Decomposition of exotic versus native aquatic plant litter in a lake littoral zone: Stoichiometry and life form analyses.

The decomposition rates and stoichiometric characteristics of many aquatic plants remain unclear, and our understanding of material flow and nutrient cycles within freshwater ecosystems is limited. In this study, an in-situ experiment involving 23 aquatic plants (16 native and 7 exotic species) was carried out via the litter bag method for 63 days, during which time the mass loss and nutrient content (carbon (C), nitrogen (N), and phosphorus (P)) of plants were measured. Floating-leaved plants exhibited the highest decomposition rate (0.038 ± 0.002 day-1), followed by submerged plants and free-floating plants (0.029 ± 0.002 day-1), and emergent plants had the lowest decomposition rate (0.019 ± 0.001 day-1). Mass loss by aquatic plants correlated with stoichiometric characteristics; the decomposition rate increased with an increasing P content and with a decreasing C content, C:N ratio, and C:P ratio. Notably, the decomposition rate of submerged exotic plants (0.044 ± 0.002 day-1) significantly exceeded that of native plants (0.026 ± 0.004 day-1), while the decomposition rate of emergent exotic plants was 55 ± 4 % higher than that of native plants. The decomposition rates of floating-leaved and free-floating plants did not significantly differ between the native and exotic species. During decomposition, emergent plants displayed an increase in C content and a decrease in N content, contrary to patterns observed in other life forms. The P content decreased for submerged (128 ± 7 %), emergent (90 ± 5 %), floating-leaved (104 ± 6 %), and free-floating plants (32 ± 6 %). Exotic plants released more C and P but accumulated more N than did native plants. In conclusion, the decomposition of aquatic plants is closely linked to litter quality and influences nutrient cycling in freshwater ecosystems. Given these findings, the invasion of the littoral zone by submerged and emergent exotic plants deserves further attention.

The role of microRNAs in axon regeneration after peripheral nerve injury: a bibliometric analysis.

Objective: This study analyzed the current research hotspots and future development trends of the therapeutic effects of microRNA on PNI axonal regeneration through bibliometric methods. Moreover, the current advantages and disadvantages of this field as well as future development prospects are discussed in depth. Methods: CiteSpace V and VOSviewer were used as bibliometric tools to complete the analysis of the research focus and direction of the published articles. To supplement, sort out, and summarize, we analyzed the research status of the study on the application of microRNAs for axonal regeneration after peripheral nerve injury from 2013 to 2023. Results: A total of 207 publications were retrieved from the Web of Science database. After exclusion and screening, a final selection of 174 articles that met the research criteria. These 174 articles were authored by a total of 846 individuals, representing 24 countries and 199 institutions. Additionally, this study presents information on the annual publication output, country distribution, top 5 contributing authors, top 5 most cited articles, and top 10 contributing institutions. Conclusion: As one of the hottest topics today, microRNAs have become the current research hotspot in neural inflammation, neural cell repair and regeneration, neural protection, and functional recovery. With more investment in research in this field, more high-quality articles will be published in both domestic and international outstanding journals, which will bring a new era for the treatment of peripheral nerve injury.

Species-specific functional trait responses of canopy-forming and rosette-forming macrophytes to nitrogen loading: Implications for water-sediment interactions.

Globally intensified lake eutrophication, attributed to excessive anthropogenic nitrogen loading, emerges as a significant driver of submerged vegetation degradation. Consequently, the impact of nitrogen on the decline of submerged macrophytes has received increasing attention. However, a functional trait-based approach to exploring the response of submerged macrophytes to nitrogen loading and its environmental feedback mechanism was unclear. Our study utilized two different growth forms of submerged macrophytes (canopy-forming Myriophyllum spicatum, and rosette-forming Vallisneria natans) to established "submerged macrophytes-water-sediment" microcosms. We assessed the influence of nitrogen loading, across four targeted total nitrogen concentrations (original control, 2, 5, 10 mg/L), on plant traits, water parameters, sediment properties, enzyme activities, and microbial characteristics. Our findings revealed that high nitrogen (10 mg/L) adversely impacted the relative growth rate of fresh biomass and total chlorophyll content in canopy-forming M. spicatum, while the chlorophyll a/b and free amino acid content increased. On the contrary, the growth and photosynthetic traits of resource-conservative V. natans were not affected by nitrogen loading. Functional traits (growth, photosynthetic, and stoichiometric) of M. spicatum but not V. natans exhibited significant correlations with environmental variables. Nitrogen loading significantly increased the concentration of nitrogen components in overlying water and pore water. The presence of submerged macrophytes significantly reduced the ammonia nitrogen and total nitrogen both in overlying water and pore water, and decreased total organic carbon in pore water. Nitrogen loading significantly inhibited sediment extracellular enzyme activities, but the planting of submerged macrophytes mitigated their negative effects. Furthermore, rhizosphere bacterial interactions were less compact compared to bare control, while eukaryotic communities exhibited increased complexity and connectivity. Path modeling indicated that submerged macrophytes mitigated the direct effects of nitrogen loading on overlying water and amplified the indirect effects on pore water, while also attenuating the direct negative effects of pore water on extracellular enzymes. The findings indicated that the restoration of submerged vegetation can mitigate eutrophication resulting from increased nitrogen loading through species-specific changes in functional traits and direct or indirect feedback mechanisms in the water-sediment system.

Predation risk-mediated indirect effects promote submerged plant growth: Implications for lake restoration.

Biological manipulation, involving fish stockings, is commonly used to counteract the deterioration of submerged vegetation in eutrophic lakes. Nevertheless, the non-consumptive effects (NCEs) of stocked carnivorous fish are often overlooked. Using a controlled experimental system, we investigated the NCEs of a native carnivorous fish, snakehead (Channa argus), on two key biological factors, herbivore-dominated grass carp (Ctenopharyngodon idella) and disturbance-dominated loach (Misgurnus anguillicaudatus), influencing submerged plants growth. Additionally, we conducted a meta-analysis on predation risk and primary productivity. The results reveal that predation risk induces oxidative stress damage and affects grass carp growth. Non-significant changes in cortisol and glucose may be linked to predation risk prediction. Simultaneously, predation risk reduces fish feeding and disturbance behavior, relieving pressure on submerged plants to be grazed and disturbed, thereby supporting plant development. The presence of submerged plants, in turn, enhances loach activity and influences water body characteristics through negative feedback. Furthermore, the meta-analysis results indicate the facilitative effect of predation risk on primary producers. Our findings contribute to the understanding of biological manipulation theory. We demonstrate that the predation risk associated with introducing carnivorous fish can promote the growth of submerged plants through behaviorally mediated indirect effects. This highlights the potential utility of predation risk in lake restoration efforts.

Mechanistic insight into the impact of polystyrene microparticle on submerged plant during asexual propagules germination to seedling: Internalization in functional organs and alterations of physiological phenotypes.

Asexual reproduction is one of the most important propagations in aquatic plants. However, there is a lack of information about the growth-limiting mechanisms induced by microplastics on the submerged plant during asexual propagule germination to seedling. Hence, we investigated the effects of two sizes (2 µm, 0.2 µm) and three concentrations (0.5 mg/L, 5 mg/L, and 50 mg/L) of polystyrene microplastics (PSMPs) on Potamogeton crispus turion germination and seedling growth. Both PSMPs sizes were found in P. crispus seedling tissues. Metabolic profile alterations were observed in leaves, particularly affecting secondary metabolic pathways and ATP-binding cassette transporters. Metal elements are indispensable cofactors for photosynthesis; however, alterations in the metabolic profile led to varying degrees of reduced concentrations in magnesium, iron, copper, and zinc within P. crispus. Therefore, the maximum quantum yield of photosystem II significantly decreased in all concentrations with 0.2 µm-PSMPs, and at 50 mg/L with 2 µm-PSMPs. These findings reveal that internalization of microplastics, nutrient absorption inhibition, and metabolic changes contribute to the negative impact on P. crispus seedlings.

Integration of metabolomics and transcriptomics to reveal the mechanism of Gerberae piloselloidis herba in alleviating bronchial asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Gerberae Piloselloides Herba (GPH) is derived from Gerbera piloselloides (Linn.) Cass. It is a commonly used traditional medicine in China, featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial and anti-tumor. It is often used as an effective treatment for cough and sore throat as well as bronchial asthma (BA) in China. It was demonstrated in our previous studies that GPH exerted significant effects on the treatment of BA, but its underlying mechanism remains unclear. AIM OF THE STUDY: This study was aimed at revealing the mechanism through which GPH protects against BA. MATERIALS AND METHODS: The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking. RESULTS: GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking. CONCLUSION: GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.

Four new glycosides isolated from Gerbera delavayi Franch.

Phytochemical investigation of the whole plant of Gerbera delavayi afforded four new glycosides including three coumarin glycosides, Gerbelavinside A (1), Gerbelavinside B (2) and Gerbelavinside C (3) and one acetophenone glycoside, Gerbelavinside F (4). The structures of isolated compounds were elucidated by analysis of 1D and 2D NMR, HR-ESI-MS, acid hydrolysis, as well as comparing with the literature. The isolated compounds were examined the effects of nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and Gerbelavinside C presented a certain inhibitory activity.

Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke.

The present study elucidated cuproptosis-related molecular clusters involved in ischemic stroke and developed predictive models. Transcriptomic and immunological profiles of ischemic stroke-related datasets were extracted from the Gene Expression Omnibus database. Next, we conducted weighted gene co-expression network analysis to determine cluster-specific differentially expressed genes (DEGs). Models such as random forest and eXtreme gradient boosting (XGB) were evaluated to select the best prediction performance model. Subsequently, we validated the model's predictive efficiency by using nomograms, decision curve analysis, calibration curves, and receiver operating characteristic curve analysis with an external dataset. We identified two cuproptosis-related clusters involved in ischemic stroke. The DEGs in Cluster 2 were closely associated with amino acid metabolism, various immune responses, and cell proliferation pathways. The XGB model showed lower residuals, a smaller root mean square error, and a greater area under the curve value (AUC = 0.923), thus exhibiting the best discriminative performance. The AUC value for the external validation dataset was 0.921, thus confirming the high performance of the model. NFE2L2, NLRP3, GLS, LIPT1, and MTF1 were identified as potential cuproptosis predictors, thus shedding new light on ischemic stroke pathogenesis and heterogeneity.

Analysis of compatibility mechanism of shenxiong glucose injection after multiple dosing based on differences of PK-PD correlation and cytochrome P450 enzyme.

Shenxiong glucose injection (SGI) containing a water extract from the roots of Danshen and Ligustrazine hydrochloride, is the main drug used for the prevention and treatment of acute myocardial ischemia (AMI) in China. Based on the characteristics of drug clinical applications, this study aims to uncover the compatibility mechanism of SGI by investigating pharmacokinetic (PK) and pharmacodynamic (PD) differences between Danshen glucose injection (DGI), Ligustrazine glucose injection (LGI) and SGI groups after multiple dosing during the pathological state from the perspective of metabolic enzymes. Compared to the LGI group, the absorption (Cmax) and exposure (AUC) of ligustrazine increased significantly, and the protein expression of CYP1A2, CYP2C11 and CYP3A2 in the SGI group decreased significantly. Furthermore, the PK and PD experimental data for Danshen and ligustrazine in AMI rats were fitted to obtain a PK-PD binding model with three components. PK-PD parameter analysis showed that in the SGI group the IC50 values of ligustrazine and danshensu on AST, CK-MB, cTn-I and the IC50 values of rosmarinic acid on AST and CK-MB were lower than the DGI or LGI group. It is speculated that Danshen inhibited CYP1A2, CYP2C11 and CYP3A2 mediating the metabolism of ligustrazine and decreased the expression of these three isozymes, which further affected the in vivo process of ligustrazine. Moreover, the combination of Danshen and ligustrazine could have better regulating effect on AST, CK-MB and cTn-I. This preliminary study has provided a scientific basis for understanding the compatibility mechanism of SGI from the viewpoint of the regulation of CYP enzymes in the PK-PD model.

Deep learning for classifying the stages of periodontitis on dental images: a systematic review and meta-analysis.

BACKGROUND: The development of deep learning (DL) algorithms for use in dentistry is an emerging trend. Periodontitis is one of the most prevalent oral diseases, which has a notable impact on the life quality of patients. Therefore, it is crucial to classify periodontitis accurately and efficiently. This systematic review aimed to identify the application of DL for the classification of periodontitis and assess the accuracy of this approach. METHODS: A literature search up to November 2023 was implemented through EMBASE, PubMed, Web of Science, Scopus, and Google Scholar databases. Inclusion and exclusion criteria were used to screen eligible studies, and the quality of the studies was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. Random-effects inverse-variance model was used to perform the meta-analysis of a diagnostic test, with which pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated, and a summary receiver operating characteristic (SROC) plot was constructed. RESULTS: Thirteen studies were included in the meta-analysis. After excluding an outlier, the pooled sensitivity, specificity, positive LR, negative LR and DOR were 0.88 (95%CI 0.82-0.92), 0.82 (95%CI 0.72-0.89), 4.9 (95%CI 3.2-7.5), 0.15 (95%CI 0.10-0.22) and 33 (95%CI 19-59), respectively. The area under the SROC was 0.92 (95%CI 0.89-0.94). CONCLUSIONS: The accuracy of DL-based classification of periodontitis is high, and this approach could be employed in the future to reduce the workload of dental professionals and enhance the consistency of classification.

The Discovery of Indole-2-carboxylic Acid Derivatives as Novel HIV-1 Integrase Strand Transfer Inhibitors.

As an important antiviral target, HIV-1 integrase plays a key role in the viral life cycle, and five integrase strand transfer inhibitors (INSTIs) have been approved for the treatment of HIV-1 infections so far. However, similar to other clinically used antiviral drugs, resistance-causing mutations have appeared, which have impaired the efficacy of INSTIs. In the current study, to identify novel integrase inhibitors, a set of molecular docking-based virtual screenings were performed, and indole-2-carboxylic acid was developed as a potent INSTI scaffold. Indole-2-carboxylic acid derivative 3 was proved to effectively inhibit the strand transfer of HIV-1 integrase, and binding conformation analysis showed that the indole core and C2 carboxyl group obviously chelated the two Mg2+ ions within the active site of integrase. Further structural optimizations on compound 3 provided the derivative 20a, which markedly increased the integrase inhibitory effect, with an IC50 value of 0.13 µM. Binding mode analysis revealed that the introduction of a long branch on C3 of the indole core improved the interaction with the hydrophobic cavity near the active site of integrase, indicating that indole-2-carboxylic acid is a promising scaffold for the development of integrase inhibitors.

Feasibility and effectiveness of automatic deep learning network and radiomics models for differentiating tumor stroma ratio in pancreatic ductal adenocarcinoma.

OBJECTIVE: This study aims to compare the feasibility and effectiveness of automatic deep learning network and radiomics models in differentiating low tumor stroma ratio (TSR) from high TSR in pancreatic ductal adenocarcinoma (PDAC). METHODS: A retrospective analysis was conducted on a total of 207 PDAC patients from three centers (training cohort: n = 160; test cohort: n = 47). TSR was assessed on hematoxylin and eosin-stained specimens by experienced pathologists and divided as low TSR and high TSR. Deep learning and radiomics models were developed including ShuffulNetV2, Xception, MobileNetV3, ResNet18, support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and logistic regression (LR). Additionally, the clinical models were constructed through univariate and multivariate logistic regression. Kaplan-Meier survival analysis and log-rank tests were conducted to compare the overall survival time between different TSR groups. RESULTS: To differentiate low TSR from high TSR, the deep learning models based on ShuffulNetV2, Xception, MobileNetV3, and ResNet18 achieved AUCs of 0.846, 0.924, 0.930, and 0.941, respectively, outperforming the radiomics models based on SVM, KNN, RF, and LR with AUCs of 0.739, 0.717, 0.763, and 0.756, respectively. Resnet 18 achieved the best predictive performance. The clinical model based on T stage alone performed worse than deep learning models and radiomics models. The survival analysis based on 142 of the 207 patients demonstrated that patients with low TSR had longer overall survival. CONCLUSIONS: Deep learning models demonstrate feasibility and superiority over radiomics in differentiating TSR in PDAC. The tumor stroma ratio in the PDAC microenvironment plays a significant role in determining prognosis. CRITICAL RELEVANCE STATEMENT: The objective was to compare the feasibility and effectiveness of automatic deep learning networks and radiomics models in identifying the tumor-stroma ratio in pancreatic ductal adenocarcinoma. Our findings demonstrate deep learning models exhibited superior performance compared to traditional radiomics models. KEY POINTS: • Deep learning demonstrates better performance than radiomics in differentiating tumor-stroma ratio in pancreatic ductal adenocarcinoma. • The tumor-stroma ratio in the pancreatic ductal adenocarcinoma microenvironment plays a protective role in prognosis. • Preoperative prediction of tumor-stroma ratio contributes to clinical decision-making and guiding precise medicine.

Neutrophil Extracellular Traps Induce Pyroptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the NF-κB/Caspase 3/GSDME Pathway.

Rheumatoid arthritis (RA) is an enduring, progressive autoimmune disorder. Abnormal activation of fibroblast-like synoviocytes (FLSs) has been proposed as the initiating factor for inflammation of the synovium and bone destruction. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA, histones, and granule proteins, are involved in the development of RA in multiple aspects. Pyroptosis, gasdermin-mediated inflammatory programmed cell death, plays a vital function in the etiopathogenesis of RA. However, the exact mechanism underlying NETs-induced pyroptosis in FLSs of RA and its impact on cellular pathogenic behavior remain undefined. In this study, we demonstrated that gasdermin E (GSDME) expression was upregulated in RA plasma and synoviums, which was positively correlated with the elevated cell-free DNA (cfDNA) and citrullinated histone 3 (Cit H3) levels in the plasma. Additionally, in vitro experiments have shown that NETs triggered caspase 3/GSDME-mediated pyroptosis in RA-FLSs, characterized by decreased cell viability, cell membrane blebbing, and rupture, as well as increased levels of pyroptosis-related proteins and pro-inflammatory cytokines. Again, silencing GSDME significantly inhibited pyroptosis and suppressed the migration, invasion, and secretion of pro-inflammatory cytokines in RA-FLSs. Furthermore, we also found that the nuclear factor-kappa B (NF-κB) pathway, serving as an upstream mechanism, was involved in FLS pyroptosis. In conclusion, our investigation indicated that NETs could induce RA-FLS pyroptosis and facilitate phenotypic transformation through targeting the NF-κB/caspase 3/GSDME axis. This is the first to explore the crucial role of NETs-induced FLS pyroptosis in the progression of RA, providing novel targets for the clinical management of refractory RA.

How I do it? Uniportal full-endoscopic transforaminal lumbar interbody fusion with a complete reduction for L5 isthmic grade 2 spondylolisthesis.

BACKGROUND: Endoscopic transforaminal lumbar interbody fusion (endo-TLIF) with bilateral percutaneous pedicle screw fixation is an emerging option for low-grade spondylolisthesis. However, uniportal full endo-TLIF with a complete reduction for high-grade spondylolisthesis is challenging. METHODS: We attempted uniportal endo-TLIF for L5 isthmic grade 2 spondylolisthesis with a complete reduction, and have described the procedures, with a discussion of the indications, limitations, potential complications, and ways to avoid complications. CONCLUSION: We had successfully completed a perfect reduction of L5 isthmic grade 2 spondylolisthesis via uniportal endo-TLIF with bilateral pedicle screw fixation. Uniportal endo-TLIF is suitable for isthmic grade 2 spondylolisthesis.

Pharmacokinetics and tissue distribution of four major bioactive components of Cynanchum auriculatum extract: a UPLC-MS/MS study in normal and functional dyspepsia rats.

Introduction: Cynanchum auriculatum (CA) is usually used to treat digestive disorders, such as anorexia, enteritis, dysentery, and indigestion. Functional dyspepsia (FD) is characterized by a group of symptoms associated with the gastroduodenal region. Recent pharmacological studies have demonstrated the efficacy of CA for treating FD. However, the pharmacokinetics (PK) and tissue distribution of CA in physiological and FD states is still unclear. The present study aimed to clarify the differences in PK parameters and tissue distribution of the four major active components of CA (baishouwu benzophenone, deacylmet-aplexigenin, qingyangshengenin, and syringic acid) under both physiological and FD states. Methods: For this, normal and FD rats were orally administered 10 mg/kg CA extract. Then, plasma and tissue (heart, liver, spleen, lung, kidney, brain, stomach, and small intestine) samples were obtained. The four active components of CA in rat plasma and tissues were quantified by developing and validating a fast and reliable ultra-high-performance liquid chromatography-mass spectrometry method. Results: The area under the plasma concentration-time curve from time zero to time t (AUC0-t) of baishouwu benzophenone was significantly lower in the FD group than in the normal group (p < 0.01). The FD group had significantly lower (p < 0.001) apparent volume of distribution and plasma clearance of qing-yangshengenin and significantly higher (p < 0.05) AUC0-t of deacylmetaplexigenin and qingyangshengenin. The four active components were rapidly distributed into various tissues, and the main target organs of CA activity were the stomach and small intestine. In addition, baishouwu benzophenone, deacylmetaplexigenin, and qingyangshengenin could cross the blood-brain barrier, indicating that the brain may be another target organ in the treatment of FD. Discussion: These results indicate that the pathological state of FD alters the PK behavior and tissue distribution characteristics of baishouwu benzophenone, deacylmetaplexigenin, qingyangshengenin, and syringic acid in the CA extract, providing an experimental basis for the role of CA in FD treatment.

Symptom clusters and their impact on quality of life among Chinese patients with lung cancer: A cross-sectional study.

PURPOSE: To investigate the symptom clusters of Chinese patients with lung cancer, and explore their impact on quality of life (QoL) and each of its functioning. METHOD: A cross-sectional study was conducted between October 2022 and April 2023 among 219 lung cancer patients at a general hospital in Sichuan Province. Data were collected using a general information questionnaire, the MD Anderson Symptom Inventory, and the EORTC QLQ-C30. R within the RStudio platform was used to conduct descriptive statistics, exploratory factor analysis and multiple regression analysis. RESULTS: Psychoneurological, respiratory, gastrointestinal and fatigue-related symptom clusters were identified, each of which was significantly negatively correlated with overall QoL, global health status/QoL and each functioning. The respiratory (ß = -0.60, P = 0.02) and fatigue-related symptom cluster (ß = -0.86, P = 0.02) were predictors of global health status/QoL; the fatigue-related symptom cluster predicted physical (ß = -1.68, P < 0.01), role (ß = -1.63, P < 0.01) and cognitive functioning (ß = -1.45, P < 0.01); the psychoneurological symptom cluster was a predictor of patients' emotional functioning (ß = -1.26, P < 0.01); and the psychoneurological (ß = -0.81, P < 0.01) and gastrointestinal symptom cluster (ß = -0.60, P = 0.05) predicted social functioning. CONCLUSIONS: Respiratory and fatigue-related symptom clusters were strong predictors of global health status/QoL; fatigue-related, psychoneurological and gastrointestinal symptom clusters had a negative impact on patients' functioning. Nurse practitioners should pay more attention to monitoring respiratory and fatigue-related symptom clusters to identify high-risk populations in time, and tailored interventions based on symptom clusters are needed to synergistically reduce the symptom burden, thereby improving patients' QoL.

A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800mg/m2 gemcitabine, and 25mg/m2 cisplatin every 3 weeks. The primary endpoint was progressive free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 (95% CI, 5.4-13.7) months and 16.4 (95% CI, 10.9-23.6) months, respectively. The most common treatment-related adverse events at ≥3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that CEA levels could monitor patients' survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in PD-1+ cells (p= 0.032) were observed in the response patients. Conclusion: In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Characterization of Anxiety-Like Behaviors and Neural Circuitry following Chronic Moderate Noise Exposure in Mice.

BACKGROUND: Commonly encountered nontraumatic, moderate noise is increasingly implicated in anxiety; however, the neural substrates underlying this process remain unclear. OBJECTIVES: We investigated the neural circuit mechanism through which chronic exposure to moderate-level noise causes anxiety-like behaviors. METHODS: Mice were exposed to chronic, moderate white noise [85 decibel (dB) sound pressure level (SPL)], 4 h/d for 4 wk to induce anxiety-like behaviors, which were assessed by open field, elevated plus maze, light-dark box, and social interaction tests. Viral tracing, immunofluorescence confocal imaging, and brain slice patch-clamp recordings were used to characterize projections from auditory brain regions to the lateral amygdala. Neuronal activities were characterized by in vivo multielectrode and fiber photometry recordings in awake mice. Optogenetics and chemogenetics were used to manipulate specific neural circuitry. RESULTS: Mice chronically (4 wk) exposed to moderate noise (85 dB SPL, 4 h/d) demonstrated greater neuronal activity in the lateral amygdala (LA), and the LA played a critical role in noise-induced anxiety-like behavior in these model mice. Viral tracing showed that the LA received monosynaptic projections from the medial geniculate body (MG) and auditory cortex (ACx). Optogenetic excitation of the MG→LA or ACx→LA circuits acutely evoked anxiety-like behaviors, whereas their chemogenetic inactivation abolished noise-induced anxiety-like behavior. Moreover, mice chronically exposed to moderate noise were more susceptible to acute stress, with more neuronal firing in the LA, even after noise withdrawal. DISCUSSION: Mice exposed to 4 wk of moderate noise (85 dB SPL, 4 h/d) demonstrated behavioral and physiological differences compared to controls. The neural circuit mechanisms involved greater excitation from glutamatergic neurons of the MG and ACx to LA neurons under chronic, moderate noise exposure, which ultimately promoted anxiety-like behaviors. Our findings support the hypothesis that nontraumatic noise pollution is a potentially serious but unrecognized public health concern. https://doi.org/10.1289/EHP12532.

Exosomal miR-222-3p contributes to castration-resistant prostate cancer by activating mTOR signaling.

Despite the clinical benefits of androgen deprivation therapy, most patients with advanced androgen-dependent prostate cancer (ADPC) eventually relapse and progress to lethal androgen-independent prostate cancer (AIPC), also termed castration-resistant prostate cancer (CRPC). MiRNAs can be packaged into exosomes (Exos) and shuttled between cells. However, the roles and mechanisms of exosomal miRNAs involved in CRPC progression have not yet been fully elucidated. Here, we find that miR-222-3p is elevated in AIPC cells, which results in remarkable enhancement of cell proliferation, migration, and invasion ability. Furthermore, Exos released by AIPC cells can be uptaken by ADPC cells, thus acclimating ADPC cells to progressing to more aggressive cell types in vitro and in vivo through exosomal transfer of miR-222-3p. Mechanistically, Exos-miR-222-3p promoted ADPC cells transformed to AIPC-like cells, at least in part, by activating mTOR signaling through targeting MIDN. Our results show that AIPC cells secrete Exos containing miRNA cargo. These cargos can be transferred to ADPC cells through paracrine mechanisms that have a strong impact on cellular functional remodeling. The current work underscores the great therapeutic potential of targeting Exo miRNAs, either as a single agent or combined with androgen receptor pathway inhibitors for CRPC treatment.