Prognostic value of pre-treatment [18F] FDG PET/CT in recurrent nasopharyngeal carcinoma without distant metastasis.

BACKGROUND: [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). METHODS: A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). RESULTS: In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). CONCLUSION: The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging.

Four new species of Dothideomycetes (Ascomycota) from Pará Rubber (Heveabrasiliensis) in Yunnan Province, China.

The tropical areas in southern and south-western Yunnan are rich in fungal diversity. Additionally, the diversity of seed flora in Yunnan Province is higher than in other regions in China and the abundant endemic species of woody plants provide favourable substrates for fungi. Rubber plantations in Yunnan Province are distributed over a large area, especially in Xishuangbanna. During a survey of rubber-associated fungi in Yunnan Province, China, dead rubber branches with fungal fruiting bodies were collected. Morphological characteristics and multigene phylogenetic analyses (ITS, LSU, SSU, rpb2 and tef1-α) revealed four distinct new species, described herein as Melomastiapuerensis, Nigrogranalincangensis, Pseudochaetosphaeronemalincangensis and Pseudochaetosphaeronemaxishuangbannaensis. Detailed descriptions, illustrations and phylogenetic trees are provided to show the taxonomic placements of these new species.

Exogenous application of ascorbic acid improves physiological and productive traits of Nigella sativa.

For thousands of years, plants have been utilized for medicinal purposes. For its naturally existing antibacterial properties, Nigella sativa is one of the most researched herbs. A study was conducted during rabi 2020-21 at The University of Haripur in order to evaluate the potential of ascorbic acid as plant growth enhancer. Two concentrations of ascorbic acid i-e 350 µm and 400 µm were sprayed along with control and water only spray on Nigella sativa crop. The study was arranged in RCBD two factor factorial arrangement. Factor A: ascorbic acid concentrations along with control and water spray, factor B: Growth stages (Stage1 = 40 days after sowing, Stage 2 = 80 DAS, Stage 3 = 120 DAS, Stage 4 = 40 + 80 DAS, Stage 5 = 40 + 120 DAS, Stage 6 = 80 + 120 DAS, Stage 7 = 40 + 80 + 120 DAS). Crop was sown in first week of November. Results reviled that chlorophyll b content, fixed oil content, 1000 seed weight, grain yield, Photosynthetic rate (µ mole m-2s-1), Transpiration rate (mmole m-2s-1), photosynthetic water use efficiency, Internal CO2 concentration (Ci) of leaf tissue and Stomatal conductance (mmole m-2s-1) were significantly affected by ascorbic acid concentrations and stage of application. Crop growth rate increased by 19.88% and 17.29%, chlorophyll b by 12.3% and 11.2%, fixed oil by 11.7% and 9%, grain yield by 10.29% and 9.8%, harvest index by 4% and 5.7% photosynthetic rate by 33%, 20% and stomatal conductance by 24.24% and 24.25 with application of ascorbic acid @ 350 µm, over control and water spray respectively. On the basis of these results it is concluded that application of ascorbic acid at the rate of 350 µm, followed by ascorbic acid at the rate of 400 µm significantly improves black cumin (Nigella sativa) yield and production. Hence it is recommended to apply ascorbic acid at the rate of 350 µm at 40 + 80+120 days after sowing of Nigella sativa crop for obtaining maximum results.

Novel CDK19-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake.

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.

Paramphibambusabambusicola gen. et. sp. nov., Arecophilaxishuangbannaensis and A.zhaotongensis spp. nov. in Cainiaceae from Yunnan, China.

Morphological comparisons and multi locus phylogenetic analyses (base on the combined genes of ITS, LSU, rpb2 and tub) demonstrated that three new saprobic taxa isolated from bamboo belong to Cainiaceae. These taxa comprise a novel genus Paramphibambusa (P.bambusicolasp. nov.) and two new species, Arecophilaxishuangbannaensis and A.zhaotongensis. The three new taxa belong to Cainiaceae (Xylariales, Sordariomycetes) a poorly studied family, which now comprises eight genera. Paramphibambusa can be distinguished from other Cainiaceae genera in having ascomata with a neck and ascospores lacking longitudinal striation, germ slits or germ pores. The two new Arecophila species clustered in a clade with Arecophila sp. and A.bambusae. Detailed morphological descriptions, illustrations, and an updated phylogenetic tree are provided for the new taxa.

Evaluation of a novel model incorporating serological indicators into the conventional TNM staging system for nasopharyngeal carcinoma.

BACKGROUND: Non-anatomical factors significantly affect treatment guidance and prognostic prediction in nasopharyngeal carcinoma (NPC) patients. Here, we developed a novel survival model by combining conventional TNM staging and serological indicators. METHODS: We retrospectively enrolled 10,914 eligible patients with nonmetastatic NPC over 2009-2017 and randomly divided them into training (n = 7672) and validation (n = 3242) cohorts. The new staging system was constructed based on T category, N category, and pretreatment serological markers by using recursive partitioning analysis (RPA). RESULTS: In multivariate Cox analysis, pretreatment cell-free Epstein-Barr virus (cfEBV) DNA levels of >2000 copies/mL [HROS (95 % CI) = 1.78 (1.57-2.02)], elevated lactate dehydrogenase (LDH) levels [HROS (95 % CI) = 1.64 (1.41-1.92)], and C-reactive protein-to-albumin ratio (CAR) of >0.04 [HROS (95 % CI) = 1.20 (1.07-1.34)] were associated with negative prognosis (all P < 0.05). Through RPA, we stratified patients into four risk groups: RPA I (n = 3209), RPA II (n = 2063), RPA III (n = 1263), and RPA IV (n = 1137), with 5-year overall survival (OS) rates of 93.2 %, 86.0 %, 80.6 %, and 71.9 % (all P < 0.001), respectively. Compared with the TNM staging system (eighth edition), RPA risk grouping demonstrated higher prognostic prediction efficacy in the training [area under the curve (AUC) = 0.661 vs. 0.631, P < 0.001] and validation (AUC = 0.687 vs. 0.654, P = 0.001) cohorts. Furthermore, our model could distinguish sensitive patients suitable for induction chemotherapy well. CONCLUSION: Our novel RPA staging model outperformed the current TNM staging system in prognostic prediction and clinical decision-making. We recommend incorporating cfEBV DNA, LDH, and CAR into the TNM staging system.

Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms.

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.

Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer.

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/ß-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival.

Uterine microbial communities and their potential role in the regulation of epithelium cell cycle and apoptosis in aged hens.

BACKGROUND: Alterations of the uterine microbiome are closely associated with various intrauterine diseases and physiological conditions, which are well-established in mammals. However, as representative oviparous animals, the research on the uterine microbial ecosystem and its functions with physiological homeostasis is limited in chickens. Additionally, continuous egg-laying disrupts the oviducal immune defenses of aged hens, susceptible to pathogen invasion, causing poor egg quality and food-borne infections in humans. Here, we investigated aging-related changes in the oviduct microbial colonization and transmission from the gut to eggs and their roles in a hen model. RESULTS: The results of 16S rDNA sequencing showed significant differences in the oviduct microbial composition between young (38 weeks) and aged (77 weeks) laying hens. SourceTracker analysis further revealed differences in the effects of microbial transmission on the oviducal microbiota between young and aged hens. Enhanced barrier defense with cell apoptosis suppression and cell cycle arrest of the uterus were observed in aged hens reducing microbial transmission from the lower to upper reproductive tract. In addition, a total of 361 significantly differential metabolites were identified using metabolomics in the aged uterine microbiota, especially in products of amino acid metabolism and biosynthesis of various secondary metabolites, which might have essential effects on cell apoptosis by regulating immune responses and cell cycle. Notably, antibiotics disrupted uterine microbiota by dietary intervention and direct perfusion did not retard aging-related physiological changes but further aggravated aging processes by disrupting the cell cycle and apoptosis. CONCLUSIONS: The microbiota continuum along the reproductive tract in aged birds differs from that in young birds, especially with a significant shift in the uterus. The aged uterine microbiota probably contributes to the regulation of cell cycle and apoptosis by microbial metabolites primarily involved in amino acid metabolism and biosynthesis of various secondary metabolites. These findings provide new insights into the roles of the reproductive tract microbiota in regulating the cell programming of the aged host, contributing to the exploration of the microbiome as a target for diagnosing aging health status and therapy for gynecological diseases in women. Video Abstract.

Connecting the multiple dimensions of global soil fungal diversity.

How the multiple facets of soil fungal diversity vary worldwide remains virtually unknown, hindering the management of this essential species-rich group. By sequencing high-resolution DNA markers in over 4000 topsoil samples from natural and human-altered ecosystems across all continents, we illustrate the distributions and drivers of different levels of taxonomic and phylogenetic diversity of fungi and their ecological groups. We show the impact of precipitation and temperature interactions on local fungal species richness (alpha diversity) across different climates. Our findings reveal how temperature drives fungal compositional turnover (beta diversity) and phylogenetic diversity, linking them with regional species richness (gamma diversity). We integrate fungi into the principles of global biodiversity distribution and present detailed maps for biodiversity conservation and modeling of global ecological processes.

Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor.

BACKGROUND: Pexidartinib (Turalio) is the only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant-cell tumor (TGCT) associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. This study assessed patient-reported treatment experiences and symptom improvement among patients receiving pexidartinib. METHODS: A cross-sectional, web-based survey collected data on demographics, disease history, pexidartinib dosing, and symptoms before and after pexidartinib use. RESULTS: Of 288 patients enrolled in the Turalio REMS program in May 2021, 83 completed the survey: mean age was 44.2 years, 62.7% were female, and most common tumor sites were in knee (61%) and ankle (12%). Mean initial dose was 622 mg/day: 29 patients reported reduction from initial dose and 8 had dose reduction after titrating up to a higher dose. At the time of survey completion, median time on pexidartinib was 6.0 months; 22 (26.5%) patients discontinued pexidartinib due to physician suggestion, abnormal laboratory results, side effect, or symptom improvement. Compared with before pexidartinib initiation, most patients reported improvement in overall TGCT symptom (78.3%) and physical function (77.2%) during pexidartinib treatment. Significant improvement was reported during pexidartinib treatment in worst stiffness numeric rating scale (NRS) (3.0 vs. 6.2, P < .05) and worst pain NRS (2.7 vs. 5.7, P < .05). CONCLUSION: Findings from this cross-sectional survey confirmed the benefit of pexidartinib in improving symptoms and functional outcomes among patients with symptomatic TGCTs from the patients' perspective. Future research is warranted to examine the long-term benefit and risk of pexidartinib.

Predictive value of radiomic signature based on 2-[18F]FDG PET/CT in HER2 status determination for primary breast cancer with equivocal IHC results.

PURPOSE: To evaluate the predictive power of 2-[18F]FDG PET/CT-derived radiomic signature in human epidermal growth factor receptor 2 (HER2) status determination for primary breast cancer (BC) with equivocal immunohistochemistry (IHC) results for HER2. METHODS: A total of 154 primary BC with equivocal IHC results for HER2 were retrospectively enrolled in the study. First, the following five conventional PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were measured and compared between HER2-positive and HER2-negative cohorts. After quantitative radiomic features extraction and reduction, the least absolute shrinkage and selection operator (LASSO) algorithm was used to establish a radiomic signature model. Then, the area under the curve (AUCs) after a receiver operator characteristic (ROC) analysis, accuracy, sensitivity and specificity were calculated and used as the main outcomes. Finally, a total of 37 BC patients from an external institution were included to perform an external validation. RESULTS: All the five conventional PET parameters were unable to discriminate between HER2-positive and HER2-negative cohorts for BC (P = 0.104-0.544). Whereas, the developed radiomic signature model was potentially predictive of HER2 status with an of AUC 0.887 (95% confidence interval [CI], 0.824-0.950) in the training cohort and 0.766 (95% CI, 0.616-0.916) in the validation cohort, respectively. For external validation, the AUC for the external test cohort was 0.788 (95% CI, 0.633-0.944). CONCLUSIONS: Radiomic signature based on 2-[18F]FDG PET/CT images was capable of non-invasively predicting the HER2 status with a comparable ability to FISH assay, especially for those with equivocal IHC results for HER2.

Transition Mechanism from the Metastable Two-Dimensional Gel to the Stable Three-Dimensional Crystal of Imidazolium-Based Ionic Liquids.

One important quest for making high quality materials with amphiphiles is to understand how a disordered self-assembly changes to a stable crystalline state. Herein, we addressed the basic question by investigating the phase transition mechanism of imidazolium-based ionic liquid (IL) [C16mim]Br, using time-resolved small- and wide-angle X-ray scattering (SAXS-WAXS), differential scanning calorimetry, and Fourier transform infrared spectroscopy techniques. Totally, a hexagonal phase, two lamellar-gel phases, and three lamellar-crystalline phases were observed, showing the special polymorphism of the system. It was demonstrated that at low concentrations the two-dimensional gel phase (Lß1) transforms into the most stable lamellar-crystal phase (Lc3) through two intermediate crystalline phases Lc1 and Lc2. At high concentrations, the Lß1 phase changes to a condensed lamellar gel phase (Lß2) before changing to Lc2 and eventually to Lc3. Comparative studies using [C16mim]Cl and [C16mim]NO3 unveiled that the interactions between the counterions and the headgroups of the IL, as well as the dehydration process, govern the nucleation process of Lc3 and thus the formation of the crystal. The in-depth investigation on the transition mechanism and the phase polymorphism in the present work advances our understanding of the crystallization of amphiphilic ionic liquids in dispersions and would promote future applications.

Role of N6-methyladenosine RNA modification in gastric cancer.

N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification of mammalian messenger RNA. The m6A modification affects multiple aspects of RNA metabolism, including processing, splicing, export, stability, and translation through the reversible regulation of methyltransferases (Writers), demethylases (Erasers), and recognition binding proteins (Readers). Accumulating evidence indicates that altered m6A levels are associated with a variety of human cancers. Recently, dysregulation of m6A methylation was shown to be involved in the occurrence and development of gastric cancer (GC) through various pathways. Thus, elucidating the relationship between m6A and the pathogenesis of GC has important clinical implications for the diagnosis, treatment, and prognosis of GC patients. In this review, we evaluate the potential role and clinical significance of m6A-related proteins which function in GC in an m6A-dependent manner. We discuss current issues regarding m6A-targeted inhibition of GC, explore new methods for GC diagnosis and prognosis, consider new targets for GC treatment, and provide a reasonable outlook for the future of GC research.

Development and characterization of self-emulsifying high internal phase emulsions using endogenous phospholipids from Antarctic krill oil.

High internal phase emulsions (HIPEs) have emerged as a promising structured oil system in food industry. This study developed self-emulsifying HIPEs (SHIPEs) using Antarctic krill oil (KO) with endogenous phospholipids as surfactant and algae oil as a diluent. The influence of phospholipids self-assembly on SHIPEs formation was investigated by evaluating the microstructures, particle size, rheological properties, and water distribution. Results demonstrated that the concentration and self-assembly behavior of phospholipids dominated the SHIPEs formation. Optimized SHIPEs with desirable gel properties contained 10 wt% krill oil in the oil phase at an 80 wt% oil phase level. Furthermore, these SHIPEs exhibited excellent performance in 3D printing applications. Hydrated phospholipids formed lamellar network at the oil-water interface, enhancing gel strength by crosslinking oil droplets. These findings shed light on the self-assembly of phospholipids during HIPEs formation and highlight the potential phospholipids-rich marine lipids in SHIPEs for functional food products development.

PET imaging of new target CDK19 in prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) is a superior method to predict patients' risk of cancer progression and response to specific therapies. However, its performance is limited for neuroendocrine prostate cancer (NEPC) and PSMA-low prostate cancer cells, resulting in diagnostic blind spots. Hence, identifying novel specific targets is our aim for diagnosing those prostate cancers with low PSMA expression. METHODS: The Cancer Genome Atlas (TCGA) database and our cohorts from men with biopsy-proven high-risk metastatic prostate cancer were used to identify CDK19 and PSMA expression. PDX lines neP-09 and P-16 primary cells were used for cellular uptake and imaging mass cytometry in vitro. To evaluate in vivo CDK19-specific uptake of gallium(Ga)-68-IRM-015-DOTA, xenograft mice models and blocking assays were used. PET/CT imaging data were obtained to estimate the absorbed dose in organs. RESULTS: Our study group had reported the overexpression of a novel tissue-specific gene CDK19 in high-risk metastatic prostate cancer and CDK19 expression correlated with metastatic status and tumor staging, independently with PSMA and PSA levels. Following up on this new candidate for use in diagnostics, small molecules targeting CDK19 labeled with Ga-68 (68Ga-IRM-015-DOTA) were used for PET in this study. We found that the 68Ga-IRM-015-DOTA was specificity for prostate cancer cells, but the other cancer cells also took up little 68Ga-IRM-015-DOTA. Importantly, mouse imaging data showed that the NEPC and CRPC xenografts exhibited similar signal strength with 68Ga-IRM-015-DOTA, but 68Ga-PSMA-11 only stained the CRPC xenografts. Furthermore, target specificity was elucidated by a blocking experiment on a CDK19-bearing tumor xenograft. These data concluded that 68Ga-CDK19 PET/CT was an effective technology to detect lesions with or without PSMA in vitro, in vivo, and in the PDX model. CONCLUSION: Thus, we have generated a novel PET small molecule with predictive value for prostate cancer. The findings indicate that 68Ga-CDK19 may merit further evaluation as a predictive biomarker for PET scans in prospective cohorts and may facilitate the identification of molecular types of prostate cancer independent of PSMA.