plasmon resonance imager (SPRi) demonstrated a 3.5-fold greater specificity for interactions between murine double minute 2 protein (MDM2) and wild-type p53 over a nonspecific p53 mutant in a real-time microfluidic analysis.