House dust mite allergen Der f 2 drives IL-6 and GM-CSF expression in airway epithelial cells via p38 MAPK/NF-κB signaling.

OBJECTIVE: Der f 2, a major allergen derived from Dermatophagoides farinae, is a leading cause of allergic asthma. IL-6 and GM-CSF play essential roles in the exacerbation of asthma. However, the mechanical act by which Der f 2 mediates the expression of IL-6, IL-8, and GM-CSF in airway epithelial cells remains incompletely elucidated. Herein, we aimed to explore the effect of Der f 2 on IL-6 and GM-CSF expression in the human airway epithelial cell BEAS-2B and A549. METHODS: Recombinant Der f 2 (rDf2) was acquired using Pichia pastoris. BEAS-2B and A549 cells were used as cell model. The expression of genes and proteins and the involvement of the signaling cascade were assessed using RT-PCR, quantitative real-time PCR (qPCR), Western blotting, and ELISA, respectively. RESULTS: Our findings showed that rDf2 significantly induced mRNA expression and protein production of IL-6 and GM-CSF in BEAS-2B and A549 cells. In contrast, rDf2 did not influence IL-8 expression or production in both cells. Mechanistic studies revealed that rDf2 triggered activation of the p38 MAPK and JNK. Inhibition of p38, but not JNK, significantly attenuated rDf2-induced IL-6 and GM-CSF expression and production. CONCLUSION: This study demonstrates that Der f 2 promotes the expression and production of the pro-inflammatory cytokines IL-6 and GM-CSF in airway epithelial cells via activation of the p38 signaling pathway. These findings provide insights into the molecular mechanisms that Der f 2 may exacerbate airway inflammation.

Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis.

Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.

The Impact of Relocation Patterns on Psychological Stress.

This study investigated how relocation patterns affect disaster survivors' psychological stress on the diverse durations and spaces of relocation. It analyzed a 10-year data set of 1,236 families affected by 2009's Typhoon Morakot in Taiwan, identifying six relocation patterns through dynamic time warping (DTW). A hierarchical linear model was utilized, revealing the discernible impacts of environmental factors, sociocultural factors, and family-level socioeconomic factors on psychological stress. The study revealed that survivors who quickly found stable residences after the disaster initially experienced lower stress levels, but in the long term, their stress increased. Conversely, those with unstable residences experienced higher initial stress but lower long-term stress. Comparing similar patterns, we found that survivors who had more time for preparation and who sought opportunities, coped, or adapted to secondary stressors before long-distance relocation faced lower stress levels. These findings suggest that relocation patterns have a greater impact on the psychosocial stress of disaster survivors than time or relocation distance.

Quantification Quality Control Emerges as a Crucial Factor to Enhance Single-Cell Proteomics Data Analysis.

Mass spectrometry (MS)-based single-cell proteomics (SCP) provides us the opportunity to unbiasedly explore biological variability within cells without the limitation of antibody availability. This field is rapidly developed with the main focuses on instrument advancement, sample preparation refinement, and signal boosting methods; however, the optimal data processing and analysis are rarely investigated which holds an arduous challenge because of the high proportion of missing values and batch effect. Here, we introduced a quantification quality control to intensify the identification of differentially expressed proteins (DEPs) by considering both within and across SCP data. Combining quantification quality control with isobaric matching between runs (IMBR) and PSM-level normalization, an additional 12% and 19% of proteins and peptides, with more than 90% of proteins/peptides containing valid values, were quantified. Clearly, quantification quality control was able to reduce quantification variations and q-values with the more apparent cell type separations. In addition, we found that PSM-level normalization performed similar to other protein-level normalizations but kept the original data profiles without the additional requirement of data manipulation. In proof of concept of our refined pipeline, six uniquely identified DEPs exhibiting varied fold-changes and playing critical roles for melanoma and monocyte functionalities were selected for validation using immunoblotting. Five out of six validated DEPs showed an identical trend with the SCP dataset, emphasizing the feasibility of combining the IMBR, cell quality control, and PSM-level normalization in SCP analysis, which is beneficial for future SCP studies.

New infundibulopelvic angle measurement method can predict stone-free rates following retrograde intrarenal surgery.

To enhance the accuracy of predicting stone-free rates after retrograde intrarenal surgery, we devised a novel approach to assess the renal infundibulopelvic angle. We conducted a retrospective review of patient records for those who underwent retrograde intrarenal surgery for renal stones between April 2018 and August 2019. Patient demographics, stone characteristics, and perioperative data were recorded. Subsequently, we introduced a modified angle measurement called the pelvic stone angle and evaluated its predictive performance for stone-free rates by comparing it with the traditional method in scoring systems. A total of 43 individuals were included in this study. Notable differences in stone burden and Hounsfield unit measurements were found between stone-free and non-stone-free patients. The pelvic stone angle demonstrated a good model fit when used in scoring systems, performing equally well as the conventional approach. The area under the receiver operating characteristic curve for the R.I.R.S. scoring system using the pelvic stone angle and the conventional approach did not show a significant difference. In conclusion, the predictive ability of the pelvic stone angle for stone-free rates was comparable to the old measurement method. Moreover, scoring systems using the pelvic stone angle exhibited a better model fit than those using the conventional approach.

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores.

BACKGROUND: This study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. METHODS: 341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. RESULTS: Upgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. CONCLUSIONS: Smaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

Lipid Profiles Impact on the Oncologic Outcome of Upper Tract Urothelial Carcinoma.

Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.

Trends and Changes in Intensive Care Use for Patients With Heart Failure in the Last Month of Life.

A good death is a human right. Unfortunately, patients with chronic heart failure (CHF) in the terminal stage still receive inappropriate life-sustaining treatment before death. There is limited understanding of the status of intensive care unit (ICU) admission, mechanical ventilation (MV), cardiopulmonary resuscitation (CPR), and even extracorporeal membrane oxygenation (ECMO) for patients with CHF before death, as well as their use of hospice-related services. This study investigated the trends and trend changes in intensive procedures and hospice-related services for patients with CHF in the last month of life. This population-based retrospective observational study included 25 375 patients with CHF from the National Health Insurance research database in Taiwan and collected information on their intensive treatments during the last month of life. We computed intensive treatment utilization rates and analyzed the trends and trend changes via joinpoint regression. The average percentage of patients with CHF admitted to ICUs was 53.27% (n = 13 516). A total of 327 (1.29%) patients with CHF received ECMO. The percentages of patients receiving MV (54.3%'41.5%) and CPR (41.5%'17%) decreased over time. Conversely, the percentage of ECMO use (0.52%'1.78%) increased. However, only 222 (0.87%) patients with CHF received hospice care in the last month of life between 2001 and 2013. The rates of ICU admission and life-sustaining treatment among patients with CHF in the month before death remain high, and hospice-related services remain inadequate. This study highlights the need for research and training in providing palliative and hospice care for patients with CHF.

Female showed favorable left ventricle hypertrophy regression during post-TAVR follow-up.

Transcatheter aortic valve replacement (TAVR) is a well-established procedure using a catheter-introduced valve prosthesis for patients with severe aortic stenosis (AS). This retrospective study investigated sex-related differences in pre- and post-TAVR clinical and hemodynamic outcomes and analyzed data of the first 100 cases at Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) between December 2013 and December 2021. Baseline characteristics, procedural outcomes, mortality rates, and echocardiographic parameters were analyzed and compared between sexes. Among the 100 patients, male (46%) and female (54%) were of similar age (mean age, male 86.0 years vs. female 84.5 years) and of the same severity of AS (mean pressure gradient, male 47.5 mmHg vs. female 45.7 mmHg) at the time receiving the TAVR procedure. Women had smaller aortic valve areas calculated by continuity equation (0.8 ± 0.3 cm2 vs. 0.7 ± 0.2 cm2, p < 0.001). In addition, women had better left ventricle ejection fraction (59.6 ± 14.0% vs. men 54.7 ± 17.2%, p < 0.01). In the post-TAVR follow-up, regression of left ventricle mass and dimension was better in women than in men. None of the patient died within 30 days after the procedure, and women tended to have a more favorable survival than men (2-year mortality and overall mortality rate in 8.3 year, women 9.1% and 22.2% vs. men 22.2% and 34.8%; p = 0.6385 and 0.1277, respectively). In conclusion, the sex-based difference in post-TAVR regression of LV remodeling suggests a need for sex-based evaluation for patients with severe AS and their post TAVR follow-up.

A newly evolved rice-specific gene JAUP1 regulates jasmonate biosynthesis and signalling to promote root development and multi-stress tolerance.

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources.

The Oncological and Functional Prognostic Value of Unconventional Histology of Prostate Cancer in Localized Disease Treated with Robotic Radical Prostatectomy: An International Multicenter 5-Year Cohort Study.

BACKGROUND AND OBJECTIVE: The impact of prostate cancer of unconventional histology (UH) on oncological and functional outcomes after robot-assisted radical prostatectomy (RARP) and adjuvant radiotherapy (aRT) receipt is unclear. We compared the impact of cribriform pattern (CP), ductal adenocarcinoma (DAC), and intraductal carcinoma (IDC) in comparison to pure adenocarcinoma (AC) on short- to mid-term oncological and functional results and receipt of aRT after RARP. METHODS: We retrospectively collected data for a large international cohort of men with localized prostate cancer treated with RARP between 2016 and 2020. The primary outcomes were biochemical recurrence (BCR)-free survival, erectile and continence function. aRT receipt was a secondary outcome. Kaplan-Meier survival and Cox regression analyses were performed. KEY FINDINGS AND LIMITATIONS: A total of 3935 patients were included. At median follow-up of 2.8 yr, the rates for BCR incidence (AC 10.7% vs IDC 17%; p < 0.001) and aRT receipt (AC 4.5% vs DAC 6.3% [p = 0.003] vs IDC 11.2% [p < 0.001]) were higher with UH. The 5-yr BCR-free survival rate was significantly poorer for UH groups, with hazard ratios of 1.67 (95% confidence interval [CI] 1.16-2.40; p = 0.005) for DAC, 5.22 (95% CI 3.41-8.01; p < 0.001) for IDC, and 3.45 (95% CI 2.29-5.20; p < 0.001) for CP in comparison to AC. Logistic regression analysis revealed that the presence of UH doubled the risk of new-onset erectile dysfunction at 1 yr, in comparison to AC (grade group 1-3), with hazard ratios of 2.13 (p < 0.001) for DAC, 2.14 (p < 0.001) for IDC, and 2.01 (p = 0.011) for CP. Moreover, CP, but not IDC or DAC, was associated with a significantly higher risk of incontinence (odds ratio 1.97; p < 0.001). The study is limited by the lack of central histopathological review and relatively short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS: In a large cohort, UH presence was associated with worse short- to mid-term oncological outcomes after RARP. IDC independently predicted a higher rate of aRT receipt. At 1-yr follow-up after RP, patients with UH had three times higher risk of erectile dysfunction post RARP; CP was associated with a twofold higher incontinence rate. PATIENT SUMMARY: Among patients with prostate cancer who undergo robot-assisted surgery to remove the prostate, those with less common types of prostate cancer have worse results for cancer control, erection, and urinary continence and a higher probability of receiving additional radiotherapy after surgery.

A comparison of S.T.O.N.E nephrolithometry scoring system, Guy's stone score, and Seoul National University Renal Stone Complexity (S-ReSC) in predicting mini-PCNL stone-free rate.

The main goal of the study is to evaluate the three stone scoring systems (S.T.O.N.E nephrolithometry scoring system (STONE), Guy's stone score (GSS) and Seoul National University Renal Stone Complexity (S-ReSC)) for the stone-free rate (SFR) of mini-PCNL. We retrospectively analyzed 72 patients who received mini-PCNL from February 2018 to October 2020. The SFR, complication rates, hospitalization days and recurrence rates were analyzed using three stone scoring systems. The result showed statistical significance in the association between scoring system and stone-free (STONE: OR 95%CI 0.409 (0.221-0.759), p = 0.0045; S-ReSC OR 95%CI 0.633 (0.401-0.999), p = 0.0497), but not GSS (OR 95%CI 0.776 (0.397-1.516), p = 0.4581). After adjusting the potential confounding factors, the area under curve (AUC) of STONE, GSS, and S-ReSC was 0.86, 0.78, and 0.81, respectively, and Akaike information criterion (AIC) of STONE, GSS, and S-ReSC was 64.65, 74.89, and 69.92, respectively. The accuracy rate of STONE, GSS, and S-ReSC was 0.81, 0.75, and 0.79, respectively. There was no statistically difference of predicting stone recurrence (p = 0.46, 0.53, 0.86), complications (p = 0.74, 0.51, 0.16) and hospitalization days (p = 0.77, 0.86, 0.87) in STONE, GSS, and S-ReSC, respectively. In conclusion, both the STONE and S-ReSC stone scoring systems are viable for predicting the SFR following mini-PCNL, especially after variable adjustment with the STONE system demonstrating superiority over S-ReSC.

Isolation and characterizations of multidrug-resistant human cancer cells by a biodegradable nano-sensor.

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging. DNCP-MB - possess a surface potential of -8 mV and a size of 150 nm - demonstrated effective delivery of MB, remarkable selectivity towards the selected intracellular mRNA targets, and low cytotoxicity. Following DNCP transfection, fluorescence-activated cell sorting (FACS) was employed to differentiate MCF-7 cells into two distinct sub-populations: the Top 10 cells with a high level of MDR gene expression and the Bottom 10 cells with a low level of MDR gene expression, which represent inherent drug-resistant and non-drug-resistant cells, respectively. Intriguingly, we observed a positive correlation between elevated MDR1 mRNA expression and increased migration, enhanced proliferation rate, and tighter spheroid formation. Moreover, we conducted RNA sequencing analysis on the Top 10, Bottom 10, and MCF-7/ADR cells. The findings revealed a notable disparity in the gene ontology enrichment analysis of differentially expressed genes between the Top 10 and Bottom 10 cells when compared to the Bottom 10 and MCF-7/ADR cells. This novel approach provides a promising avenue for isolating inherent drug-resistant cells and holds significant potential in unraveling the mechanisms underlying inherent drug resistance.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE). MATERIALS AND METHODS: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test. RESULTS: Based on our research, ureter tumor, female, smoking history, age (< 70 years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR. CONCLUSION: Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients.

Pb(NO3 )2 induces cell apoptosis through triggering of reactive oxygen species accumulation and disruption of mitochondrial function via SIRT3/SOD2 pathways.

Lead (Pb) is nonbiodegradable and toxic to the lungs. To investigate the potential mechanisms of Pb-induced reactive oxygen species (ROS) accumulation and cell death in the lungs, human non-small lung carcinoma H460 cells were stimulated with Pb(NO3 )2 in this study. The results showed that Pb(NO3 )2 stimulation increased cell death by inducing cell apoptosis which showed a reduced Bcl-2 expression and an enhanced caspase 3 activation. Pb(NO3 )2 also caused the production of H2 O2 in H460 cells that triggering the buildup of ROS and mitochondrial membrane potential loss. We found that Pb(NO3 )2 modulates oxidoreductive activity through reduced the glutathione-disulfide reductase and glutathione levels in Pb(NO3 )2 -exposed H460 cells. Furthermore, the superoxide dismutase (SOD) upstream molecule sirtuin 3 (SIRT3) was increased with Pb(NO3 )2 dose. Collectively, these results demonstrate that Pb(NO3 )2 promotes lung cell death through SIRT3/SOD-mediated ROS accumulation and mitochondrial dysfunction.

Treatment of primary aldosteronism: Clinical practice guidelines of the Taiwan Society of Aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and one of the few medical diseases that can be cured by surgery. Excessive aldosterone secretion is highly associated with cardiovascular complications. Many studies have shown that patients with unilateral PA treated with surgery have better survival, cardiovascular, clinical, and biochemical outcomes than those who receive medical treatment. Consequently, laparoscopic adrenalectomy is the gold standard for treating unilateral PA. Surgical methods should be individualized according to the patient's tumor size, body shape, surgical history, wound considerations, and surgeon's experience. Surgery can be performed through a transperitoneal or retroperitoneal approach, and via a single-port or multi-port laparoscopic approach. However, total or partial adrenalectomy remains controversial in treating unilateral PA. Partial excision will not completely eradicate the disease and is prone to recurrence. Mineralocorticoid receptor antagonists should be considered for patients with bilateral PA or patients who cannot undergo surgery. There are also emerging alternative interventions, including radiofrequency ablation and transarterial adrenal ablation, for which data on long-term outcomes are currently lacking. The Task Force of Taiwan Society of Aldosteronism developed these clinical practice guidelines with the aim of providing medical professionals with more updated information on the treatment of PA and improving the quality of care.

The Relationship between Allergic Disease and Sexual Dysfunction: A Scoping Review.

INTRODUCTION: Sexual dysfunction (SD) and allergic disease are common health concerns worldwide and bear a potential relationship. This scoping review is conducted to analyze the currently available data regarding the associations between these two health issues. METHODS: A comprehensive literature search was performed in the databases of PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to retrieve studies that were published before January 2023. A narrative synthesis was conducted to analyze the effects of allergic diseases on SD based on the evaluation of the Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF). RESULTS: Twelve observational studies were included after the selection process. The results generally suggested lower FSFI or IIEF scores in patients with asthma, allergic rhinitis, allergic rhinoconjunctivitis, and urticaria compared to the healthy control groups. The underlying factors of this relationship could be inflammation, psychological factors, hormonal changes, sleep disorders, sexual behavior-related allergic reactions, social economic status, and the use of medications. CONCLUSION: SD and allergic disease are interrelated based on the extant literature. This scoping review provides insights into the clinical implications of both entities, while more research studies are warranted to further elucidate this complex relationship.

Loss of MTA2-mediated downregulation of PTK7 inhibits hepatocellular carcinoma metastasis progression by modulating the FAK-MMP7 axis.

The expression of metastasis tumor-associated protein 2 (MTA2) and protein tyrosine kinase 7 (PTK7) is associated with hepatocellular carcinoma (HCC) progression. However, the functional effect and mechanism through which MTA2 regulates PTK7-mediated HCC progression remains unclear. Here, we found that MTA2 knockdown significantly down-regulated PTK7 expression in HCC cells (SK-Hep-1 and PLC/PRF/5). Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases show that the PTK7 expression level was higher in HCC tissues than in normal liver tissues. In HCC patients, the PTK7 expression level clearly correlated with tumor stage and grade, lower overall survival (OS) correlated positively with MTA2 level, and PTK7 expression acted as a downstream factor for MTA2 expression. In addition, matrix metalloproteinase 7 (MMP7) expression was closely regulated by PTK7, and the mRNA and protein expression levels of MTA2 and PTK7 correlated positively with lower OS. MMP7 downregulation by PTK7 knockdown clearly decreased the migration and invasion abilities of HCC cells. In HCC cells, recombinant human MMP7 reversed the PTK7 knockdown-induced suppression of migration and invasion. Furthermore, deactivation of FAK using siFAK or FAK inhibitor (PF-573228, PF) synergistically contributed to PTK7 knockdown-inhibited FAK activity, MMP7 expression, and the migration and invasion abilities of HCC cells. Collectively, our findings show that PTK7 mediates HCC progression by regulating the MTA2-FAK-MMP7 axis and may be a diagnostic value for HCC patients.

Age-dependent extinction and the neutral theory of biodiversity.

Red Queen (RQ) theory states that adaptation does not protect species from extinction because their competitors are continually adapting alongside them. RQ was founded on the apparent independence of extinction risk and fossil taxon age, but analytical developments have since demonstrated that age-dependent extinction is widespread, usually most intense among young species. Here, we develop ecological neutral theory as a general framework for modeling fossil species survivorship under incomplete sampling. We show that it provides an excellent fit to a high-resolution dataset of species durations for Paleozoic zooplankton and more broadly can account for age-dependent extinction seen throughout the fossil record. Unlike widely used alternative models, the neutral model has parameters with biological meaning, thereby generating testable hypotheses on changes in ancient ecosystems. The success of this approach suggests reinterpretations of mass extinctions and of scaling in eco-evolutionary systems. Intense extinction among young species does not necessarily refute RQ or require a special explanation but can instead be parsimoniously explained by neutral dynamics operating across species regardless of age.

Impact of Region-of-Interest Size on the Diagnostic Performance of Shear Wave Elastography in Differentiating Thyroid Nodules.

This study investigated the impact of different region-of-interest (ROI) sizes (Max, 1 mm, and 2 mm) on shear wave elastography (SWE) in differentiating between malignant and benign thyroid nodules. The study cohort comprised 129 thyroid nodules (50 malignant, 79 benign) and 78 normal subjects. Diagnostic efficacy was assessed through pairwise comparisons of area under the curve (AUC) values in receiver operating characteristic analysis by using DeLong's test. Our results indicated significant differences in all SWE elasticity metrics between the groups, with malignant nodules exhibiting higher values than benign nodules (p < 0.05). Smaller ROIs (1 and 2 mm) were found to outperform the max ROI in terms of diagnostic accuracy, particularly for the Emax and Emin elasticity metrics. Emax(1mm) had the highest diagnostic accuracy, with an AUC of 0.883, sensitivity of 74.0%, and specificity of 86.1%. This study underscores the significant influence of ROI size selection on the diagnostic performance of SWE, offering valuable insights for future research and clinical applications in thyroid nodule assessment.