An easy-operation aptasensor for simultaneous detection of multiple tumor-associated exosomal proteins based on multicolor fluorescent DNA nanoassemblies.

As a promising liquid biopsy biomarker, exosomes have demonstrated great potential and advantages in the noninvasive tumor diagnosis. However, an accurate and sensitive method for tumors-associated exosomes detection is scarce. Herein, we presented an easy-operation aptasensor which simultaneously detect multiple exosomal proteins by using multicolor fluorescent DNA nanoassemblies (FDNs) and CD63 aptamer-modified magnetic beads (MNPs-AptCD63). In this system, the FDNs were firstly constructed by encapsulating different quantum dots (QDs) into rolling circle amplification (RCA) products that contained different aptamer sequences. Thus, the FDNs could selectively recognize the different exosomal proteins captured by the MNPs-AptCD63, and achieve the multiplex and sensitive detection according to the fluorescence of QDs. Benefiting from the signal amplification capacity and high selectivity of FDNs, this aptasensor not only could detect exosomes as low as 650 particles/µL, but also showed accurate analysis in clinical samples. In addition, we can also achieve point-of-care testing (POCT) due to the simple analysis steps and naked-eye observable fluorescence of QDs under the ultraviolet irradiation. We believe that our aptasensor could provide a promising platform for exosomes-based personalized diagnosis and precise monitoring of human health.

Risk of pulmonary complications after video-assisted thoracoscopic pulmonary resection in children.

BACKGROUND: Postoperative pulmonary complications (PPCs) are associated with high mortality and morbidity rates. Children are more susceptible to PPCs owing to smaller functional residual capacity and greater closing volume. Risk factors of PPCs in children undergoing lung resection remain unclear. METHODS: This retrospective study enrolled children who underwent video-assisted thoracoscopic surgery between January 2018 and February 2023. The primary outcome was PPC occurrence. Multivariate logistic regression was used to analyze risk factors for PPCs. RESULTS: Overall, 640 children were analyzed; their median age was 7 (interquartile range: 5-11) months, and the median tidal volume was 7.66 (6.59-8.49) mL/kg. One hundred and seventeen (18.3%) developed PPCs. PPCs were independently associated with male sex (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.17-2.88; P=0.008), longer OLV duration (OR, 1.01; 95% CI, 1.0-1.01; P=0.001), and less surgeon's experience (OR, 1.67; 95% CI, 1.03-2.7; P=0.036). When low-tidal-volume cutoff was defined as <8 mL/kg, PEEP level was a protective factor for PPCs (OR, 0.83; 95% CI, 0.69-1.00; P=0.046). Additionally, PPCs were associated with increased hospital stay (P<0.001). CONCLUSIONS: Male sex, longer OLV duration, less surgeon's experience, and lower PEEP were risk factors of PPCs in children undergoing video-assisted thoracoscopic surgery. Our findings may serve as targets for prospective studies investigating specific ventilation strategies for children.

Association of SOGPI in mediating the effect of Phosphatidylcholine on polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, marked by hormonal imbalances and disruptions in glucose and lipid metabolism. Emerging research has indicated a correlation between lipids and PCOS, yet the specific lipid profiles or associated genes identified in various studies vary, and observational data alone cannot establish causation. Therefore, our study seeks to establish a causal association between lipidome and PCOS. METHODS: Data from genome-wide association studies, liposomes, metabolites, and PCOS-related information were collected. Four rounds of double-sample bidirectional intermediate Mendelian Randomization analyses including liposomes to disease, liposomes to metabolites, metabolites to disease, and reverse Mendelian Randomization analysis of lipids, total effect values and intermediary effect values were calculated. The proportion mediated by the intermediary effect was determined by dividing the intermediary effect value by the total effect value. RESULTS: The analyses revealed that three liposomes and nine metabolites were causally associated with PCOS. Specifically, phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol were identified as independent risk factors for PCOS through further Mendelian Randomization analysis. The risk of developing PCOS increased by 32% for every one standard deviation increase in phosphatidylcholine and by 17% for every one standard deviation increase in 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol. Furthermore, the study revealed that phosphatidylcholine can influence the development of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol acting as a mediator, explaining 4.97% of the effect. CONCLUSIONS: This study confirmed a causal relationship between phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol with PCOS, where phosphatidylcholine can influence the occurrence of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol as a mediator.

Effects of prophylactic nalbuphine on emergence agitation and postoperative pain in pediatric patients undergoing ENT surgery with sevoflurane anesthesia.

Background: Emergence agitation (EA) is a common complication in the pediatric population. This study aimed to investigate the effect of the prophylactic nalbuphine on EA in pediatric patients receiving sevoflurane anesthesia. Methods: The children undergoing ear, nose, and throat (ENT) surgery were administered 0.2 mg/kg nalbuphine (the nalbuphine group) or the same volume of normal saline (the control group) 5 min before the end of the surgery. The extubating time, time to eye-opening and duration of the post-anesthesia care unit (PACU) were recorded. Heart rate and blood pressure were monitored before and 5 min after nalbuphine administration. Pain was assessed using Face Legs Activity Cry and Consolability (FLACC) scales, and the drug-related postoperative complications (e.g., EA, delayed awakening, nausea and vomiting, and respiratory depression) were recorded. Results: One-hundred and thirty pediatric patients were randomly divided into nalbuphine and control groups (n = 65). The nalbuphine group showed a significantly lower incidence of EA than the control group (20% vs. 46.2%, P = 0.002). No significant differences between the two groups were observed in heart rate and blood pressure 5 min after nalbuphine administration (P > 0.05). No significant differences were observed between the two groups regarding extubating time, time to eye-opening, and duration of PACU. The FLACC scales demonstrated lower values in the nalbuphine group than in the control group during the initial 4 h after the surgery. However, the FLACC scales showed similar values between 5 and 12 h after the surgery. Conclusions: In summary, the results of this study demonstrated that prophylactic natbuphine could minimize the incidence of EA in pediatric patients following ENT surgery without increasing the extubating time and PACU duration. Clinical Trial Registration: http://www.chictr.org.cn, identifier [ChiCTR2300070046].

A potential trade-off between reproduction and enhancement of thermotolerance in Liriomyza trifolii populations driven by thermal acclimation.

The invasive pest, Liriomyza trifolii, poses a significant threat to ornamental and vegetable plants. It spreads rapidly and causes large-scale outbreaks with pronounced thermotolerance. In this study, we developed L. trifolii strains adapted to high temperatures (strains designated 35 and 40); these were generated from a susceptible strain (designated S) by long-term thermal acclimation to 35 °C and 40 °C, respectively. Age-stage, two-sex life tables, thermal preferences, critical thermal limits, knockdown behaviors, eclosion and survival rates as well as expression of genes encoding heat shock proteins (Hsps) were compared for the three strains. Our findings indicated that the thermotolerance of L. trifolii was enhanced after long-term thermal acclimation, which suggested an adaptive plastic response to thermal stress. A trade-off between reproduction and thermotolerance was observed under thermal stress, potentially improving survival of the population and fostering adaptionary changes. Acclimation at 35 °C improved reproductive performance and population density of L. trifolii, particularly by enhancing the fecundity of female adults and accelerating the speed of development. Although the 40 strain exhibited the highest developmental speed and greater thermotolerance, it incurred a larger reproductive cost. This study provides a theoretical framework for monitoring and controlling leafminers and understanding their evolutionary adaptation to environmental changes.

Lung-protective ventilation and postoperative pulmonary complications during pulmonary resection in children: A prospective, single-centre, randomised controlled trial.

BACKGROUND: Children are more susceptible to postoperative pulmonary complications (PPCs) due to their smaller functional residual capacity and higher closing volume; however, lung-protective ventilation (LPV) in children requiring one-lung ventilation (OLV) has been relatively underexplored. OBJECTIVES: To evaluate the effects of LPV and driving pressure-guided ventilation on PPCs in children with OLV. DESIGN: Randomised, controlled, double-blind study. SETTING: Single-site tertiary hospital, 6 May 2022 to 31 August 2023. PATIENTS: 213 children aged < 6 years, planned for lung resection secondary to congenital cystic adenomatoid malformation. INTERVENTIONS: Children were randomly assigned to LPV ( n  = 142) or control ( n  = 71) groups. Children in LPV group were randomly assigned to either driving pressure group ( n  = 70) receiving individualised positive end-expiratory pressure (PEEP) to deliver the lowest driving pressure or to conventional protective ventilation group ( n  = 72) with fixed PEEP of 5 cmH 2 O. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PPCs within 7 days after surgery. Secondary outcomes were pulmonary mechanics, oxygenation and mechanical power. RESULTS: The incidence of PPCs did not differ between the LPV (24/142, 16.9%) and the control groups (15/71, 21.1%) ( P  = 0.45). The driving pressure was lower in the driving pressure group than in the 5 cmH 2 O PEEP group (15 vs. 17 cmH 2 O; P   =  0.001). Lung compliance and oxygenation were higher while the dynamic component of mechanical power was lower in the driving pressure group than in the 5 cmH 2 O PEEP group. The incidence of PPCs did not differ between the driving pressure (11/70, 15.7%) and the 5 cmH 2 O PEEP groups (13/72, 18.1%) ( P   =  0.71). CONCLUSIONS: LPV did not decrease the occurrence of PPCs compared to non-protective ventilation. Although lung compliance and oxygenation were higher in the driving pressure group than in the 5 cmH 2 O PEEP group, these benefits did not translate into significant reductions in PPCs. However, the study is limited by a small sample size, which may affect the interpretation of the results. Future research with larger sample sizes is necessary to confirm these findings. TRIAL REGISTRATION: ChiCTR2200059270.

[Research progress in osthole for prevention and treatment of central nervous system diseases].

Central nervous system(CNS) disorders can significantly impact patients' daily lives, impairing their ability to work and imposing a substantial financial burden on their families. In recent years, the incidence of CNS diseases has shown a significant increase with the continuous improvement of the quality of life and the aging problem. Therefore, the search for new preventive and curative drugs has been a research hotspot for this group of diseases. Osthole(OST), isolated from Umbelliferae such as Cnidium monnieri, Angelica sinensis, and Heracleum hemsleyanum, possesses a variety of pharmacological effects such as neuroprotective, antioxidant, anti-inflammatory, and antithrombotic effects. There is increasing evidence that OST has demonstrated significant preventive and curative effects in various CNS disease models. This paper systematically reviewed the research progress of OST in preventing and treating CNS diseases by reviewing domestic and international literature to provide more in-depth theoretical support for the future clinical application of OST in the prevention and treatment of CNS diseases.

Rule-based natural language processing to examine variation in worsening heart failure hospitalizations by age, sex, race and ethnicity, and left ventricular ejection fraction.

BACKGROUND: Prior studies characterizing worsening heart failure events (WHFE) have been limited in using structured healthcare data from hospitalizations, and with little exploration of sociodemographic variation. The current study examined the impact of incorporating unstructured data to identify WHFE, describing age-, sex-, race and ethnicity-, and left ventricular ejection fraction (LVEF)-specific rates. METHODS: Adult members of Kaiser Permanente Southern California (KPSC) with a HF diagnosis between 2014 and 2018 were followed through 2019 to identify hospitalized WHFE. The main outcome was hospitalizations with a principal or secondary HF discharge diagnosis meeting rule-based Natural Language Processing (NLP) criteria for WHFE. In comparison, we examined hospitalizations with a principal discharge diagnosis of HF. Age-, sex-, and race and ethnicity-adjusted rates per 100 person-years (PY) were calculated among age, sex, race and ethnicity (non-Hispanic (NH) Asian/Pacific Islander [API], Hispanic, NH Black, NH White) and LVEF subgroups. RESULTS: Among 44,863 adults with HF, 10,560 (23.5%) had an NLP-defined, hospitalized WHFE. Adjusted rates (per 100 PY) of WHFE using NLP were higher compared to rates based only on HF principal discharge diagnosis codes (12.7 and 9.3, respectively), and this followed similar patterns among subgroups, with the highest rates among adults ≥75 years (16.3 and 11.2), men (13.2 and 9.7), and NH Black (16.9 and 14.3) and Hispanic adults (15.3 and 11.4), and adults with reduced LVEF (16.2 and 14.0). Using NLP disproportionately increased the perceived burden of WHFE among API and adults with mid-range and preserved LVEF. CONCLUSION: Rule-based NLP improved the capture of hospitalized WHFE above principal discharge diagnosis codes alone. Applying standardized consensus definitions to EHR data may improve understanding of the burden of WHFE and promote optimal care overall and in specific sociodemographic groups.

A cyclic trinuclear silver complex for photosynthesis of hydrogen peroxide.

The development of metal complexes for photosynthesis of hydrogen peroxide (H2O2) from pure water and oxygen using solar energy, especially in the absence of any additives (e.g., acid, co-catalysts, and sacrificial agents), is a worthwhile pursuit, yet still remains highly challenging. More importantly, the O2 evolution from the water oxidation reaction has been impeded by the classic bottleneck, the photon-flux-density problem of sunlight that could be attributed to rarefied solar radiation for a long time. Herein, we reported synthesis of boron dipyrromethene (BODIPY)-based cyclic trinuclear silver complexes (Ag-CTC), and they exhibited strong visible-light absorption ability, a suitable energy bandgap, excellent photochemical properties and efficient charge separation ability. The integration of BODIPY motifs as oxygen reduction reaction sites and silver ions as water oxidation reaction sites allows Ag-CTC to photosynthesize H2O2 either from pure water or from sea water in the absence of any additives with a high H2O2 production rate of 183.7 and 192.3 µM h-1, which is higher than that of other reported metal-based photocatalysts. The photocatalytic mechanism was systematically and ambiguously investigated by various experimental analyses and density functional theory (DFT) calculations. Our work represents an important breakthrough in developing a new Ag photocatalyst for the transformation of O2 into H2O2 and H2O into H2O2.

Piperidine-based ionic liquid additive with electrostatic shielding and redox activity enabling advanced lithium-oxygen batteries.

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

The Metabolomic Profiling of the Flavonoid Compounds in Red Wine Grapes and the Impact of Training Systems in the Southern Subtropical Region of China.

Flavonoids play an important role in forming wine grapes and wine quality characteristics. The flavonoids of three winter red wine grapes, Yeniang No. 2 (YN2), Marselan (Mar), and Guipu No. 6 (GP6), were analyzed by ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS). Furthermore, the flavonoids in GP6 grapevines using two types of training systems, namely, trellis (T) and espaliers (E), were also compared in this study. Overall, 196 flavonoid metabolites, including 96 flavones, 38 flavonols, 19 flavanones, 18 polyphenols, 15 anthocyanins, 7 isoflavones, and 3 proanthocyanidins, were identified. The flavonoid profiles were remarkably different among these three grape varieties, while they did not change much in the GP6 managed on trellis and espaliers. Grape varieties with different genetic backgrounds have their own unique flavonoid profiles. Compared with Mar-T, isoflavones and flavonols presented higher contents in GP6-T and YN2-T, which mainly contain glycitein, genistin, calycosin, kaempferide, isotrifoliin, and ayanin. The anthocyanin content was significantly higher in YN2-T than in the other two varieties. YN2 and GP6-T present a more stable color, with significantly more acetylated diglucosides and methylated anthocyanins in YN2-T and GP6-T than in Mar-T. Notably, GP6 had more varied flavonoids and the better characteristics to its flavonoid profile out of these three varieties, due to it containing a higher number of anthocyanins, flavone, and flavonols and the greatest number of different flavonoid metabolites (DFMs), with higher contents than YN2 and Mar. Compared with the trellis training system, the espaliers training system increased the content of flavonoids detected in GP6 grape berries; however, the composition of flavonoids strictly depends on the grape variety.

Novel humanized monoclonal antibodies against ROR1 for cancer therapy.

BACKGROUND: Overexpression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) contributes to cancer cell proliferation, survival and migration, playing crucial roles in tumor development. ROR1 has been proposed as a potential therapeutic target for cancer treatment. This study aimed to develop novel humanized ROR1 monoclonal antibodies and investigate their anti-tumor effects. METHODS: ROR1 expression in tumor tissues and cell lines was analyzed by immunohistochemistry and flow cytometry. Antibodies from mouse hybridomas were humanized by the complementarity-determining region (CDR) grafting technique. Surface plasmon resonance spectroscopy, ELISA assay and flow cytometry were employed to characterize humanized antibodies. In vitro cellular assay and in vivo mouse experiment were conducted to comprehensively evaluate anti-tumor activity of these antibodies. RESULTS: ROR1 exhibited dramatically higher expression in lung adenocarcinoma, liver cancer and breast cancer, and targeting ROR1 by short-hairpin RNAs significantly inhibited proliferation and migration of cancer cells. Two humanized ROR1 monoclonal antibodies were successfully developed, named h1B8 and h6D4, with high specificity and affinity to ROR1 protein. Moreover, these two antibodies effectively suppressed tumor growth in the lung cancer xenograft mouse model, c-Myc/Alb-cre liver cancer transgenic mouse model and MMTV-PyMT breast cancer mouse model. CONCLUSIONS: Two humanized monoclonal antibodies targeting ROR1, h1B8 and h6D4, were successfully developed and exhibited remarkable anti-tumor activity in vivo.

Reversible splenial lesion syndrome in Anti-N-methyl-D-aspartate receptor encephalitis.

Here we described an 18-year-old woman who were initially misdiagnosed as psychiatric disorders in a psychiatric institution. She was transferred to our neurological ward because of impaired consciousness. Neuronal antibody testing confirmed the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Cerebral magnetic resonance imaging (MRI) revealed a concomitant disorder named reversible splenial lesion syndrome (RESLES). After administration of combined immunotherapy, the patient recovered completely 3 months after discharge. To our knowledge, co-occurrence of RESLES and anti-NMDAR encephalitis was only described in two patients with teratoma and we provide another case without teratoma. We highlight that anti-NMDAR antibodies can be added to the multiple causes of RESLES. It is therefore imperative for clinicians to detect anti-neuronal antibodies in patients with RESLES to avoid missed diagnosis.

Visible-Light-Mediated Ring-Opening Geminal Dibromination of Alkenes via Alkoxy Radicals Enabled by Electron Donor-Acceptor Complex.

An electron donor-acceptor complex was utilized to generate alkoxy radicals from alcohols under mild conditions using visible light. This approach was combined with a hydroxybromination process to achieve the deconstructive functionalization of alkenes, leading to the production of geminal dibromides. Mechanistic investigations indicated the intermediacy of hypervalent iodine (III) compounds.

The impact of increasing ambient temperature on allergic rhinitis: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Global warming appears to initiate and aggravate allergic respiratory conditions via interaction with numerous environmental factors. Temperature, commonly identified as a factor in climate change, is important in this process. Allergic rhinitis, a common respiratory allergy, is on the rise and affects approximately 500 million individuals worldwide. The increasing ambient temperature requires evaluation regarding its influence on allergic rhinitis, taking into account regional climate zones. METHODS: A detailed search of PubMed, EMBASE, Scopus, Web of Science, MEDLINE, and CINAHL Plus databases, was conducted, encompassing observational studies published from 1991 to 2023. Original studies examining the relationship between increasing temperature and allergic rhinitis were assessed for eligibility followed by a risk of bias assessment. Random effects meta-analysis was utilized to measure the association between a 1 °C increase in temperature and allergic rhinitis-related outcomes. RESULTS: 20 studies were included in the qualitative synthesis, with nine of them subsequently selected for the quantitative synthesis. 20 included studies were rated as Level 4 evidence according to the Oxford Centre for Evidence-Based Medicine, and the majority of these reported good-quality evidence based on the Newcastle-Ottawa Quality Rating Scale. Using the Risk of Bias In Non-Randomized Studies of Exposure tool, the majority of studies exhibit a high risk of bias. Every 1 °C increase in temperature significantly raised the risk of allergic rhinitis-related outcomes by 29 % (RR = 1.26, 95 % CI: 1.11 to 1.50). Conversely, every 1 °C rise in temperature showed no significant increase in the odds of allergic rhinitis-related outcomes by 7 % (OR = 1.07, 95 % CI: 0.95 to 1.21). Subsequent subgroup analysis identified climate zone as an influential factor influencing this association. CONCLUSION: It is inconclusive to definitively suggest a harmful effect of increasing temperature exposure on allergic rhinitis, due overall very low certainty of evidence. Further original research with better methodological quality is required.

Assessing ultrasound probe stabilization for quantifying speech production contrasts using the Adjustable Laboratory Probe Holder for UltraSound (ALPHUS).

Ultrasound imaging of the tongue is biased by the probe movements relative to the speaker's head. Two common remedies are restricting or algorithmically compensating for such movements, each with its own challenges. We describe these challenges in details and evaluate an open-source, adjustable probe stabilizer for ultrasound (ALPHUS), specifically designed to address these challenges by restricting uncorrectable probe movements while allowing for correctable ones (e.g., jaw opening) to facilitate naturalness. The stabilizer is highly modular and adaptable to different users (e.g., adults and children) and different research/clinical needs (e.g., imaging in both midsagittal and coronal orientations). The results of three experiments show that probe movement over uncorrectable degrees of freedom was negligible, while movement over correctable degrees of freedom that could be compensated through post-processing alignment was relatively large, indicating unconstrained articulation over parameters relevant for natural speech. Results also showed that probe movements as small as 5 mm or 2 degrees can neutralize phonemic contrasts in ultrasound tongue positions. This demonstrates that while stabilized but uncorrected ultrasound imaging can provide reliable tongue shape information (e.g., curvature or complexity), accurate tongue position (e.g., height or backness) with respect to vocal tract hard structure needs correction for probe displacement relative to the head.

Modified Sanliangsan Improved Sjogren's Syndrome Complicated with Interstitial Lung Disease by Suppressing Serum MUC1 Levels.

OBJECTIVES: To clarify if the mechanism of Sanliangsan in improving Sjogren's syndrome complicated with interstitial lung disease (SS-ILD) involves MUC1 suppression, which is involved in SS-ILD pathogenesis. METHODS: Fifty-six patients were randomly divided into two groups receiving Sanliangsan prescription (SP) therapy and conventional therapy (western medicine). In-depth transcriptome profiles from a large database of SS-ILD patients were collected and analyzed to identify candidate genes involved in SS pathogenesis. Clinical symptom scores, metabolic compositions, lung HRCT (high-resolution computed tomography) scores, and serum MUC1 levels were compared between the two groups before and after treatment. Network pharmacology, molecular docking, and ITC assays were performed to identify bioactive compounds of SP in improving SS. Metabolome analyzed the metabolic composition of serum associated with SS-ILD before and after SP treatment. RESULTS: Transcriptome results identified the involvement of abnormal expression of genes relevant to the immune system, inflammatory responses, and signaling pathways. Numerous genes, including CD58, CD86, CTLA4, CXCL8, STAT1, and especially MUC1, were involved in SS pathogenesis and could be used to diagnose SS-ILD early. Both treatments improved the lung HRCT scores and clinical symptoms of SS-ILD. The SP therapy improved SS-ILD more effectively than conventional therapy. Moreover, Sanliangsan prescription therapy reduced serum MUC1 levels and restored the abnormal metabolisms, improving the abnormal inflammatory and immune responses of patients. Eugenol directly interacted with MUC1, suppressed related genes, and was the bioactive compound of SP. SP could partially restore the abnormal metabolisms associated with SS-ILD pathogenesis. CONCLUSION: Based on conventional Western medicine treatment, modified Sanliangsan can significantly improve the clinical symptoms, signs, and lung function of patients; the mechanism may be due to eugenol and related to MUC1 regulation.