WNT1-inducible signaling pathway protein 1 activation through C-X-C motif chemokine ligand 5/C-X-C chemokine receptor type 2/leukemia inhibitory factor/leukemia inhibitory factor receptor signaling promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types.

Binding of interleukin-1 receptor antagonist to cholinergic receptor muscarinic 4 promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses.

MCTP1 increases the malignancy of androgen-deprived prostate cancer cells by inducing neuroendocrine differentiation and EMT.

Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms by which ADT induces neuroendocrine differentiation in advanced PCa. We found that transmembrane protein 1 (MCTP1), which has putative Ca sensing function and multiple Ca-binding C2 domains, was abundant in samples from patients with advanced PCa.

Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.

Background: Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates.

Objective: In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs.

Immunosuppressive role of BDNF in therapy-induced neuroendocrine prostate cancer.

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME.

Cu(II) Coordination Polymers Containing Mixed Ligands with Different Flexibilities: Structural Diversity and Iodine Adsorption.

Reactions of '-(3-methylpyridyl)oxalamide (), ,'-(3-methylpyridyl)adipoamide () and ,'-(3-methylpyridyl)sebacoamide () with tricarboxylic acids and Cu(II) salts afforded {[Cu()(1,3,5-HBTC)]·HO} (1,3,5-HBTC = 1,3,5-benzenetricarboxylic acid), , {[Cu()(1,3,5-BTC)(HO)]·6.5HO}, , [Cu()(1,3,5-HBTB)] (1,3,5-HBTB = 1,3,5-tri(4-carboxyphenyl)benzene), , [Cu()(OH)(1,3,5-BTC)], , {[Cu()(1,3,5-BTB)]·2.5MeOH·2HO}, , and {[Cu()(1,3,5-BTB) ]·DMF·2HO}, , which have been structurally characterized by using single crystal X-ray crystallography.

Association of creatinine-albumin ratio with 28-day mortality in major burned patients: A retrospective cohort study.

Background: Serum creatinine (Cr) and Albumin (Alb) have emerged as prognostic factors for mortality in many diseases including burned patients. However, few studies report the relationship between Cr/Alb ratio and major burned patients. The purpose of this study is to make evaluation of efficacy of Cr/Alb ratio in predicting 28-day mortality in major burned patients.

CHRM4/AKT/MYCN upregulates interferon alpha-17 in the tumor microenvironment to promote neuroendocrine differentiation of prostate cancer.

Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer.

Mortality Evaluation and Life Expectancy Prediction of Patients with Hepatocellular Carcinoma with Data Mining.

Background: The complexity of systemic variables and comorbidities makes it difficult to determine the best treatment for patients with hepatocellular carcinoma (HCC). It is impossible to perform a multidimensional evaluation of every patient, but the development of guidelines based on analyses of said complexities would be the next best option. Whereas conventional statistics are often inadequate for developing multivariate predictive models, data mining has proven more capable.

Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine differentiation of castration-resistant prostate cancer.

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However, the metabolic pathways that regulate NE differentiation (NED) in PCa remain unclear.

Th1/Th2 cytokine levels: A potential diagnostic tool for patients with necrotizing fasciitis.

Introduction: Necrotizing fasciitis (NF) has emerged as rare but rapidly progressive, life-threatening severe skin and soft tissue infection. We conducted a study to investigate whether Th1/Th2 cytokines could serve as biomarkers to distinguish NF from class III skin and soft tissue infections (SSTIs).

Methods: A retrospective review was performed for 155 patients suffering from serious skin and soft tissue infections from October 2020 to February 2022.

One new furanone analogue from the deep-sea fungus sp. SCSIO 06693.

A new furanone analog, ()-2-(8,9-dihydroxy-6,8-dimethyldec-4-en-2-yl)-met-hylfuran-3()-one (), together with six known compounds, including two diterpenoids ( and ), one butyrolactone () and three isocoumarins (), were isolated from a deep-sea fungus, sp. SCSIO 06693. Among them, compound existed as two tautomeric forms ( and ) differing in configuration of the furan ring.

Pyruvate kinase L/R links metabolism dysfunction to neuroendocrine differentiation of prostate cancer by ZBTB10 deficiency.

Neuroendocrine differentiation (NED) frequently occurs in androgen-deprivation therapy (ADT)-resistant prostate cancer (PCa) and is typically associated with metabolic pathway alterations, acquisition of lineage plasticity, and malignancy. There is no conventional therapeutic approach for PCa patients with NED pathologic features because the molecular targets are unknown. Here, we evaluated the regulatory mechanism of NED-associated metabolic reprogramming induced by ADT.

PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer.

Background: Castration-resistant prostate cancer (CRPC) patients frequently develop neuroendocrine differentiation, with high mortality and no effective treatment. However, the regulatory mechanism that connects neuroendocrine differentiation and metabolic adaptation in response to therapeutic resistance of prostate cancer remain to be unravelled.

Methods: By unbiased cross-correlation between RNA-sequencing, database signatures, and ChIP analysis, combining in vitro cell lines and in vivo animal models, we identified that PCK1 is a pivotal regulator in therapy-induced neuroendocrine differentiation of prostate cancer through a LIF/ZBTB46-driven glucose metabolism pathway.

TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer.

Neuroendocrine differentiation (NED) is associated with WNT signaling activation and can be significantly observed after failure of androgen-deprivation therapy (ADT) for prostatic adenocarcinomas. Cytokine signaling is stimulated in NED prostate cancer; however, how ADT-upregulated WNT signaling promotes activation of cytokine signaling and contributes to NED of prostate cancer is poorly understood. In this study, we identified ADT-mediated upregulation of transcription factor 7 like 1 (TCF7L1), which increases the cytokine response and enhances NED of prostate cancer through interleukin (IL)-8/C-X-C motif chemokine receptor type 2 (CXCR2) signaling activation.

A glyoxylate-containing benzene derivative and butenolides from a marine algicolous fungus sp. SCSIO 41304.

A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3'-methyl-2'-butenyl)phenyl)-2-oxoacetate (), together with ten known compounds (-), were isolated from the marine algicolous fungus, sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data.

Indole diketopiperazine alkaloids and aromatic polyketides from the Antarctic fungus sp. SCSIO 05705.

A new indole diketopiperazine alkaloid, named penilline D (), together with five known indole alkaloid analogues (-, ), two meroterpenoids ( and ), and four butenolide derivatives (-), were isolated from the Antarctic fungus sp. SCSIO 05705. Extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation were used to elucidate the structure of penilline D (), including its absolute configuration.

Zanubrutinib Treatment of Central Nervous System Posttransplant Lymphoproliferative Disorder After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

Posttransplant lymphoproliferative disorder (PTLD) is a rare complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with poor prognosis. We report a patient with PTLD involved central nervous system (CNS) who treated with zanubrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor. Our report supports the efficacy of bruton tyrosine kinase inhibitor zanubrutinib in the treatment of CNS-PTLD, which provides a new therapeutic option.

Pyrrolyl 4-quinolone alkaloids from the mangrove endophytic fungus Penicillium steckii SCSIO 41025: Chiral resolution, configurational assignment, and enzyme inhibitory activities.

Six undescribed 4-quinolone alkaloids, including four racemic mixtures, (±)-oxypenicinolines A-D, and two related ones, penicinolines F and G, together with seven known analogues, were isolated from the mangrove-derived fungus Penicillium steckii SCSIO 41025 (Trichocomaceae). The racemates were separated by HPLC using chiral columns. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) experiments, and single-crystal X-ray diffraction analysis.

Nerve growth factor interacts with CHRM4 and promotes neuroendocrine differentiation of prostate cancer and castration resistance.

Nerve growth factor (NGF) contributes to the progression of malignancy. However, the functional role and regulatory mechanisms of NGF in the development of neuroendocrine prostate cancer (NEPC) are unclear. Here, we show that an androgen-deprivation therapy (ADT)-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcriptional activation of NGF.

Diketopiperazine and enterotoxin analogues from the mangrove derived-soil sp. SCSIO 41400 and their biological evaluation.

A new diketopiperazine, cyclo-(-8-acetoxyl-Pro--Leu) (), together with eight known compounds (-) including three enterotoxins (-), four diketopiperazines (-) and maltol (), were isolated from the mangrove derived-soil sp. SCSIO 41400. The planar structures of all compounds were determined from analysis of NMR spectra, MS, optical rotation and comparing with literature data.

EGFR-upregulated LIFR promotes SUCLG2-dependent castration resistance and neuroendocrine differentiation of prostate cancer.

Neuroendocrine (NE) differentiation is a well-recognized phenotypic change of prostate cancer after androgen deprivation therapy (ADT), and it ultimately develops into an aggressive subset of this disease. However, the contribution of signaling pathways that lead to metabolic disorders and NE differentiation of prostate cancer remains unclear. In this study, we identified that ADT induced upregulation of the succinate-CoA ligase GDP-forming beta subunit (SUCLG2), which regulates succinate metabolism and NE differentiation of prostate cancer.

Investigation of the - structures and isomerization of oligoprolines by using Raman spectroscopy and density functional theory calculations: solute-solvent interactions and effects of terminal positively charged amino acid residues.

Using low-wavenumber Raman spectroscopy in combination with theoretical calculations solid-state density functional theory (DFT)-D3, we studied the vibrational structures and interaction with solvent of poly-l-proline and the oligoproline P12 series. The P12 series includes P12, the positively charged amino acid residue (arginine and lysine) N-terminus proline oligomers RP11 and KP11, and the C-terminus P11R and P11K. We assigned the spring-type phonon mode to 74-76 cm bands for the PPI and PPII conformers and the carbonyl group ring-opening mode 122 cm in the PPI conformer of poly-l-proline.

Study of Electronic and Vibrational Structures of Reduced, Neutral, and Oxidized Ni(dpa)X Using Density Functional Theory and Raman Spectroscopy.

The electronic and vibrational structures of trinickel metal string complexes [Ni(dpa)X] (X = Cl, NCS) were investigated using both theoretical calculations and spectroscopic methods. We used the density functional theory (DFT) method B3LYP*-D3, including less exact exchange energy and the van der Waals interaction of metal ions, to obtain the geometries and vibrational structures, which were found to be in excellent agreement with the experimental data. The ground state of Ni(dpa)X is an antiferromagnetic (AF) singlet state, and the next state is a quintet state, which was detected using temperature-dependent Raman spectroscopy under a magnetic field.