Evolution of the FLOWERING LOCUS T-like genes in angiosperms: a core-Lamiales-specific diversification.

Plant life-history is determined by two transitions, the germination and the flowering times, in which the phosphatidylethanolamine-binding proteins (PEBP) FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) play key regulatory roles. Compared to the highly conserved TFL1-likes, FT-like genes vary in copy numbers significantly in gymnosperms and monocots of the angiosperms, while sporadic duplications can be observed in eudicots. Here, via a systematic analysis of the PEBPs in angiosperms with a special focus on twelve representative species featuring high-quality genomes in the Lamiales order, we identified a successive lineage-specific but systematic expansion of FT-like genes in the families of core Lamiales. The first expansion event generated FT1-likes mainly via a core-Lamiales-specific whole-genome-duplication (cL-WGD), while on the other hand, a likely random duplication produced the FT2-likes in the lineages containing Scrophulariaceae and rest of the core Lamiales. Both FT1- and FT2-like genes were further amplified tandemly in some families. These expanded FT-likes featured highly diverged expression patterns and structural variation, indicating functional diversification. Intriguingly, some core Lamiales contained the relict MOTHER OF FT AND TFL1 like 2 (MFT2) that likely expanded in the common ancestor of angiosperms. Our data showcase the highly dynamic lineage-specific expansion of the FT-like genes, thus provide important and fresh evolutionary insights into the gene-regulatory-network underpinning flowering time diversity in Lamiales, and more generally, in angiosperms.

A deep-learning model for intracranial aneurysm detection on CT angiography images in China: a stepwise, multicentre, early-stage clinical validation study.

BACKGROUND: Artificial intelligence (AI) models in real-world implementation are scarce. Our study aimed to develop a CT angiography (CTA)-based AI model for intracranial aneurysm detection, assess how it helps clinicians improve diagnostic performance, and validate its application in real-world clinical implementation. METHODS: We developed a deep-learning model using 16 546 head and neck CTA examination images from 14 517 patients at eight Chinese hospitals. Using an adapted, stepwise implementation and evaluation, 120 certified clinicians from 15 geographically different hospitals were recruited. Initially, the AI model was externally validated with images of 900 digital subtraction angiography-verified CTA cases (examinations) and compared with the performance of 24 clinicians who each viewed 300 of these cases (stage 1). Next, as a further external validation a multi-reader multi-case study enrolled 48 clinicians to individually review 298 digital subtraction angiography-verified CTA cases (stage 2). The clinicians reviewed each CTA examination twice (ie, with and without the AI model), separated by a 4-week washout period. Then, a randomised open-label comparison study enrolled 48 clinicians to assess the acceptance and performance of this AI model (stage 3). Finally, the model was prospectively deployed and validated in 1562 real-world clinical CTA cases. FINDINGS: The AI model in the internal dataset achieved a patient-level diagnostic sensitivity of 0·957 (95% CI 0·939-0·971) and a higher patient-level diagnostic sensitivity than clinicians (0·943 [0·921-0·961] vs 0·658 [0·644-0·672]; p<0·0001) in the external dataset. In the multi-reader multi-case study, the AI-assisted strategy improved clinicians' diagnostic performance both on a per-patient basis (the area under the receiver operating characteristic curves [AUCs]; 0·795 [0·761-0·830] without AI vs 0·878 [0·850-0·906] with AI; p<0·0001) and a per-aneurysm basis (the area under the weighted alternative free-response receiver operating characteristic curves; 0·765 [0·732-0·799] vs 0·865 [0·839-0·891]; p<0·0001). Reading time decreased with the aid of the AI model (87·5 s vs 82·7 s, p<0·0001). In the randomised open-label comparison study, clinicians in the AI-assisted group had a high acceptance of the AI model (92·6% adoption rate), and a higher AUC when compared with the control group (0·858 [95% CI 0·850-0·866] vs 0·789 [0·780-0·799]; p<0·0001). In the prospective study, the AI model had a 0·51% (8/1570) error rate due to poor-quality CTA images and recognition failure. The model had a high negative predictive value of 0·998 (0·994-1·000) and significantly improved the diagnostic performance of clinicians; AUC improved from 0·787 (95% CI 0·766-0·808) to 0·909 (0·894-0·923; p<0·0001) and patient-level sensitivity improved from 0·590 (0·511-0·666) to 0·825 (0·759-0·880; p<0·0001). INTERPRETATION: This AI model demonstrated strong clinical potential for intracranial aneurysm detection with improved clinician diagnostic performance, high acceptance, and practical implementation in real-world clinical cases. FUNDING: National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Genomes of Meniocus linifolius and Tetracme quadricornis reveal the ancestral karyotype and genomic features of core Brassicaceae.

Brassicaceae represents an important plant family from both a scientific and economic perspective. However, genomic features related to the early diversification of this family have not been fully characterized, especially upon the uplift of the Tibetan Plateau, which was followed by increasing aridity in the Asian interior, intensifying monsoons in Eastern Asia, and significantly fluctuating daily temperatures. Here, we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius (Arabodae; clade D) and Tetracme quadricornis (Hesperodae; clade E), together with genomes representing all major Brassicaceae clades and the basal Aethionemeae. We reconstructed an ancestral core Brassicaceae karyotype (CBK) containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae. We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events, which correlate well with the early divergence of core Brassicaceae. We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1 (TPS1) gene family, which encodes enzymes with essential regulatory roles in flowering time and embryo development. The TPS1s were mainly randomly amplified, followed by expression divergence. Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment.

Deep learning based ultrasound analysis facilitates precise distinction between parotid pleomorphic adenoma and Warthin tumor.

Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.

Meroterpenoids with divers' rings systems from Phyllosticta capitalensis and their anti-inflammatory activity.

Four undescribed sesquiterpene-shikimates (1-4), eight undescribed monoterpene-shikimates (5-12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2-O-C-9' connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 µM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed.

Health-related quality of life and its changes of the Tibetan population in China: based on the 2013 and 2018 National Health Services Surveys.

OBJECTIVE: Health-related quality of life (HRQoL) was an important health outcome measure for evaluating an individual's overall health status. However, there was limited in the literature on HRQoL and its long-term changes of the Tibetan population. This study aimed to assess HRQoL of Tibetan and its changes over time, and explore the differences in HRQoL for residents at different altitudes. DESIGN: Data for the cross-sectional study were extracted from the fifth and sixth waves of the National Health Services Surveys which were conducted in 2013 and 2018. A multistage stratified cluster random sampling strategy was used to select representative participants. SETTING: Tibet Autonomous Region in China. PARTICIPANTS: This study recruited 14 752 participants in 2013 and 13 106 participants in 2018, and after excluding observations with missing values for key variables, 10 247 in 2013 and 6436 in 2018 were included in the study analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The EQ-5D-3L was used to measure participants' HRQoL. RESULTS: The mean health state utility scores of the participants were 0.969±0.078 and 0.966±0.077 in 2013 and 2018, respectively. Pain/discomfort was the most frequently prevalent issue reported in 18.1% and 17.9% of the participants in 2013 and 2018, respectively. Tibetans living 3500-4000 m altitude had the best HRQoL. Age, sex, employment status, educational attainment, chronic disease and weekly physical exercise were influencing factors associated with HRQoL. CONCLUSIONS: The HRQoL of the Tibetan population was lower than the general Chinese population, and decreased over time between 5 years. There were differences in HRQoL among Tibetan at different altitudes, with residents living at 3500-4000 m having the best quality of life. More attention should be paid to those Tibetans who are older, female, unemployed and without formal education.

Arbuscular mycorrhizal fungi enhance active ingredients of medicinal plants: a quantitative analysis.

Medicinal plants are invaluable resources for mankind and play a crucial role in combating diseases. Arbuscular mycorrhizal fungi (AMF) are widely recognized for enhancing the production of medicinal active ingredients in medicinal plants. However, there is still a lack of comprehensive understanding regarding the quantitative effects of AMF on the accumulation of medicinal active ingredients. Here we conducted a comprehensive global analysis using 233 paired observations to investigate the impact of AMF inoculation on the accumulation of medicinal active ingredients. This study revealed that AMF inoculation significantly increased the contents of medicinal active ingredients by 27%, with a particularly notable enhancement observed in flavonoids (68%) and terpenoids (53%). Furthermore, the response of medicinal active ingredients in belowground organs (32%) to AMF was more pronounced than that in aboveground organs (18%). Notably, the AMF genus Rhizophagus exhibited the strongest effect in improving the contents of medicinal active ingredients, resulting in an increase of over 50% in both aboveground and belowground organs. Additionally, the promotion of medicinal active ingredients by AMF was attributed to improvements in physiological factors, such as chlorophyll, stomatal conductance and net photosynthetic rate. Collectively, this research substantially advanced our comprehension of the pivotal role of AMF in improving the medicinal active ingredients of plants and provided valuable insights into the potential mechanisms driving these enhancements.

What is the relationship between health-related quality of life among scoliosis patients and their caregiver burden? A cross-sectional study in China.

BACKGROUND: Caregivers play a vital role in the recovery of scoliosis patients, but limited studies evaluate the caregivers' HRQoL and burden in health care. This study aimed to explore the health-related quality of life (HRQoL) of scoliosis patients and their caregivers, and identify the factors influencing caregiver burden in Eastern China. METHODS: This cross-sectional study was conducted from August 2018 to January 2019 at the Shandong Provincial Hospital, Jinan, China. The HRQoL of scoliosis patients was measured by the Scoliosis Research Society-22r (SRS-22r), five-level EQ-5D (EQ-5D-5L) and Child Health Utility 9D (CHU9D). The caregivers' questionnaires consist of the EQ-5D-5L, WHO-five wellbeing index (WHO-5), 22-item Zarit Caregiver Burden Interview (ZBI-22) and Social Support Rating Scale (SSRS). Spearman correlation coefficients were used to estimate the relationship among caregivers' burden, social support, HRQoL, and SWB. Cohen's effect size (Cohen's d) was used to assess the ZBI-22 total score between different groups. Multiple stepwise hierarchical linear regression models were conducted to assess the associated factors of caregiver burden. RESULTS: There were 59 scoliosis patients and their caregivers (n = 59) included in the analysis. The mean health state utility of adolescent scoliosis patients (n = 39) was 0.718 (95%CI: 0.654, 0.782) based on CHU9D and adult scoliosis patients (n = 20) was 0.663 (95%CI: 0.471, 0.855) based on EQ-5D-5L. The mean health state utility of male scoliosis patients (0.792/0.667) was higher than females (0.681/0.662) based on CHU9D and EQ-5D-5L (p > 0.05), respectively. The ZBI-22 total score of scoliosis patients' caregivers was 27.86 (SD: 20.59). Scoliosis patients' HRQoL was significantly inversely correlated with caregiver burden, and the HRQoL and subjective wellbeing (SWB) of caregivers were moderately and inversely correlated with caregiver burden. The regression results showed that the patients' age and caregivers' SWB were key characteristics associated with caregiver burden. CONCLUSIONS: The caregiver burden of adolescent patients was higher than that of adult patients, and the satisfaction rate of adolescent scoliosis patients was higher than that of adult scoliosis patients. Improving the functional state of scoliosis patients and providing appropriate nursing practice education from health professionals would be necessary to effectively improve caregivers SWB and alleviate caregiver burden.

Patient and clinician perspectives on shared decision-making in infertility treatment: A qualitative study.

OBJECTIVES: To explore the considerations and barriers to implementing shared decision-making (SDM) in infertility treatment among female infertility patients, their male spouses, and fertility clinicians. METHODS: Participants were recruited from a reproductive medicine hospital in China's Shandong Province using purposive sampling. One-on-one interviews were held with female infertility patients and their spouses. In addition, a focus group discussion was conducted with fertility clinicians. Data analysis was subjected to open, axial, and selective coding. RESULTS: Nineteen female infertility patients and 10 male spouses were interviewed one-on-one. Five clinicians participated in the focus group discussion. Most female patients wanted to participate in the decision-making process, and that spouses and fertility clinicians supported SDM. Furthermore, key barriers were identified from the perspectives of multiple stakeholders, including communication difficulties, psychological pressure on female patients, patient preferences, multiple treatment stages, male spousal participation, clinician-patient trust, and subjective patient factors. CONCLUSIONS/PRACTICE IMPLICATIONS: This study explored the considerations of and barriers to implementing SDM in infertility treatment. Key barriers were identified from the perspectives of multiple stakeholders. Based on the findings, clinicians should encourage patients and their spouses to actively participate in decision-making, and provide objective and realistic guidance.

Patient-reported outcomes in Gaucher's disease: a systematic review.

BACKGROUND: Gaucher's disease (GD), a rare condition, represents the most common lysosomal storage disorder. The cardinal manifestations of GD are fatigue, hepatosplenomegaly, anemia, thrombocytopenia, bone pain, and bone infarction, thereby culminating in a marked deterioration of patients' quality of life (QoL). Patient-reported outcomes (PROs) offer valuable insights into the impact of GD on patients' QoL and symptoms. This systematic review aimed to identify and analyze PROs and outcome measures in GD patients. METHODS: We systematically searched PubMed, Web of Science Core Collections, EMBASE, SCOPUS, Cochrane Library, PsycINFO, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM). The methodological quality of the included studies was assessed using a mixed methods assessment tool. RESULTS: A total of 33 studies were identified, encompassing 24 distinct patient-reported outcome instruments, with the most frequently employed instrument being the SF-36. The study designs included eighteen cross-sectional studies, seven pre- and post-intervention investigations, three randomized controlled trials, two cohort studies, two qualitative inquiries, and one validation study. These studies explored diverse domains such as the QoL and cardinal symptoms (e.g., fatigue, pain, bleeding, cognition, social relationships, and psychological functioning) in patients with GD. Furthermore, significant attention was directed towards the appraisal of the therapeutic benefits of various interventions in patients with GD. A novel GD-specific instrument has also been developed, which has two applied versions: a 24-item variant for routine clinical monitoring and a 17-item form for use in clinical trials. CONCLUSION: PROs have garnered increased attention and concern in the realm of GD. Despite this progress, it is noteworthy that the instruments used to measure PROs in GD are still predominantly generic instruments. While researchers have endeavored to develop and validate a disease-specific instrument, currently the use of this instrument is limited. Owing to several challenges, including the small number of patients, heterogeneity of the disease, and cross-regional discrepancies in study findings, GD poses substantial difficulties in the measurement of QoL and development of instruments. Consequently, patients with GD require more dependable measurement instruments that accurately reflect their QoL, efficacy of treatment, and facilitate healthcare decision-making.

Preoperative automatic reminder systems and impact on quality and compliance with colonoscopy preparation: A multicenter randomized controlled trial.

OBJECTIVES: Traditional preoperative reminding services have been applied to enhance the quality of bowel preparation for colonoscopy. In this study we aimed to evaluate the effectiveness of an automated electronic reminder system (E-reminder) on improving bowel preparation and the quality of preoperative education before colonoscopy. METHODS: From August 2021 to March 2022, 833 outpatients aged 50-75 years who underwent colonoscopy were included and randomly assigned to the E-reminder group and the control group. While the control group received routine preoperative education. The E-reminder group received automatic phone call, text message reminders and web services regarding the details of bowel preparation before the colonoscopic examination. The quality of bowel preparation was evaluated by the Boston Bowel Preparation Scale (BBPS) score and the previously validated objective evaluation scale of automatic BBPS (e-BBPS). RESULTS: In manual assessment, the rate of adequate bowel preparation was improved in the E-reminder group of intention-to-treat population using BBPS (60.7% vs 54.5%, P = 0.01). The percentage of objective evaluated adequate bowel preparation using e-BBPS in the E-reminder group of per-protocol population was significantly higher than that in the control group (76.9% vs 69.2%, P = 0.02). CONCLUSIONS: E-reminder was an effective tool to improve the quality of bowel preparation and compliance with medical instructions. It may be regarded as an efficient and convenient education tool, improving the quality of medical service.

Selective surface enhanced Raman detection and effective photocatalytic degradation of sulfonamides antibiotic based on a flexible three-dimensional chitosan/carbon nitride/silver substrate.

The prevalence of sulfonamide residues in aquatic environments poses serious environmental risks, and the sensitive detection and effective degradation of sulfonamides have attracted widespread attention. Here, the environmentally friendly chitosan (CS)/carbon nitride (CN) with three-dimensional porous structure is fabricated by freeze-drying method, and subsequently a new bifunctional flexible substrate (CS/CN/Ag) is prepared by anchoring of small sized AgNPs (6 ∼ 12 nm) on CS/CN. Importantly, the CS/CN/Ag substrate shows high adsorption capacity (∼ 83.06%) for sulfamethoxazole (SMX) solution within 20 mins and the limit of detection can be as low as 7.46 × 10-9 mol·L-1 with an enhancement factor of 3.3 × 105. Also, the CS/CN/Ag substrate displays highly selective for surface-enhanced Raman spectroscopy (SERS) detection of sulfonamides and also shows excellent SERS response for SMX in hospital wastewater samples. In addition, the photocatalytic degradation efficiency of SMX could reach as high as 99.22% within 20 mins of irradiation and the CS/CN/Ag still maintains outstanding photocatalytic performance after six cycles. Moreover, the Ag content in the CS/CN/Ag substrate is only 2.35%, and also the CS/CN/Ag exhibits good uniformity, repeatability, recyclability and stability. Therefore, this flexible and cost-effectively substrate of CS/CN/Ag shows great potential for the simultaneous SERS detection and photocatalytic degradation of pollutants in actual wastewater samples.

Influence of Mycorrhiza on C:N:P Stoichiometry in Senesced Leaves.

Senesced leaves play a vital role in nutrient cycles in the terrestrial ecosystem. The carbon (C), nitrogen (N) and phosphorus (P) stoichiometries in senesced leaves have been reported, which are influenced by biotic and abiotic factors, such as climate variables and plant functional groups. It is well known that mycorrhizal types are one of the most important functional characteristics of plants that affect leaf C:N:P stoichiometry. While green leaves' traits have been widely reported based on the different mycorrhiza types, the senesced leaves' C:N:P stoichiometries among mycorrhizal types are rarely investigated. Here, the patterns in senesced leaves' C:N:P stoichiometry among plants associated with arbuscular mycorrhizal (AM), ectomycorrhizal (ECM), or AM + ECM fungi were explored. Overall, the senesced leaves' C, with 446.8 mg/g in AM plants, was significantly lower than that in AM + ECM and ECM species, being 493.1 and 501.4 mg/g, respectively, which was mainly caused by boreal biomes. The 8.9 mg/g senesced leaves' N in ECM plants was significantly lower than in AM (10.4 mg/g) or AM + ECM taxa (10.9 mg/g). Meanwhile, the senesced leaves' P presented no difference in plant associations with AM, AM + ECM and ECM. The senesced leaves' C and N presented contrary trends with the changes in mean annual temperature (MAT) and mean annual precipitation (MAP) in ECM or AM + ECM plants. The differences in senesced leaves' C and N may be more easily influenced by the plant mycorrhizal types, but not P and stoichiometric ratios of C, N and P. Our results suggest that senesced leaves' C:N:P stoichiometries depend on mycorrhizal types, which supports the hypothesis that mycorrhizal type is linked to the evolution of carbon-nutrient cycle interactions in the ecosystem.

Preparation of fat replacer utilizing gluten and barley ß-glucan and the interaction between them.

BACKGROUND: Fat replacers prepared from polysaccharides and proteins possess functional properties of both polysaccharides and proteins. In this study, an aqueous system of barley ß-glucan (BBG) and gluten was prepared. The interactions between BBG and gluten (with/without extrusion modification) were studied. Triple analysis methods, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and low-field nuclear magnetic resonance (LF-NMR), were utilized to analyze the freezing-thawing and thermal evaporation process, as well as the distribution state of water. Meanwhile, fluorescence microscopic analysis, dynamic rheological analysis and electrophoresis analysis were used to study the structure and rheological properties of the system. RESULTS: The results showed that BBG significantly increased the water-holding capacity of gluten, regardless of extrusion treatment, with the water absorption reaching about 4.8 to 6.4 times of its weight, which was 1 to 2.5 times higher than that without BBG. The triple analysis results suggested that BBG increased the binding capacity of the system to weakly bound water, hindered the aggregation of gluten and reduced the thermal decomposition temperature of the BBG and gluten composite system. After the gluten was extruded and homogenized with the BBG solution, the appearance of the composite system was more uniform and delicate. CONCLUSIONS: In conclusion, BBG increased the water-holding capacity of the BBG and gluten composite system. With these changes, the composite system presented great potential for the preparation of polysaccharide-gluten fat replacer. © 2023 Society of Chemical Industry.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Robust and dynamic underwater adhesives enabled by catechol-functionalized poly(disulfides) network.

Developing molecular approaches to the creation of robust and water-resistant adhesive materials promotes a fundamental understanding of interfacial adhesion mechanisms as well as future applications of biomedical adhesive materials. Here, we present a simple and robust strategy that combines natural thioctic acid and mussel-inspired iron-catechol complexes to enable ultra-strong adhesive materials that can be used underwater and simultaneously exhibit unprecedentedly high adhesion strength on diverse surfaces. Our experimental results show that the robust crosslinking interaction of the iron-catechol complexes, as well as high-density hydrogen bonding, are responsible for the ultra-high interfacial adhesion strength. The embedding effect of the hydrophobic solvent-free network of poly(disulfides) further enhances the water-resistance. The dynamic covalent poly(disulfides) network also makes the resulting materials reconfigurable, thus enabling reusability via repeated heating and cooling. This molecule-engineering strategy offers a general and versatile solution to the design and construction of dynamic supramolecular adhesive materials.

Evaluating health-related quality of life and subjective wellbeing among infertility patients: a cross-sectional study in mainland China.

PURPOSE: This study aimed to explore the health-related quality of life (HRQoL) and subjective wellbeing (SWB) of infertility patients in mainland China and to investigate the relationships between HRQoL and SWB instruments in infertility patients. METHODS: We conducted this cross-sectional study in the Hospital for Reproductive Medicine Affiliated of Shandong University between April 2019 and November 2019. Participants self-completed the five-level EQ-5D (EQ-5D-5L) questionnaire, the Assessment of Quality of Life (AQoL)-8D, and the WHO-5 wellbeing index (WHO-5). The agreements between EQ-5D-5L and AQoL-8D were assessed employing intraclass correlation coefficient (ICC) and Bland-Altman plots. Exploratory factor analysis (EFA) was conducted to examine the difference in descriptive systems among the three instruments. RESULTS: We analyzed a valid sample of 618 infertility patients (84.4%). The mean scores of the total EQ-5D-5L, AQoL-8D, and WHO-5 were 0.96 (95%CI 0.96, 0.96), 0.80 (95%CI 0.79, 0.81), and 16.92 (95%CI 16.52, 17.31), respectively. Patients diagnosed with primary infertility had significantly lower HRQoL and SWB than those with secondary infertility. The ICC of EQ-5D-5L and AQoL-8D was 0.14. The AQoL-8D (r = 0.625) was more strongly correlated with WHO-5 than with the EQ-5D-5L (r = 0.262). The EFA results indicated that HRQoL instruments and the WHO-5 instruments were complementary rather than substitutable. CONCLUSIONS: Poorer HRQoL and SWB were found that primary than secondary infertility patients. There exists a poor agreement between EQ-5D-5L and AQoL-8D and the difference in the psychosocial components may explain the difference. Measuring both HRQoL and SWB could provide complementary information for infertility patients.

C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

A portable architectonics of Al/carbon nitride/metal-organic frameworks anchored Ag nanoparticles for SERS detection and photocatalytic degradation of fungicide.

In recent years, it is urgent to develop bi-functional materials for highly sensitive SERS detection and photocatalytic degradation of contaminants in water of fish pond. Herein, using 5-mercapto-1-methyltetrazole as the ligand, the tree-trunk like zeolitic imidazolate framework (ZIF-8) is induced and in-situ grown on the surface of aluminum/flower carbon nitride (Al/f-C3N4). Then, AgNPs are tightly anchored in ZIF-8 of Al/f-C3N4/ZIF-8 by strong Ag-N and Ag-S bonds, and a portable architecture of Al/f-C3N4/ZIF-8/Ag is successfully prepared. Results indicate that the Al/f-C3N4/ZIF-8/Ag architecture exhibits excellent SERS activity and the detection limit can as low as 2.15 × 10-11 mol⋅L-1 for crystal violet (CV, a typical fungicide). Also, the Al/f-C3N4/ZIF-8/Ag substrate presents good photocatalytic activity for CV molecule, and the degradation efficiency reaches 98.58% after illumination for 90 min. This is mainly due to the good adsorption capacity of ZIF-8 which can enrich more CV molecules and pull them to "hot spots" generated by Ag in Al/f-C3N4/ZIF-8/Ag, and thus SERS response are enhanced significantly. Besides, the strong synergistic effect of f-C3N4, ZIF-8 and AgNPs is also important which facilitates the separation of photogenerated electrons and holes. Thus, the designed portable and bi-functional substrate could be used as a potential material for the detection and removal of CV in practical application.