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Abstract Background The prevalence of invasive pulmonary aspergillosis (IPA) among patients with interstitial lung disease (ILD) is steadily increasing, leading to high mortality. The purpose of this study is to analyze the clinical features and risk factors of IPA in patients with ILD. Methods 353 hospitalized ILD patients admitted in Nanjing Drum Tower Hospital from March 2023 and April 2024 were enrolled. The enrolled patients were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. Results Among 353 patients with ILD, 58 who suffered from IPA were identified. Among them, 2 (3.4%) episodes of proven IPA and 56 (96.6%) of probable IPA were diagnosed. The median age was 68.4 ± 8.6 years, and 35 patients were men. The forms of ILD included idiopathic pulmonary fibrosis (n = 21), interstitial pneumonia with autoimmune features (n = 13), rheumatoid arthritis related interstitial pneumonia (n = 11) and Sjögren′s syndrome (n = 4). The clinical features of IPA in ILD were cough (100.0%), dyspnea (93.1%) and fever (55.2%). Chest CT images showed reticulation (87.9%), traction bronchiectasis (84.5%), GGO (77.6%), honeycombing (69.0%), consolidation (44.8%) and pleural effusion (24.1%). The incidence of honeycombing and consolidation were higher in ILD patients with IPA compared to control group (P

Abstract The purpose of this study was to investigate the effects of different electrical stimulation methods (bilateral electroacupuncture (BEA), unilateral EA (UEA), transcutaneous electrical acustimulation (TEA, stimulation via surface electrodes placed at acupoints), and sacral nerve stimulation (SNS)) on visceral pain in a rodent model of irritable bowel syndrome (IBS). Ten-day-old male and female pups were treated with 0.2 ml of 0.5% acetic acid (AA) solution. Visceral sensitivity was assessed using an electromyogram (EMG) in response to graded colorectal distension. In the first experiment, bilateral EA at ST36 acupoint was performed with different parameters in male rats to determine the best stimulation parameters. In the second experiment, male rats were randomly assigned into the Sham, BEA, UEA, TEA, and SNS groups to determine the best stimulation method. Lastly, the AA-treated female rats were randomly assigned into the BEA and sham groups to investigate a potential treatment difference between the sexes. Two distinct sets of stimulation parameters were used: Set 1 (100 Hz, 0.5 ms pulse width, 0.1 s ON, 0.4 s OFF, 0.4–3.0 mA current) and Set 2 (25 Hz, 0.5 ms pulse width, 2 s ON, 3 s OFF, 0.4–3.0 mA current). Results (1) The parameter set of 100Hz was found to be most effective in reducing visceral pain. (2) Both acute UEA and TEA effectively relieved visceral pain, whereas acute SNS did not exhibit such an effect. (3) Acute BEA improved visceral pain in both male and female rats. Conclusions These findings suggest that transcutaneous ST36 stimulation is as effective as direct ST36 stimulation and unilateral ST36 stimulation is comparable to bilateral stimulation. Development of a novel therapy using unilateral transcutaneous ST36 stimulation is warranted.

Abstract Background Adenotonsillar hypertrophy (ATH) is a major cause of pediatric obstructive sleep apnea (OSA), potentially impacting craniofacial growth and development. Currently, whether children with ATH exhibit distinctive hyoid bone position and upper airway morphology remains uncertain. This research aimed to compare the hyoid bone position and upper airway morphology of children with and without ATH. Methods A total of 199 children aged 6–8 years were recruited for the study, and their pre-treatment lateral cephalograms were obtained. The size of the adenoids and tonsils on the lateral cephalogram was assessed based on Fujioka’s and Baroni’s methods for classification into groups: adenoid hypertrophy only (AHO) group, tonsillar hypertrophy only (THO) group, adenoid and tonsillar hypertrophy (AH + TH) group, and control group (CG). The position of the hyoid bone and upper airway morphology was analyzed using Dolphin Image Software. Results The distance between the hyoid bone and mentum was greater in the THO group compared to the AHO group (P = 0.005). Children in the AHO group exhibited a longer soft palate (SPL) compared to the THO group (P = 0.014), whereas the THO group displayed a reduced SPL in comparison to healthy controls (P = 0.008). The THO group showed a more inferior tongue position compared to children in the AHO group (P = 0.004). Subjects in the THO group exhibited significantly wider inferior airway space compared to healthy children (P

Abstract Background Pitt–Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder that results from variants of TCF4 gene. PTHS follows an autosomal dominant inheritance pattern and the underlying pathological mechanisms of this disease are still unclear. Methods Whole-genome sequencing (WGS) was conducted to screen for potential pathogenic variant in a boy highly suspected of having a genetic disorder. PCR and Sanger sequencing were used to verify the effects of the variant. Serum TCF4 levels were measured by ELISA. Results We present a 4-year and 3-month-old Chinese boy clinically and molecularly diagnosed with PTHS. The proband experienced global development delay, and the preliminary clinical diagnosis was cerebral palsy. WGS identified a de novo heterozygous variant: c.*1A > G in the 3’UTR of the TCF4 gene as a potential cause of his condition. The variant was verified to cause aberrant mRNA splicing by PCR and the aberrant splicing was confirmed by Sanger sequencing. Conclusion The study identified and demonstrated the pathogenicity of a novel 3’UTR site TCF4 variant for the first time. This research enhances understanding of pathogenetic mechanisms of PTHS and aids genetic counseling and diagnosis.

Objective To investigate the effect of different antibacterial agents combined with tigecycline in patients with multidrug-resistant Acinetobacter baumannii (MDRAB)-related ventilator-associated pneumonia (VAP), and to provide options for better treatment of the disease in clinical practice. Methods A retrospective analysis was performed for the clinical data of the patients with MDRAB-related VAP who were admitted from January 2016 to August 2023 in Qingdao municipal Hospital, and according to the treatment regimen, they were divided into tigecycline group (group A) with 56 patients, cefoperazone-sulbactam combination therapy group (B group) with 42 patients, and carbapenem combination therapy group (group C) with 24 patients. The three groups were compared in terms of infection and related outcome measures. Results There were no significant diffe-rences in the type of pathogene infected and infection sites between the three groups (P>0.05). Groups B and C had a significantly higher bacterial clearance rate than group A (χ2=5.38,4.48,P0.05). Conclusion Tigecycline combined with cefoperazone-sulbactam or carbapenem achieves a higher bacterial clearance rate than tigecycline alone in MDRAB-related VAP, and combined medication is a relatively good treatment option.

This study investigated the effectiveness of visual training or verbal training on how to use a text-picture processing strategy for learning from computer-based multimedia instructional material. Sixty-nine university students were randomly assigned to the verbal training group (students received text-based instruction for a text-picture processing strategy), the visual training group (students observed a video depicting an expert's eye fixations while using a text-picture processing strategy for an initial portion of a multimedia lesson) or the control group (students did not receive any instruction). During reading a multimedia lesson on biology, students' eye movements were tracked; and after the lesson, students took a posttest. Concerning learning outcomes, both visual and verbal training helped students perform better than the control group on a recall test and the verbal training group perform better on a transfer test. Concerning learning processes, both visual and verbal training caused students to attend less to on-screen text and more to on-screen pictures as compared to the control group. Mediation analysis showed that increased attention to pictures was a mediator for better learning outcomes. Practical and theoretical implications are discussed.

Abstract This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.

Abstract Background Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. In vitro expansion is necessary to provide clinical-grade quantities of mesenchymal stem cells; however, it has been reported to cause replicative senescence and undefined dysfunction in mesenchymal stem cells. Quality control assessments of in vitro expansion have rarely been addressed in ongoing trials. Young small extracellular vesicles from the remnant pulp of human exfoliated deciduous teeth stem cells have demonstrated therapeutic potential for diverse diseases. However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines. Results We demonstrated that mitochondrial structural disruption precedes cellular dysfunction during bone marrow-derived mesenchymal stem cell replication, indicating mitochondrial parameters as quality assessment indicators of mesenchymal stem cells. Dynamin-related protein 1-mediated mitochondrial dynamism is an upstream regulator of replicative senescence-induced dysfunction in bone marrow-derived mesenchymal stem cells. We observed that the application of young small extracellular vesicles could rescue the pluripotency dissolution, immunoregulatory capacities, and therapeutic effects of replicative senescent bone marrow-derived mesenchymal stem cells. Mechanistically, young small extracellular vesicles could promote Dynamin-related protein 1 translocation from the cytoplasm to the mitochondria and remodel mitochondrial disruption during replication history. Conclusions Our findings show that Dynamin-related protein 1-mediated mitochondrial disruption is associated with the replication history of bone marrow-derived mesenchymal stem cells. Young small extracellular vesicles from human exfoliated deciduous teeth stem cells alleviate replicative senescence by promoting Dynamin-related protein 1 translocation onto the mitochondria, providing evidence for a potential rejuvenation strategy. Graphical Abstract

Abstract Background This study aims to construct a clinical prediction model and create a visual line chart depicting the risk of acute kidney injury (AKI) following resuscitation in cardiac arrest (CA) patients. Additionally, the study aims to validate the clinical predictive accuracy of the developed model. Methods Data were retrieved from the Dryad database, and publicly shared data were downloaded. This retrospective cohort study included 347 successfully resuscitated patients post-cardiac arrest from the Dryad database. Demographic and clinical data of patients in the database, along with their renal function during hospitalization, were included. Through data analysis, the study aimed to explore the relevant influencing factors of acute kidney injury (AKI) in patients after cardiopulmonary resuscitation. The study constructed a line chart prediction model using multivariate logistic regression analysis with post-resuscitation shock status (Post-resuscitation shock refers to the condition where, following successful cardiopulmonary resuscitation after cardiac arrest, some patients develop cardiogenic shock.), C reactive protein (CRP), Lactate dehydrogenase (LDH), and Alkaline phosphatase (ALP) identified as predictive factors. The predictive efficiency of the fitted model was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results Multivariate logistic regression analysis showed that post-resuscitation shock status, CRP, LDH, and PAL were the influencing factors of AKI after resuscitation in CA patients. The calibration curve test indicated that the prediction model was well-calibrated, and the results of the Decision Curve Analysis (DCA) demonstrated the clinical utility of the model constructed in this study. Conclusion Post-resuscitation shock status, CRP, LDH, and ALPare the influencing factors for AKI after resuscitation in CA patients. The clinical prediction model constructed based on the above indicators has good clinical discriminability and practicality.

This work elucidates the interactions between Re and hydrogen at γ/γ′ interfaces, enhancing the hydrogen-embrittlement resistance of nickel-based single-crystal superalloy (Ni-SX). The H-charged Ni-SX exhibits severe embrittlement characterized by the appearance of parallel dislocation slip bands and micro-cracks, which could be effectively mitigated through improving the Re content. The segregation behaviors of hydrogen at γ/γ′ interfaces, as captured by hydrogen microprint technique, significantly diminish interfacial cohesion strength by reducing the local atomic bonding strength. Detailed characterizations of bonding charge density highlight that Re plays a crucial role in reducing hydrogen embrittlement susceptibility by suppressing the hydrogen-induced degradation of bonding strength.

Abstract Objective To explore the correlation between serum bilirubin, blood uric acid, and C-reactive protein (CRP) and the severity of chronic obstructive pulmonary disease (COPD). Methods: Patients with COPD who were admitted to our hospital between March 2020 and March 2023 were retrospectively studied. Based on whether their condition progressed to the acute exacerbation stage, they were divided into an exacerbation group (100 cases) and a stability group (100 cases). The clinical data from both groups were analysed to assess the correlations between serum bilirubin, blood uric acid, CRP, and the severity of COPD. Results: Univariate analysis indicated significant differences in the neutrophil-to-lymphocyte ratio (t = 5.678, P

Gene fusions offer new therapeutic options for patients with metastatic colon cancer (CC). BRAF gene fusions are infrequent somatic mutations found in CC with prognostic and promising targeted therapies. CC diagnosed before the age of 50 was regarded as early-onset CC (EOCC). The incidence of EOCC is increasing, yet there is a clear unmet need to improve the management of EOCC. Herein, we selectively reported a case of metastatic EOCC with rare BRAF gene fusions. The right-sided tumors were radically resected. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded tissues to eliminate gene variations. Histologically, the colonic hepatic flexure showed focal mucinous adenocarcinoma changes along with high-grade intraepithelial neoplasia. The results of histopathological examination belonged to pT1bN1bM0 ⅢA stage. Targeted DNA sequencing revealed AGAP3::BRAF (A10;B9) fusion and BRAF::AGAP3 (B8;A11) fusion were simultaneously detected in this case. Microsatellite instability-high (MSI-H) and RAS/BRAF V600E mutations were not detected. During a limited 1.5-year follow-up period, neither a confirmed local recurrence nor a distant organ metastasis occurred in this case. We propose that BRAF fusion variations can occur in metastatic EOCC.

Infections caused by Acinetobacter baumannii (A. baumannii) have emerged as a global public health concern because of high pathogenicity of this bacterium. Monoclonal antibodies (mAbs) have a lower likelihood of promoting drug resistance and offer targeted treatment, thereby reducing potential adverse effects; however, the therapeutic potential of mAbs targeting A. baumannii has not been fully characterized. In this study, mAbs against the outer membrane proteins (OMPs) of A. baumannii were isolated in a high-throughput manner. The ability of Omp38-specific mAbs to bind to A. baumannii strains from diverse sources was confirmed via enzyme-linked immunosorbent assay (ELISA). Intravenous administration of the Omp38-specific mAbs significantly improved the survival rate and reduced the bacterial load in a mouse model of lethal A. baumannii infection. Flow cytometry and ELISA confirmed that immune cell infiltration and cytokine production, respectively, decreased in a mouse model of sublethal A. baumannii infection. In addition, analysis of the Omp38-mAb C3 binding conformation revealed the potential mechanism of broad-spectrum binding activity of this mAb against A. baumannii. Taken together, these findings indicate that mAbs against Omp38 facilitate bacterial clearance from host, minimize inflammatory mediator release and reduce host damage, highlighting the potential of Omp38-specific mAbs in the clinical treatment of A. baumannii infection.

Impervious surfaces are important indicators of human activity, and finding ways to quantify the gain and loss of impervious surfaces is important for sustainable urban development. However, most relevant studies assume that the transformation of natural surfaces to impervious surfaces is irreversible; thus, the losses of impervious surfaces are often ignored. Here, we propose a novel framework taking advantage of continuous change detection, multitemporal classification, and LandTrendr optimization to track the annual gains and losses in impervious surfaces. It may be the first study to focus on both loss and gain of impervious surfaces using time-series Landsat imagery. Specifically, we built dual continuous-change-detection models to pursue lower commission and omission errors for generating time-series training samples. Then, we adopted time-series classifications from multisource information and derived training samples to develop annual impervious-surface maps from 1985 to 2022 in Beijing. Afterwards, a novel optimization algorithm considering spatial heterogeneity and taking advantage of the LandTrendr algorithm was also proposed to optimize the spatiotemporal consistency of these impervious-surface maps. We further calculated accuracy metrics for the proposed method using time-series validation points, finding overall accuracies of 92.91 %±0.97 % and 93.17 %±1.26 % for gains and losses in impervious surfaces, respectively, using a one-year tolerance. Lastly, we revealed the gains and losses of impervious surfaces in Beijing during 1985–2022. The gained area of impervious surfaces was found to be 1996.21 km2 ± 18.58 km2, and there was a rapid increase during 2000–2010; the total lost area of impervious surfaces was 898.60 km2 ± 4.58 km2, of which 564.85 km2 ± 2.21 km2 first increased and was then lost. Therefore, the proposed method provides a new way of tracking the gain and loss of impervious surfaces, and it offers new possibilities for monitoring urban regreening.

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1β) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.

This study introduces HairDB, an online database serving as a comprehensive repository of hair-related chemicals for exposome research. HairDB was created via an integrative approach. It first extracted 4,184 unique hair-related chemicals through text mining of over 34 million PubMed abstracts and 5.2 million PubMed Central articles, followed by manual data checking. HairDB also applied an artificial intelligence-enabled search to discover organic aerosol biomarkers in literature. A set of 768 chemicals used in hair-related products was then curated through a combination of manual searches and data extraction from the Cosmetic Ingredient Database (CosIng) of the European Union. From manually reading review papers, 29 organic aerosol biomarkers were extracted. Furthermore, 3,679 known exposure chemicals extracted from the Toxin and Toxin Target Database (T3DB) were incorporated in HairDB to represent the possible environmental exposures detected on hair surfaces. The comprehensive set of chemicals captured in HairDB represents the current knowledge of what can be found in and on hair. HairDB was constructed as a user-friendly web interface, allowing easy exploration of hair-related chemicals and tailored for annotating mass spectrometry-based hair exposomics data. The development of HairDB marks an important step forward in using hair as a biological matrix for chemical exposure measurement, facilitating the adoption of hair for exposome research. HairDB is publicly available at https://www.hairdb.ca/.

Overnutrition triggers obesity and metabolic dysregulation, causing metaflammation. D-allulose, exhibits anti-obesity and hypoglycemic benefits. However, its involvement in metaflammation remains incompletely understood. In this study, high-fat diet-fed mice were supplemented with 300 mg/kg of D-allulose for 60 days. Levels of inflammation in various tissues, changes in intestinal barrier function, and gut microbiota composition, which serve as key markers of metaflammation, were analyzed. We foud that D-allulose significantly attenuated HFD-induced metaflammation, evidenced by a reduction in inflammation levels and in the activation of proinflammatory macrophages in adipose tissue. Additionally, D-allulose effectively restored impaired intestinal barrier function in HFD-fed mice by enhancing the expression of tight junction proteins, replenishing goblet cell populations, and modulating intestinal flora composition, which improved intestinal barrier integrity and contributed to the attenuation of metaflammation. Our findings highlight the potential of D-allulose in obesity and metaflammation management and provide new directions for future applications and advancements of D-allulose.

Solid-state electrolytes have been demonstrated immense potential with their high density and safety for Li, Na batteries. The discovery of novel crystals is of fundamental scientific and technological interest in solid-state chemistry. The discovery, synthesis and application of energetically favourable solid-state electrolytes has been bottlenecked by expensive trial-and-error approaches. Machine learning has brought breakthroughs to solid-state electrolytes. Numerous solid-state electrolyte candidates have been screened by different models at multiscale, i.e., interatomic potentials, molecular dynamics, ionic conductivity. Machine learning method also accelerate the synthesis prediction, mechanism discovery and interface design. This review would answer the question what can be done for solid-state electrolytes by machine learning, including descriptor, model, algorithm etc. This paper will promote fast integration between scientists in materials, software, computing discipline.

Objective To investigate the effect of STX5 on the metastasis of hepatocellular carcinoma (HCC) and its mechanism. Methods Clinical data were collected from 36 patients who were diagnosed with HCC in our hospital from January to December 2015, and the correlation between the expression level of STX5 in tumor tissue and the clinicopathological features of HCC patients was analyzed. Human hepatoma cells MHCC97H were divided into groups A and B and were transfected with negative control plasmid and STX5 overexpression plasmid, respectively. Human hepatoma cells Huh7 were divided into groups C and D and were transfected with negative control lentivirus and STX5 knockdown virus, respectively. Western blot was used to measure the protein expression level of STX5 in groups A, B, C, and D, wound healing was used to measure the migration ability of cells in groups A, B, C, and D, and Transwell assay was used to measure the migration ability of cells in groups A, B, C, and D. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed for the differentially expressed genes in groups A and B obtained by transcriptomic sequencing, and RT-qPCR was used to measure the levels of the most significantly differentially expressed genes in group A and B. MHCC97H cells were divided into groups E, F, G, and H and were transfected with negative control plasmid, STX5 overexpression plasmid, negative control plasmid+Sarilumab, and STX5 overexpression plasmid+Sarilumab, respectively. Scratch assay was used to measure the migration ability of cells in groups E, F, G, and H, and Transwell assay was used to measure the migration ability of cells in groups E, F, G, and H. Results The expression level of STX5 in tumor tissue was associated body mass index, presence or absence of hepatitis B virus infection, and the number of tumors (P

Abstract Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10–30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management. Graphical Abstract

Abstract Background Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic areas and the most common type of exudative pleural effusion in China. In clinical practice, distinguishing TPE from pleural effusion caused by other reasons remains a relatively challenging issue. The objective of present study was to explore the clinical significance of the pleural fluid lactate dehydrogenase/adenosine deaminase ratio (pfLDH/pfADA) in the diagnosis of TPE. Methods The clinical data of 618 patients with pleural effusion were retrospectively collected, and the patients were divided into 3 groups: the TPE group (412 patients), the parapneumonic pleural effusion (PPE) group (106 patients), and the malignant pleural effusion (MPE) group (100 patients). The differences in the ratios of pleural effusion-related and serology-related indicators were compared among the three groups, and receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the parameter ratios of different indicators for the diagnosis of TPE. Results The median serum ADA level was higher in the TPE group (13 U/L) than in the PPE group (10 U/L, P

IntroductionWhile lymph node metastasis (LNM) plays a critical role in determining treatment options for endometrial cancer (EC) patients, the existing preoperative methods for evaluating the lymph node state are not always satisfactory. This study aimed to develop and validate a nomogram based on intra- and peritumoral radiomics features and multiparameter magnetic resonance imaging (MRI) features to preoperatively predict LNM in EC patients.MethodsThree hundred and seventy-four women with histologically confirmed EC were divided into training (n = 220), test (n = 94), and independent validation (n = 60) cohorts. Radiomic features were extracted from intra- and peritumoral regions via axial T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) mapping. A radiomics model (annotated as the Radscore) was established using the selected features from different regions. The clinical parameters were statistically analyzed. A nomogram was developed by combining the Radscore and the most predictive clinical parameters. Decision curve analysis (DCA) and the net reclassification index (NRI) were used to assess the clinical benefit of using the nomogram.ResultsNine radiomics features were ultimately selected from the intra- and peritumoral regions via ADC mapping and T2WI. The nomogram combining the Radscore, serum CA125 level, and tumor area ratio achieved the highest AUCs in the training, test and independent validation sets (nomogram vs. Radscore vs. clinical model: 0.878 vs. 0.850 vs. 0.674 (training), 0.877 vs. 0.838 vs. 0.668 (test), and 0.864 vs. 0.836 vs. 0.618 (independent validation)). The DCA and NRI results revealed the nomogram had greater diagnostic performance and net clinical benefits than the Radscore alone.ConclusionThe combined intra- and peritumoral region multiparameter MRI radiomics nomogram showed good diagnostic performance and could be used to preoperatively predict LNM in patients with EC.

The discrete element method (DEM) is commonly used for simulating particle systems at the engineering scale, but computational efficiency remains a limiting factor for large-scale particle system simulations. Existing coarse-grained methods have limited applicability and lack a universal theoretical basis. To address this issue, this study utilizes dimensional analysis to describe the scaling laws of physical quantities in an exact scaled system. By using representative volume elements (RVE), approximate conservation relationships for mass, momentum, and energy are established between the coarse-grained system and the original system. Scaling relationships for corresponding physical quantities at two different scales (global and particle level) are obtained.To validate the correctness of the proposed two-scale coarse-grained DEM method, the method is applied to the falling and rotation tests of bulk coal. The particle size in the actual tests is 4mm, while in the simulations, five groups of coal particles with different scaling coefficients ranging from 4 mm to 12 mm are used. The total volume of bulk coal in both the tests and simulations is 0.001 m3. The falling test of bulk coal uses the average impact force and the reposeangle as comparative indicators. The results show that as the particle size of coal increases, the relative errors of both indicators generally increase (at a particle size of 12 mm, the error in impact force is 14.36%, and the error in the reposeangle is 19.05%).The rotational test of bulk coal uses the correlation coefficient between the applied force on the upper sample and the profile curve of the bulk coal heap as a comparative indicator. The results show that as the particle size increases, the relative error increases, and the correlation coefficient generally decreases (at a particle size of 12 mm, the force error is 39.29%, and the correlation coefficient is 0.9574).The simulations require less time compared to the predicted duration, fully demonstrating the effectiveness of the dual-scale coarse-graining DEM method. The coarse-grained system can significantly improve computational efficiency within an acceptable range of errors.

Abstract Wetlands play a key role in maintaining ecological balance and climate regulation. However, due to the complex and variable spectral characteristics of wetlands, there are no publicly available global 30-meter time-series wetland dynamic datasets at present. In this study, we present novel global 30 m annual wetland maps (GWL_FCS30D) using time-series Landsat imagery on the Google Earth Engine platform, covering the period of 2000–2022 and containing eight wetland subcategories. Specifically, we make full use of our prior globally distributed wetland training sample pool, and adopt the local adaptive classification and spatiotemporal consistency checking algorithm to generate annual wetland maps. The GWL_FCS30D maps were found to achieve an overall accuracy and Kappa coefficient of 86.95 ± 0.44% and 0.822, respectively, in 2020, and show great temporal variability in the United States and the European Union. We expect the dataset would provide vital support for wetland ecosystems protection and sustainable development.

Abstract Background Breast cancer stem cell (CSC) expansion results in tumor progression and chemoresistance; however, the modulation of CSC pluripotency remains unexplored. Transmembrane protein 120B (TMEM120B) is a newly discovered protein expressed in human tissues, especially in malignant tissues; however, its role in CSC expansion has not been studied. This study aimed to determine the role of TMEM120B in transcriptional coactivator with PDZ-binding motif (TAZ)-mediated CSC expansion and chemotherapy resistance. Methods Both bioinformatics analysis and immunohistochemistry assays were performed to examine expression patterns of TMEM120B in lung, breast, gastric, colon, and ovarian cancers. Clinicopathological factors and overall survival were also evaluated. Next, colony formation assay, MTT assay, EdU assay, transwell assay, wound healing assay, flow cytometric analysis, sphere formation assay, western blotting analysis, mouse xenograft model analysis, RNA-sequencing assay, immunofluorescence assay, and reverse transcriptase-polymerase chain reaction were performed to investigate the effect of TMEM120B interaction on proliferation, invasion, stemness, chemotherapy sensitivity, and integrin/FAK/TAZ/mTOR activation. Further, liquid chromatography–tandem mass spectrometry analysis, GST pull-down assay, and immunoprecipitation assays were performed to evaluate the interactions between TMEM120B, myosin heavy chain 9 (MYH9), and CUL9. Results TMEM120B expression was elevated in lung, breast, gastric, colon, and ovarian cancers. TMEM120B expression positively correlated with advanced TNM stage, lymph node metastasis, and poor prognosis. Overexpression of TMEM120B promoted breast cancer cell proliferation, invasion, and stemness by activating TAZ-mTOR signaling. TMEM120B directly bound to the coil-coil domain of MYH9, which accelerated the assembly of focal adhesions (FAs) and facilitated the translocation of TAZ. Furthermore, TMEM120B stabilized MYH9 by preventing its degradation by CUL9 in a ubiquitin-dependent manner. Overexpression of TMEM120B enhanced resistance to docetaxel and doxorubicin. Conversely, overexpression of TMEM120B-∆CCD delayed the formation of FAs, suppressed TAZ-mTOR signaling, and abrogated chemotherapy resistance. TMEM120B expression was elevated in breast cancer patients with poor treatment outcomes (Miller/Payne grades 1–2) than in those with better outcomes (Miller/Payne grades 3–5). Conclusions Our study reveals that TMEM120B bound to and stabilized MYH9 by preventing its degradation. This interaction activated the β1-integrin/FAK-TAZ-mTOR signaling axis, maintaining stemness and accelerating chemotherapy resistance.

Abstract Background Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder that remains underdiagnosed and its clinical presentations and mutation profiles in a diverse population are yet to be evaluated. This retrospective study aims to investigate the clinical and genetic characteristics of Chinese patients with PTHS. Methods The clinical, biochemical, genetic, therapeutic, and follow-up data of 47 pediatric patients diagnosed with PTHS between 2018 and 2021 were retrospectively analyzed. Results The Chinese PTHS patients presented with specific facial features and exhibited global developmental delay of wide severity range. The locus heterogeneity of the TCF4 gene in the patients was highlighted, emphasizing the significance of genetic studies for accurate diagnosis, albeit no significant correlations between genotype and phenotype were observed in this cohort. The study also reports the outcomes of patients who underwent therapeutic interventions, such as ketogenic diets and biomedical interventions. Conclusions The findings of this retrospective analysis expand the phenotypic and molecular spectra of PTHS patients. The study underscores the need for a long-term prospective follow-up study to assess potential therapeutic interventions.

Abstract Targeting C5aR1 modulates the function of infiltrated immune cells including tumor-associated macrophages (TAMs). The gut microbiome plays a pivotal role in colorectal cancer (CRC) tumorigenesis and development through TAM education. However, whether and how the gut flora is involved in C5aR1 inhibition-mediated TAMs remains unclear. Therefore, in this study, genetic deletion of C5ar1 or pharmacological inhibition of C5aR1 with anti-C5aR1 Ab or PMX-53 in the presence or absence of deletion Abs were utilized to verify if and how C5aR1 inhibition regulated TAMs polarization via affecting gut microbiota composition. We found that the therapeutic effects of C5aR1 inhibition on CRC benefited from programming of TAMs toward M1 polarization via driving AKT2-mediated 6-phosphofructokinase muscle type (PFKM) stabilization in a TLR5-dependent manner. Of note, in the further study, we found that C5aR1 inhibition elevated the concentration of serum IL-22 and the mRNA levels of its downstream target genes encoded antimicrobial peptides (AMPs), leading to gut microbiota modulation and flagellin releasement, which contributed to M1 polarization. Our data revealed that high levels of C5aR1 in TAMs predicted poor prognosis. In summary, our study suggested that C5aR1 inhibition reduced CRC growth via resetting M1 by AKT2 activation-mediated PFKM stabilization in a TLR5-dependent manner, which relied on IL-22-regulated gut flora.

Abstract Background Potato late blight, caused by Phytophthora infestans, is the most devastating disease on potato. Dissecting critical immune components in potato will be supportive for engineering P. infestans resistance. Upon pathogens attack, plant Ca2+ signature is generated and decoded by an array of Ca2+ sensors, among which calcineurin B-like proteins (CBLs) coupled with plant specific CBL-interacting protein kinases (CIPKs) are much less explored in plant immunity. Results In this study, we identified that two differential potato CBL-CIPK modules regulate plant defense responses against Phytophthora and ROS production, respectively. By deploying virus-induced gene silencing (VIGS) system-based pathogen inoculation assays, StCBL3 was shown to negatively regulate Phytophthora resistance. Consistently, StCBL3 was further found to negatively regulate PTI and ETI responses in Nicotiana benthamiana. Furthermore, StCIPK7 was identified to act together with StCBL3 to negatively regulate Phytophthora resistance. StCIPK7 physically interacts with StCBL3 and phosphorylates StCBL3 in a Ca2+-dependent manner. StCBL3 promotes StCIPK7 kinase activity. On the other hand, another StCBL3-interacting kinase StCIPK24 negatively modulating flg22-triggered accumulation of reactive oxygen species (ROS) by interacting with StRBOHB. Conclusions Together, these findings demonstrate that the StCBL3-StCIPK7 complex negatively modulates Phytophthora resistance and StCBL3-StCIPK24 complex negatively regulate ROS production. Our results offer new insights into the roles of potato CBL-CIPK in plant immunity and provide valuable gene resources to engineer the disease resistance potato in the future.

Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells.

Abstract Noncontact humidity sensor overcomes the limitations of its contact sensing counterparts, including mechanical wear and cross infection, which becomes a promising candidate in healthcare and human-machine interface application. However, current humidity sensors still suffer the ubiquitous issue of uncomfortable wear and skin irritation hindering the long-term use. In this study, we report a skin-conformal and breathable humidity sensor assembled by anchoring MXenes-based composite into electrospun elastomer nanofibers coated with a patterned electrode. This composite is highly sensitive to the water molecules due to its large specific surface area and abundant water-absorbing hydroxyl groups, while the elastomeric nanofibers provide an ultrathin, highly flexible, and permeable substrate to support the functional materials and electrodes. This sensor presents not only excellent air permeability (0.078 g cm−2 d−1), high sensitivity (S = 704), and fast response/recovery (0.9 s/0.9 s), but also high skin conformability and biocompatibility. Furthermore, this humidity sensor is confirmed to realize the recognition of motional states and emotional modes, which provides a way for the advanced noncontact human-machine interface.

PLATZ is a novel zinc finger DNA-binding protein that plays an important role in regulating plant growth and development and resisting abiotic stress. However, there has been very little research on the function of this family gene in tomatoes, which limits its application in germplasm resource improvement. Therefore, the PLATZ gene family was identified and analyzed in tomato, and its roles were predicted and verified to provide a basis for in-depth research on SlPLATZ gene function. In this study, the PLATZ family members of tomato were identified in the whole genome, and 19 SlPLATZ genes were obtained. Functional prediction was conducted based on gene and promoter structure analysis and RNA-seq-based expression pattern analysis. SlPLATZ genes that responded significantly under different abiotic stresses or were significantly differentially expressed among multiple tissues were screened as functional gene resources. SlPLATZ17 was selected for functional verification by experiment-based analysis. The results showed that the downregulation of SlPLATZ17 gene expression reduced the drought and salt tolerance of tomato plants. Tomato plants overexpressing SlPLATZ17 had larger flower sizes and long, thin petals, adjacent petals were not connected at the base, and the stamen circumference was smaller. This study contributes to understanding the functions of the SlPLATZ family in tomato and provides a reference for functional gene screening.

Abstract Background Gexia-Zhuyu Tang (GZT), a traditional Chinese medicine formula, is used to treat a variety of diseases. However, its roles in gastric cancer (GC) remain unclear. Objective The aim of this study was to explore the roles and underlying molecular mechanisms of modified GZT in GC. Methods The effects of modified GZT on GC were investigated by constructing mouse xenograft models with MFC cell line. The fecal samples from low-dose, high-dose, and without modified GZT treatment groups were collected for the 16S rRNA gene sequencing and fecal microbiota transplantation (FMT). Histopathological alterations of mice were evaluated using the hematoxylin–eosin (HE). Immunohistochemical (IHC) analysis with Ki67 and GSDMD was performed to measure tissue cell proliferation and pyroptosis, respectively. Proteins associated with pyroptosis, invasion, and metastasis were detected by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to assess inflammation-related factors levels. Results Modified GZT inhibited GC tumor growth and reduced metastasis and invasion-related proteins expression levels, including CD147, VEGF, and MMP-9. Furthermore, it notably promoted caspase-1-dependent pyroptosis, as evidenced by a dose-dependent increase in TNF-α, IL-1β, IL-18, and LDH levels, along with elevated protein expression of NLRP3, ASC, and caspase-1. Additionally, modified GZT increased species abundance and diversity of the intestinal flora. FMT assay identified that modified GZT inhibited GC tumor progression through regulation of intestinal flora. Conclusions Modified GZT treatment may promote pyroptosis by modulating gut microbiota in GC. This study identifies a new potential approach for the GC clinical treatment.

Bacterial wilt triggered by the soil-borne pathogenic bacterium Ralstonia solanacearum is one of the most serious diseases in tomato plants, leading to huge economic losses worldwide. Biological control is considered an environmentally friendly and sustainable way to manage soil-borne diseases. In this study, Streptomyces sp. STD57 isolated from the rhizosphere of Adenophora stricta showed strong antibacterial activity against R. solanacearum. Pot experiments showed that strain STD57 exhibited a significant biocontrol effect (81.7%) on tomato bacterial wilt in the greenhouse environment. Furthermore, strain STD57 could inhibit the growth of weeds (Amaranthus retroflexus, Portulaca oleracea, and Echinochloa crusgalli) but promote the growth of crops (wheat, rice, and tomato). The plant growth-promoting substance was identified as indoleacetic acid (IAA) by high-pressure liquid chromatography–mass spectrometry and genome analysis. Coarse separation of the fermented extracts revealed that the antibacterial and herbicidal substances were mainly in the fermentation supernatant and belonged to different products. These findings suggested that strain STD57 may be a potential biocontrol and bioherbicide agent useful in agriculture.

Introduction Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy.Methods and analysis This is a two-arm, parallel-group, superiority cluster randomised controlled trial, with four clinics randomly assigned to the surgery-first arm and the orthodontic-first arm in a 1:1 ratio. The Alt-RAMEC protocol involves alternate activation and deactivation of the expander’s jet screw over 6 weeks to stimulate maxillary suture distraction. Patients will be instructed to wear the PFM for a minimum of 14 hours per day. The primary outcomes are changes in Wits appraisal and the degree of maxillary advancement from baseline to the end of orthodontic treatment. Lateral cephalometric radiographs, polysomnography, Obstructive Sleep Apnoea-18 questionnaire and Oral Health Impact Profile-14 questionnaire will be traced, collected and measured. We will recruit 96 patients intofor the study. To assess differences, repeated multilevel linear mixed modelling analyses will be used.Ethics and dissemination This study has been granted ethical approval by the Ethics Committee of the School & Hospital of Stomatology, Wuhan University (approval No. 2023-D10). Written informed consent will be obtained from the participants and their guardians. The results of the trial will be disseminated through academic conferences and journal publications.Trial registration number ChiCTR2300078833.

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD.Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1β in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot.Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors.Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.

Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.

Abstract Endotoxemia‐related acute liver injury has a poor prognosis and high mortality, and macrophage polarization plays a central role in the pathological process. Pregnane X receptor (PXR) serves as a nuclear receptor and xenosensor, safeguarding the liver from toxic stimuli. However, the effect and underlying mechanism of PXR activation on endotoxemic liver injury remain largely unknown. Here, the expression of PXR is reported in human and murine macrophages, and PXR activation modified immunotypes of macrophages. Moreover, PXR activation significantly attenuated endotoxemic liver injury and promoted macrophage M2 polarization. Macrophage depletion by GdCl3 confirmed the essential of macrophages in the beneficial effects observed with PXR activation. The role of PXR in macrophages is further validated using AAV8‐F4/80‐Pxr shRNA‐treated mice; the PXR‐mediated hepatoprotection is impaired, and M2 polarization enhancement is blunted. Additionally, treatment with PXR agonists inhibited lipopolysaccharide (LPS)‐induced M1 polarization and favored M2 polarization in BMDM, Raw264.7, and THP‐1 cells. Further analyses revealed an interaction between PXR and p‐STAT6 in vivo and in vitro. Moreover, blocking Pxr or Stat6 abolished the PXR‐induced polarization shift. Collectively, macrophage PXR activation attenuated endotoxin‐induced liver injury and regulated macrophage polarization through the STAT6 signaling pathway, which provided a potential therapeutic target for managing endotoxemic liver injury.

Objectives Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD.Methods This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis.Results Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model.Conclusions We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g−1 and 39.0 mg∙g−1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Introduction Class II malocclusion with mandibular retrognathia is a common complication of paediatric obstructive sleep apnoea (OSA), often accompanied by transverse maxillary deficiency. In early orthodontic treatment, a twin block (TB) is a regular functional appliance for correcting this malocclusion. For paediatric OSA, the most common risk factor is adenotonsillar hypertrophy (AHT). Untreated AHT may lead to the persistence and worsening of obstructive sleep-disordered breathing traits, including habitual mouth breathing. Additionally, the clockwise mandibular rotation associated with AHT-induced pharyngeal crowding can undermine the effectiveness and stability of TB treatment. Adenotonsillectomy (T&A) is currently the first-line treatment for paediatric OSA. This proposed trial will investigate the impact of T&A surgery timing on the efficacy and stability of TB functional treatment in children with class II mandibular retrognathia and ATH.Methods and analysis This will be a single-centre, parallel-group, superiority randomised controlled trial with participants randomised to intervention (T&A followed by TB treatment) or control arms (TB treatment followed by T&A) in a 1:1 ratio. A total of 40 patients aged 8–14 years, diagnosed with class II mandibular retrognathia and co-existing ATH-induced OSA, and indicated for both T&A surgery and TB treatment, will be recruited at the School and Hospital of Stomatology, Wuhan University. The primary outcomes will be the changes in the apnoea-hypopnoea index and the point A-nasion-point B angle from baseline to postorthodontic treatment between the two groups. Secondary outcomes will include other dental, skeletal, upper airway and soft tissue changes, as well as subjective sleep-related and oral-related quality of life. Outcome changes within each group and between groups will be analysed.Ethics and dissemination This study is approved by the Ethics Committee of the School and Hospital of Stomatology, Wuhan University (no. 2022-D07). The research findings will be faithfully disseminated through scientific conferences or published articles.Trial registration number ChiCTR2200061703 (https://www.chictr.org.cn).

Abstract The Prechtl General Movements Assessment (GMA) is increasingly recognized for its role in evaluating the integrity of the developing nervous system and predicting motor dysfunctions, particularly in conditions such as cerebral palsy (CP). However, the necessity for highly trained professionals has hindered the adoption of GMA as an early screening tool in some countries. In this study, we propose a deep learning-based motor assessment model (MAM) that combines infant videos and basic characteristics, with the aim of automating GMA at the fidgety movements (FMs) stage. MAM demonstrates strong performance, achieving an Area Under the Curve (AUC) of 0.967 during external validation. Importantly, it adheres closely to the principles of GMA and exhibits robust interpretability, as it can accurately identify FMs within videos, showing substantial agreement with expert assessments. Leveraging the predicted FMs frequency, a quantitative GMA method is introduced, which achieves an AUC of 0.956 and enhances the diagnostic accuracy of GMA beginners by 11.0%. The development of MAM holds the potential to significantly streamline early CP screening and revolutionize the field of video-based quantitative medical diagnostics.

Abstract Objectives To analyze the diagnostic value of the tonsil–oropharynx (T/O) ratio on lateral cephalograms for evaluating tonsillar hypertrophy (TH). Methods A cross-sectional study was performed on 185 consecutive children (101 males, 84 females; mean age 7.3 ± 1.4 years) seeking orthodontic treatment. The T/O ratios on lateral cephalograms were calculated following Baroni et al.’s method. Tonsil sizes were clinically determined according to the Brodsky grading scale. Spearman correlation coefficients between the T/O ratio and clinical tonsil size were calculated with the total sample and subgroups and then compared between subgroups. Diagnostic value was analyzed using the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive and negative predictive values, and accuracy. Results There was a strong correlation between the T/O ratio and clinical tonsil size in children (ρ = 0.73; P

Abstract Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.