Autophagy Regulates Age-Related Jawbone Loss via LepR+ Stromal Cells.

Bone aging and decreased autophagic activity are related but poorly explored in the jawbone. This study aimed to characterize the aging jawbones and jawbone-derived stromal cells (JBSCs) and determine the role of autophagy in jawbone mass decline. We observed that the jawbones of older individuals and mice exhibited similar age-related bone loss. Furthermore, leptin receptor (LepR)-lineage cells served as the primary source for in vitro cultured and expanded JBSCs, referred to as LepR-Cre+/JBSCs. RNA-sequencing data from the jawbones and LepR-Cre+/JBSCs showed the upregulated expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during aging. Through single-cell transcriptomics, we identified a decrease in the proportion of osteogenic lineage cells and the activation of the PI3K/AKT pathway in LepR-lineage cells in aging bone tissues. Reduced basal autophagic activity, diminished autophagic flux, and decreased osteogenesis occurred in the jawbones and LepR-Cre+/JBSCs from older mice (O-mice; O-JBSCs). Pharmacologic and constitutive autophagy activation alleviated the impaired osteogenesis in O-JBSCs. In addition, the suppression of mTOR-induced autophagy improved the aging phenotype of O-JBSCs. The activation of autophagy in LepR-Cre+/JBSCs using chemical autophagic activators reduced the alveolar bone resorption in O-mice. Therefore, our study demonstrated that ATG molecules and pathways are crucial in jawbone aging, providing novel approaches to understanding age-related jawbone loss.

[A consistency comparison between next-generation sequencing and the FISH method for gene rearrangement detection in B-cell lymphomas].

Objective: To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement. Methods: From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed. Results: Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement (P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions: NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.

[Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province].

Objective: To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province. Methods: This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized. Results: Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion: Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Genome-wide detection of runs of homozygosity and heterozygosity in Tunchang pigs.

Tunchang pigs, mainly distributed throughout Hainan Province of China, are well-known for their superior meat quality, crude feed tolerance, and adaptability to high temperatures and humidity. Runs of homozygosity (ROH) can provide valuable information about the inbreeding coefficient in individuals and selection signals that may reveal candidate genes associated with key functional traits. Runs of heterozygosity (ROHet) are commonly associated with balance selection, which can help us understand the adaptive evolutionary history of domestic animals. In this study, we investigated ROHs and ROHets in 88 Tunchang pigs. We also compared the estimates of inbreeding coefficients in individuals calculated based on four methods. In summary, we detected a total of 16 ROH islands in our study, and 100 genes were found within ROH regions. These genes were correlated with economically important traits such as reproduction (e.g., SERPIND1, HIRA), meat quality (e.g., PI4KA, TBX1), immunity (e.g., ESS2, RANBP1), adaption to heat stress (TXNRD2 and DGCR8), and crude food tolerance (TRPM6). Moreover, we discovered 18 ROHet islands harbouring genes associated with reproduction (e.g., ARHGEF12, BMPR2), immune system (e.g., BRD4, DNMT3B). These findings may help us design effective breeding and conservation strategies for this unique breed.

Multi-machine learning methods to predict spatial variation characteristics of total nitrogen at watershed scale: Evidences from the largest watershed (Yangtze River Watershed), Asian.

Nitrogen pollution has emerged as a significant threat to the health of global river systems, garnering considerable attention. However, numerous challenges persist in understanding the characteristics and predicting the spatial changes of total nitrogen (TN) at the catchment scale. We leveraged data from 530 monitoring sections to calculate a land-use composite index and perform statistical analyses to explore the primary factors influencing nitrogen enrichment in the Yangtze River Watershed. We developed three machine learning models to forecast future TN concentrations at monitoring points. Our results showed that agricultural activities and rainfall were the primary drivers of monthly variations in TN concentrations. The upstream region of the watershed exhibited larger variations in TN concentrations (0.097 to 11.099 mg/L), significantly higher than the middle and downstream areas (0.348 to 6.844 mg/L). Microbial-mediated organic matter decomposition in sediment and changes in land-use were identified as key contributors to regional differences in nitrogen enrichment. Potential nitrogen sources include sediment release, urban sewage, and agricultural fertilization. Random Forest model achieved a prediction accuracy of 77.6 %, surpassing the BP and LSTM models. We identified 37 high-risk areas of nitrogen enrichment, concentrated in the Chengdu-Chongqing, Yunnan-Central urban cluster, and the Chaohu Lake sub-watershed. Increased urban land-use and industrial inputs primarily influenced nitrogen enrichment in the upstream area, while agricultural inputs were the main drivers in the middle and downstream regions. Our multi-machine learning models identified the relationship between TN and influencing factors, providing a reliable method for assessing nitrogen enrichment risk in the watershed.

Water uptake patterns and rooting depths of Tamarix ramosissima in the coppice dunes of the Gurbantünggüt Desert, China: a stable isotope analysis.

Tamarix ramosissima has an important role in stabilizing sand dunes in desert ecosystems. Understanding the water use strategies of T. ramosissima is essential to understand its adaptations on coppice dunes. We utilized the stable isotopes δ2H and δ18O in soil water, groundwater, and xylem water to identify monthly differences in water sources. Additionally. we explored rooting depth using 2H2O as an artificial tracer. In May, T. ramosissima derived 75% of its water from shallow and middle soil layers. In July, it absorbed 90% water from middle and deep soil layers. In August and September, it acquired approximately 80% of its water from deep soil layers. The labelling using 2H as an artificial tracer indicated that the root system of T. ramosissima could reach depths >500 cm in the coppice dunes. 2H absorption was observed at depths of 100, 200, 300 and 400 cm. Soil water is the dominant water source for T. ramosissima in the coppice dunes because groundwater is at depths >30 m. The flexible water-use strategies of T. ramosissima enable it to effectively utilize different available water sources to adapt to the arid environment. These findings improve our understanding of water uptake patterns and drought adaptation strategies of T. ramosissima in the coppice dunes of desert ecosystems.

[Correctly performing manual supragingival scaling exercises-part of a series on basic training in periodontal diagnosis and treatment].

Cultivating dental general doctors who practice standardized periodontal diagnosis and treatment techniques is conducive to the prevention and control of periodontal diseases and the improvement of oral health of our population. Manual supragingival scaling is the most important basic skill of basic periodontal treatment, and it is the basic periodontal diagnosis and treatment technique that every oral general practitioner should know. This article starts from why manual supragingival scaling is important and how to standardize the teaching and training of manual supragingival scaling, and begin with the first chapter of basic periodontal diagnosis and treatment training, to provide reference for promoting the standardized development of periodontology teaching in China.

[Clinical profiles of community-acquired Pseudomonas aeruginosa infections in children].

Objectives: To investigate clinical characteristics, outcomes and antimicrobial resistance of community-acquired Pseudomonas aeruginosa (CAPA) infections in Chinese pediatric patients. Methods: This retrospective study was conducted at 6 tertiary hospitals in China during January 2016 to December 2018. The clinical and microbiological data of CAPA infected hospitalized children in Hainan and in other regions were collected and compared, and the antimicrobial resistance patterns, clinical characteristics and antibiotic therapy were analyzed. Between different groups were compared using the Chi-square test and Mann-Whitney U test. Results: Among 91 patients, 63 cases were males, 28 cases were females, and 74 cases were from Hainan province, 17 cases were from other regians. The age of consultation was 22.5 (5.4, 44.0) months. Twenty-four cases (26%) had underlying diseases. Fever (79 cases (87%)) and cough (64 cases (70%)) were common initial symptoms. Other concomitant symptoms included wheezing 8 cases (9%), diarrhea 3 cases (3%) and vomiting 4 cases (4%). Twenty-eight cases (31%) had organ infections, including pneumonia 22 cases (24%), skin infection 5 cases (5%), meningitis, intra-abdominal infection and upper urinary tract infection each 1 case (1%). The resistance rate of CAPA isolates to cefepime (4% (4/90)), amikacin (1% (1/90)), ciprofloxacin (2% (2/90)) and levofloxacin (1% (1/89)) was low, and to ceftazidime, piperacillin, piperacillin-azobactam, carbapenem was 12% (11/90), 3/16, 18% (10/56) and 6% (5/90), respectively. Antimicrobial combination therapy accounted for 52% (47/91) of empirical therapy and 59% (52/88) of definite therapy. Two cases (2%) were hopeless discharged, and 3 cases (3%) died during hospitalization. The worse prognosis of CAPA infection is significantly different among children in other regions and in Hainan (4/17 vs. 1% (1/74), χ²=9.74, P<0.05). Conclusions: The invasive CAPA-infection has regional difference in incidence and prognosis in China. Clinical symptoms and signs are non-specific. CAPA strains isolated from pediatric patients display low level of resistance to most of the common antipseudomonal antibiotics. The proportion of poor prognostic outcome is lower in Hainan than in other regions.

[Evaluation of visual quality and refractive outcomes of myopia with presbyopia after laser blended vision surgery].

Objective: To investigate the postoperative outcomes and visual quality following laser blended vision (LBV) surgery for the correction of myopia with presbyopia. Methods: This is a prospective study. A total of 50 patients (100 eyes) who underwent LBV surgery for myopia with presbyopia at Beijing Tongren Hospital, Capital Medical University, between August 2021 and March 2022 were included. Uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), best-corrected distance visual acuity (BCDVA), manifest refraction spherical equivalent (MRSE) were measured preoperatively and at 1, 3, 6, 12, and 24 months postoperatively for the dominant eye, non-dominant eye, and both eyes. Effectiveness Index (EI) and Safety Index (SI) were calculated to evaluate refractive outcomes. Accommodation function and contrast sensitivity were assessed to evaluate functional vision. Objective visual quality was assessed using higher-order aberrations (HOAs) and a dual-channel visual quality analysis system. Subjective visual quality was evaluated using a questionnaire. Results: At 24 months postoperatively, the EI and SI for the dominant eye were 1.04±0.23 and 1.14±0.14, respectively, while for the non-dominant eye, they were 0.85±0.21 and 1.06±0.08, respectively. Although there were statistically significant differences in UNVA between the eyes at 1 and 3 months postoperatively (all P<0.05), no significant differences were observed from 6 months onward (all P>0.05). At 6 months postoperatively, the UNVA for the dominant and non-dominant eyes were 0.07±0.13 and 0.03±0.13, respectively, with no significant difference (P>0.05). MRSE showed no significant differences at any follow-up time points up to 24 months. Accommodation function did not decrease compared to preoperative levels at any postoperative follow-up. Increases in HOAs were primarily due to spherical aberrations, and there were no significant differences in objective visual quality before and after surgery. Contrast sensitivity improved significantly at 24 months postoperatively compared to preoperative levels. At 24 months postoperatively, 11 out of 12 patients reported good visual quality in the questionnaire. Conclusions: LBV surgery gradually achieves good binocular blended vision within 6 months postoperatively and demonstrates good safety, efficacy, and stability at 24 months. It maintains good functional vision and visual quality with high postoperative patient satisfaction.

[High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF-ß signaling pathway].

OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TßR1, MMP-2, and MMP-9 in esophageal cancer. RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-ß signaling pathway, and the expressions of MMP-2/MMP-9 and TßR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TßR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. CONCLUSION: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-ß signaling pathway, and its high expression promotes migration of ESCC cells.

[Comparison of quantitative detection of BCR::ABL1 p210 transcript levels: a multicenter study].

Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

[A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults].

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) µIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

[How do female mosquitoes determine the most suitable males for mating?]

More than 80% of the world's populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.

Periodontitis and Chronic Obstructive Pulmonary Disease: A bidirectional Mendelian randomization study.

OBJECTIVE: Observational studies have suggested an association between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD). This study aimed to determine whether there is a causal relationship between CP and COPD incidence. DESIGN: Two­sample Mendelian Randomization (MR) analysis using summary statistics from two genome­wide association studies (GWASs) of European ancestry. Single nucleotide polymorphisms (SNPs) associated with COPD were obtained from the FinnGen database, which included 16,380,382 SNPs. The diagnosis of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2023). We also obtained SNPs associated with CP from the FinnGen database, which included 16,380,378 SNPs. RESULTS: Sixteen eligible SNPs were extracted to analyze the causal effect of CP on COPD incidence. There was no causal correlation between CP and COPD using the inverse variance-weighted method (IVW) (OR=0.97, 95%CI= 0.91-1.05; p=0.482). Seven eligible SNPs were extracted to analyze the causal effect of COPD on CP incidence. Again, there was also no causal correlation between using IVW (OR=1.09, 95%CI=0.93-1.28; p=0.279). CONCLUSION: We did not demonstrate a causal relationship between genetically predicted CP and COPD, or between genetically predicted COPD and CP.

[Unsupervised clustering analysis based on multidimensional features reveals distinct clinical characteristics and associated factors of different phenotypes in patients with chronic rhinosinusitis with nasal polyp].

Objective: To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis. Methods: The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software. Results: Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP. Conclusion: The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

A framework for validating watershed ecosystem service models in the United States using long-term water quality data: Applications with the InVEST Nutrient Delivery (NDR) model in Puerto Rico.

Modeling of watershed Ecosystem Services (ES) processes has increased greatly in recent years, potentially improving environmental management and decision-making by describing the value of nature. ES models may be sensitive to different conditions and, therefore, should ideally be validated against observed data for their use as a decision-support instrument. However, outcomes from such ES modeling are barely validated, making it difficult to assess uncertainties associated with the modeling and justify their actual usefulness to develop generalizable management recommendations. This study proposes a framework for the systematic validation of one of such tools, the InVEST Nutrient Delivery Model (NDR) for nutrient retention estimates. The framework is divided into three stages: 1) running the NDR model inputs, processes, and outputs; 2) building a long-term reference dataset from open access water quality observations; and 3) using the reference data for model calibration and validation. We applied this framework to twenty watersheds in the Commonwealth of Puerto Rico, where data availability resembles thar of watersheds across the United States. Long-term water quality data from monitoring stations facilitated model calibration and validation. Our framework provided a reproducible method to linking the vast monitoring network in the U.S. and its territories for evaluating the InVEST's NDR model performance. Beyond the framework development, this study found that the InVEST NDR model explained 62.7 % and 79.3 % of the variance in the total nitrogen and total phosphorus between 2000 and 2022, respectively, supporting the suitability of the model for watershed scale ecosystem services assessment. The findings can also serve as a reference to support the use of InVEST for other locations in the tropics without publically available monitoring data.

In situ evidence of the magnetospheric cusp of Jupiter from Juno spacecraft measurements.

The magnetospheric cusp connects the planetary magnetic field to interplanetary space, offering opportunities for charged particles to precipitate to or escape from the planet. Terrestrial cusps are typically found near noon local time, but the characteristics of the Jovian cusp are unknown. Here we show direct evidence of Jovian cusps using datasets from multiple instruments onboard Juno spacecraft. We find that the cusps of Jupiter are in the dusk sector, which is contradicting Earth-based predictions of a near-noon location. Nevertheless, the characteristics of charged particles in the Jovian cusps resemble terrestrial and Saturnian cusps, implying similar cusp microphysics exist across different planets. These results demonstrate that while the basic physical processes may operate similarly to those at Earth, Jupiter's rapid rotation and its location in the heliosphere can dramatically change the configuration of the cusp. This work provides useful insights into the fundamental consequences of star-planet interactions, highlighting how planetary environments and rotational dynamics influence magnetospheric structures.