Network pharmacology-and molecular docking-based investigation of Danggui blood-supplementing decoction in ischaemic stroke.

Danggui blood-supplementing decoction (DBsD) is an herbal preparation treating several diseases including stroke. The present study sought to investigate the potential mechanism of DBsD in ischaemic stroke (IS) using network pharmacology, molecular docking, and cell experiment. Based on the protein-protein (PPI) network analysis, MAPK1 (0.51, 12), KNG1 (0.57, 28), and TNF (0.64, 39) were found with relatively good performance in degree and closeness centrality. The functional enrichment analysis revealed that DBsD contributed to IS-related biological processes, molecule function, and presynaptic/postsynaptic cellular components. Pathway enrichment indicated that DBsD might protect IS by modulating multi-signalling pathways including the sphingolipid signalling pathway. Molecular docking verified the stigmasterol-KNG1, bifendate-TNF, and formononetin-MAPK1 pairs. Cell experiments confirmed the involvement of KNG1 and sphingolipid signalling pathway in hippocampal neuronal cell apoptosis. This study showed that DBsD can protect neuronal cell injury after IS through multiple components, multiple targets, and multiple pathways.

Electrochemiluminescence of Ultrasmall Silica Nanoparticles from Size Modulation and Multipath Surface State Adjustment for Ultrasensitive HIV-DNA Fragment Detection.

Here, ultrasmall SiO2 nanoparticles (u-SiO2 NPs, <5 nm) with obvious electrochemiluminescence (ECL) phenomenon, which was absent for conventional silica nanoparticles (c-SiO2 NPs), were reported. In a finite ultrasmall volume, the u-SiO2 NPs exhibited increasing ground state energy and higher optical absorption strength due to the electron-hole confinement model and favored catalyzing the reaction through the rapid diffusion of bulk charge, resulting in apparent ECL emission. Then, Zn2+-induced u-SiO2 nanoaggregates (Zn/u-SiO2-Ov nAGG) were synthesized and exhibited improved ECL performance via multipath surface state adjustment of u-SiO2 from several aspects, including aggregation-induced ECL, the generation of oxygen vacancy (Ov), and more positive surface charge. In addition, an ECL biosensor was constructed for ultrasensitive human immunodeficiency virus-related deoxyribonucleic acid detection from 100 aM to 1 nM with a low limit of 50.48 aM, combining the ECL luminescence of Zn/u-SiO2-Ov nAGG with three-dimensional DNA nanomachine-mediated multioutput amplification for enhanced accuracy and sensitivity compared to the single-output method. Therefore, exploring the ECL of ultrasmall nanoparticles via the adjustment of size and surface state provided a valuable indication to a wider investigation and application of novel ECL materials for clinical diagnostic.

Solvent Regulation Induced Cathode Aggregation-Induced Electrochemiluminescence of Tetraphenylethylene Nanoaggregates for Ultrasensitive Zearalenone Analysis.

Zearalenone (ZEN) is an extremely hazardous chemical widely existing in cereals, and its high-sensitivity detection possesses significant significance to human health. Here, the cathodic aggregation-induced electrochemiluminescence (AIECL) performance of tetraphenylethylene nanoaggregates (TPE NAs) was modulated by solvent regulation, based on which an electrochemiluminescence (ECL) aptasensor was constructed for sensitive detection of ZEN. The aggregation state and AIECL of TPE NAs were directly and simply controlled by adjusting the type of organic solvent and the fraction of water, which solved the current shortcomings of low strength and weak stability of the cathode ECL signal for TPE. Impressively, in a tetrahydrofuran-water mixed solution (volume ratio, 6:4), the relative ECL efficiency of TPE NAs reached 16.03%, which was 9.2 times that in pure water conditions, and the maximum ECL spectral wavelength was obviously red-shifted to 617 nm. In addition, "H"-shape DNA structure-mediated dual-catalyzed hairpin self-assembly (H-D-CHA) with higher efficiency by the synergistic effect between the two CHA reactions was utilized to construct a sensitive ECL aptasensor for ZEN analysis with a low detection limit of 0.362 fg/mL. In conclusion, solvent regulation was a simple and efficient method for improving the performance of AIECL materials, and the proposed ECL aptasensor had great potential for ZEN monitoring in food safety.

Change in neighborhood socioeconomic status and childhood weight status and body composition from birth to adolescence.

BACKGROUND: We aim to assess the associations between the change in neighborhood socioeconomic score (SES) between birth and 6 years and childhood weight status and body composition from 6 to 13 years. METHODS: Data for 3909 children from the Generation R Study, a prospective population-based cohort in the Netherlands were analyzed. The change in neighborhood SES between birth and 6 years was defined as static-high, static-middle, static-low, upward, and downward mobility. Child body mass index (BMI), overweight and obesity (OWOB), fat mass index (FMI) and lean mass index (LMI) were measured at age 6, 10, and 13 years. The associations were explored using generalized estimating equations. The effect modification by child sex was examined. RESULTS: In total, 19.5% and 18.1% of children were allocated to the upward mobility and downward mobility neighborhood SES group. The associations between the change in neighborhood SES and child weight status and body composition were moderated by child sex (p < 0.05). Compared to girls in the static-high group, girls in the static-low group had relatively higher BMI-SDS (ß, 95% confidence interval (CI): 0.24, 0.09-0.40) and higher risk of OWOB (RR, 95% CI: 1.98, 1.35-2.91), together with higher FMI-SDS (ß, 95% CI: 0.27, 0.14-0.41) and LMI-SDS (ß, 95% CI: 0.18, 0.03-0.33). The associations in boys were not significant. CONCLUSIONS: An increased BMI and fat mass, and higher risk of OWOB from 6 to 13 years were evident in girls living in a low-SES neighborhood or moving downward from a high- to a low-SES neighborhood. Support for children and families from low-SES neighborhoods is warranted.

Climate-associated variation in the drivers of benthic macroinvertebrate species-area relationships across shallow freshwater lakes.

The island species-area relationship (ISAR) describes how species richness increases with increasing area of a given island or island-like habitat, such as freshwater lakes. While the ISAR is one of the most common phenomena observed in ecology, there is variation in both the form of the relationship and its underlying mechanisms. We compiled a global data set of benthic macroinvertebrates from 524 shallow freshwater lakes, ranging from 1 to 293,300 ha in area. We used individual-based rarefaction to determine the degree to which ISAR was influenced by mechanisms other than passive sampling (larger islands passively sample more individuals from the regional pool and, therefore, have more species than smaller islands), which would bias results away from expected relationships between rarefied species richness (and other measures that capture relative abundances) and lake area. We also examined how climate may alter the shape of the ISARs. We found that both rarefied species richness (the number of species standardized by area or number of individuals) and a measure of evenness emphasizing common species exhibit shallow slopes in relationships with lake area, suggesting that the expected ISARs in these lakes most likely result from passive sampling. While there was considerable variation among ISARs across the investigated lakes, we found an overall positive rarefied ISAR for lakes in warm (i.e. tropical/subtropical) regions (n = 195), and in contrast, an overall negative rarefied ISAR in cool (i.e. north temperate) lakes (n = 329). This suggested that mechanisms beyond passive sampling (e.g. colonization-extinction dynamics and/or heterogeneity) were more likely to operate in warm lakes. One possible reason for this difference is that the area-dependent intensity of fish predation, which can lead to flatter ISARs, is weaker in warmer relative to cooler lakes. Our study illustrates the importance of understanding both the pattern and potential processes underlying the ISARs of freshwater lakes in different climatic regions. Furthermore, it provides a baseline for understanding how further changes to the ecosystem (i.e. in lake area or climate) might influence biodiversity patterns.

Clinical application of combination [11C]C-methionine and [13N]N-ammonia PET/CT in recurrent functional pituitary adenomas with negative MRI or [18F]F-FDG PET/CT.

BACKGROUND: We assessed the value of positron emission tomography/computed tomography (PET/CT) with [13N]N-ammonia ([13N]N-NH3) and [11C]C-methionine ([11C]C-MET) for the evaluation and management of recurrent secreting pituitary adenoma, which could not be detected by magnetic resonance imaging (MRI) or fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET. METHODS: Nine consecutive patients with biochemical and clinical evidence of active recurrent tumor not detected by MRI and [18F]F-FDG PET were enrolled in this study. All of the patients underwent [13N]N-NH3 and [11C]C-MET PET/CT, after which the pattern of tracer uptake was studied, the tumor position was located, and a clinical decision was made. RESULTS: In general, [11C]C-MET had a higher uptake in pituitary adenomas (PAs) than that in pituitary tissues, while [13N]N-NH3 had a higher uptake in pituitary tissue than in pituitary adenomas. Increased [11C]C-MET uptake was observed in all nine PAs and three pituitary tissues, while all pituitary tissues and only one pituitary adenoma showed increased [13N]N-NH3 uptake. Four patients had concordant imaging and surgical findings indicative of biochemical remission without hypopituitarism after treatment. Radiotherapy was adopted in two patients, medication in another two, and follow-up observation in one case. CONCLUSION: Combined [11C]C-MET and [13N]N-NH3 PET/CT is effective in the differentiation of PAs from pituitary tissue in recurrent functional PAs with negative MRI or [18F]F-FDG PET. These results provide a valuable reference for further disease management.

Endoscopic endonasal transsphenoidal approach improves endocrine function and surgical outcome in primary craniopharyngioma resection: a systematic review and meta-analysis.

BACKGROUND: Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs. OBJECT AND METHOD: We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management. RESULT: Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21-22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31-0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12-0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06-0.15, p < 0.001) and visual outcomes (visual improvement: OR = 3.42, 95%CI: 1.24-9.40, p = 0.017; visual deficit: OR = 0.30, 95%CI: 0.26-0.35) with decreases in postoperative stroke (OR = 0.58, 95%CI: 0.51-0.66, p < 0.001), hydrocephalus, and infections (OR = 0.32, 95%CI: 0.24-0.42, p < 0.001). CONCLUSION: Compared with the traditional TCA in primary CP resection, the development and wide application of EEA optimistically decreased the recurrence rate of CP, alleviated hypopituitarism with improvement in the GTR rate of pediatric patients, and significantly improved the visual outcomes, hydrocephalus, postoperative stroke, survival, and infection rates of the patients. Therefore, EEA is an optimal approach for primary CP resection.

Medial Patellofemoral Complex Reconstruction (Combined Reconstruction of Medial Patellofemoral Ligament and Medial Quadriceps Tendon-Femoral Ligament) With Semitendinosus Autograft Resulted in Similar Clinical and Radiographic Outcomes to Medial Patellofemoral Ligament Reconstruction in Treating Recurrent Patellar Dislocation.

PURPOSE: To compare clinical and radiographic outcomes of medial patellofemoral ligament reconstruction (MPFL-R) and medial patellofemoral complex reconstruction (MPFC-R) for recurrent patellar dislocation. Outcome measures were compared based on the Insall-Salvati index. METHODS: Patients who were diagnosed with recurrent patellar dislocation and underwent either MPFL-R or MPFC-R (combined reconstruction of MPFL and medial quadriceps tendon-femoral ligament) were retrospectively analyzed. Group allocation was based on surgical procedure and patient characteristics were collected. Clinical assessments included patient-reported outcome measures (PROMs) and return-to-sports rates. Minimal clinically important difference analysis was performed. A subgroup analysis of PROMs was carried out between patients with an Insall-Salvati index ≤1.2 versus >1.2. The patellar tilt angle, lateral patellar displacement, and bisect offset ratio were measured pre- and postsurgery. Functional failures and complications were assessed. RESULTS: Overall, 70 patients (72 knees) in the MPFL-R group and 58 patients (61 knees) in the MPFC-R group were included. Patient characteristics were comparable between the groups. At a minimum follow-up of 24 (mean, 50.6 ± 22.1) months, all PROMs were substantially improved (P < .001), without significant intergroup differences. The percentages of patients reaching the minimal clinically important difference were similar after MPFL-R and MPFC-R: 98.6% versus 93.4% (International Knee Documentation Committee), 97.2% versus 98.4% (Lysholm), 98.6% versus 100% (Kujala), and 77.8% versus 72.1% (Tegner). The subgroup analysis based on patellar height and the return-to-sport rates also suggested comparable results. Radiographic evaluation demonstrated significantly smaller lateral patellar displacements (P = .004) and bisect offset ratios (P < .001) but similar patellar tilt angles after MPFC-R. Four (5.6%) patients receiving MPFL-R and 2 (3.3%) patients receiving MPFC-R reported recurrence of functional instability, without statistically significant difference. CONCLUSIONS: MPFC-R resulted in similar overall clinical and radiographic outcomes to MPFL-R in treating recurrent patellar dislocation. MPFC-R might not provide additional benefits for patients with an Insall-Salvati index >1.2. LEVEL OF EVIDENCE: Level IV, therapeutic, retrospective cohort study.

High resolution imaging of acoustic orbital angular momentum wave based on orthogonal matching tracking.

The orbital angular momentum (OAM) wave has shown great potential for improving radar imaging and underwater communication performance due to its helical wavefront phase and infinite orthogonal modes. However, there are currently no known applications of this technology in underwater imaging. In this paper, we employed acoustic OAM wave for underwater imaging and established transceiver signal models using the uniform circular array. We concurrently achieved two-dimensional imaging of azimuth and elevation angles, which differs from radar imaging. We proposed a matching process for the echo signal in the modal domain, the OAM wave beam image's sidelobe decreased by 7.9 dB in the elevation direction and 6.1 dB in the azimuth direction compared to the plane wave, with the mainlobe decreased by 0.2° in the elevation direction and 0.4° in the azimuth direction. Furthermore, this paper introduced OAM wave high-resolution image reconstruction based on the orthogonal matching pursuit (OMP) algorithm. Finally, we implemented broadband acoustic OAM wave for underwater imaging and introduced an image reconstruction method based on the modal domain OMP algorithm. Simulation results demonstrate that the use of OAM wave in underwater imaging is feasible, and the proposed scheme can achieve high-resolution imaging.

Good clinical outcomes of anterior cruciate ligament reconstruction in patients over 60 years of age.

PURPOSE: To evaluate the clinical outcomes following arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) in patients over 60 years and to investigate the potential impact of preoperative osteoarthritis (OA) on these outcomes. METHODS: A retrospective study included ACL-injured patients over 60 years who underwent primary arthroscopic ACLR between 2010 and 2020. The Lysholm score and the International Knee Documentation Committee (IKDC) score were assessed preoperatively and at the final follow-up. The Tegner activity scale was performed to evaluate patients' activity levels. Data on return to sports, patient satisfaction, subsequent injuries and complications were collected. Preoperative radiographs were used to grade OA according to the Kellgrene-Lawrence classification. Correlation analysis between OA and clinical outcomes was performed. The rates of achieving the minimal clinically significant difference and patient-acceptable symptoms state were documented. RESULTS: A total of 37 patients were included in this study. The mean age at surgery was 62.3 ± 2.3 years, with a mean follow-up of 6.3 ± 3.2 years (range: 2.1-12.4). Patients showed statistically significant (all p < 0.001) improvements in the mean IKDC (38.9 ± 9.4-66.8 ± 12.5), Lysholm (48.8 ± 15.4-83.0 ± 12.8) and Tegner (1-3) scores. Fourteen patients (37.8%) returned to sports. No correlation was observed between the degree of preoperative OA and clinical outcomes (n.s.). CONCLUSION: Patients over 60 years with symptomatic ACL-deficient knees could benefit from ACLR, even when mild to moderate OA is present preoperatively. LEVEL OF EVIDENCE: Level IV.

[A prospective cohort study of association between early childhood body mass index trajectories and the risk of overweight].

OBJECTIVE: To compare the association between body mass index (BMI) trajectories determined by different methods and the risk of overweight in early childhood in a prospective cohort study, and to identify children with higher risk of obesity during critical growth windows of early childhood. METHODS: A total of 1 330 children from Peking University Birth Cohort in Tongzhou (PKUBC-T) were included in this study. The children were followed up at birth, 1, 3, 6, 9, 12, 18, and 24 months and 3 years of age to obtain their height/length and weight data, and calculate BMI Z-score. Latent class growth mixture modeling (GMM) and longitudinal data-based k-means clustering algorithm (KML) were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths. Linear regression was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age. The predictive performance of early childhood BMI trajectories determined by different methods in predicting the risk of overweight (BMI Z-score > 1) at 3 years was compared using the average area under the curve (AUC) of 5-fold cross-validation in Logistic regression models. RESULTS: In the study population included in this research, the three-category trajectories determined using GMM were classified as low, medium, and high, accounting for 39.7%, 54.1%, and 6.2% of the participants, respectively. The two-category trajectories determined using the KML method were classified as low and high, representing 50. 3% and 49. 7% of the participants, respectively. The three-category trajectories determined using the KML method were classified as low, medium, and high, accounting for 31.1%, 47.4%, and 21.5% of the participants, respectively. There were certain differences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods. Linear regression analysis found that after adjusting for maternal ethnicity, educational level, delivery mode, parity, maternal age at delivery, gestational week at delivery, children' s gender, and breastfeeding at 1 month of age, the association between the high trajectory group in the three-category trajectories determined by the KML method (manifested by a slightly higher BMI at birth, followed by rapid growth during infancy and a stable-high BMI until 24 months) and BMI Z-scores at 3 years was the strongest. Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years. The results were basically consistent after additional adjustment for the high bound score of the child' s diet balanced index, average daily physical activity time, and screen time. CONCLUSION: This study used different methods to identify early childhood BMI trajectories with varying characteristics, and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood. This provides scientific evidence for selecting appropriate methods to define early childhood BMI trajectories.

Cardiac involvement in muscular dystrophies: Role of myocardial perfusion imaging.

Technetium-99m-methoxy isobutyl isonitrile (99mTc-MIBI) myocardial perfusion imaging (MPI) is a functional imaging method with relatively poor specificity but high sensitivity. We present 48-year-old man with cardiac involvement due to muscular dystrophies (MD). Myocardial perfusion imaging rest images revealed regional myocardial perfusion decrease in multiple walls, enlarged heart and decreased left ventricular systolic function. The lesion location of MPI was consistent with that seen on CMR. Our case showed MPI was useful for detection and evaluation of the MD patient with cardiac involvement. In addition, imaging findings in combination with clinical history and other data are important. The case highlight is thevalue of MPI in myocardiopathy.

[Mechanism of resveratrol in protecting ovary in poor ovarian response mice by regulating Hippo signaling pathway].

This study observed the protective effect of resveratrol(Res) on ovarian function in poor ovarian response(POR) mice by regulating the Hippo signaling pathway and explored the potential mechanism of Res in inhibiting ovarian cell apoptosis. Female mice with regular estrous cycles were randomly divided into a blank group, a model group, and low-and high-dose Res groups(20 and 40 mg·kg~(-1)), with 20 mice in each group. The blank group received an equal volume of 0.9% saline solution by gavage, while the model group and Res groups received suspension of glycosides of Triptergium wilfordii(GTW) at 50 mg·kg~(-1) by gavage for two weeks to induce the model. After modeling, the low-and high-dose Res groups were continuously treated with drugs by gavage for two weeks, while the blank group and the model group received an equal volume of 0.9% saline solution by gavage. Ovulation was induced in all groups on the day following the end of treatment. Finally, 12 female mice were randomly selected from each group, and the remaining eight female mice were co-housed with male mice at a ratio of 1∶1. Changes in the estrous cycle of mice were observed using vaginal cytology smears. The number of ovulated eggs, ovarian wet weight, ovarian index, and pregnancy rate of mice were measured. The le-vels of anti-Mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in serum were determined using enzyme-linked immunosorbent assay(ELISA). Ovarian tissue morphology and ovarian cell apoptosis were observed using hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining, respectively. The protein expression levels of yes-associated protein(YAP) 1 and transcriptional coactivator with PDZ-binding motif(TAZ) were detected by immunohistochemistry(IHC), while the changes in protein expression levels of mammalian sterile 20-like kinase(MST) 1/2, large tumor suppressor(LATS) 1/2, YAP1, TAZ, B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were determined by Western blot. The results showed that compared with the blank group, the model group had an increased rate of estrous cycle disruption in mice, a decreased number of normally developing ovarian follicles, an increased number of blocked ovarian follicles, increased ovarian granulosa cell apoptosis, decreased ovulation, reduced ovarian wet weight and ovarian index, increased serum FSH and LH levels, decreased AMH and E_2 levels, decreased protein expression levels of YAP1 and TAZ in ovarian tissues, increased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and decreased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Additionally, the number of embryos per litter significantly decreased after co-housing. Compared with the model group, the low-and high-dose Res groups exhibited reduced estrous cycle disruption rates in mice, varying degrees of improvement in the number and morphology of ovarian follicles, reduced numbers of blocked ovarian follicles, improved ovarian granulosa cell apoptosis, increased ovulation, elevated ovarian wet weight and ovarian index, decreased serum FSH and LH levels, increased AMH and E_2 levels, elevated protein expression levels of YAP1 and TAZ in ovarian tissues, decreased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and increased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Furthermore, the number of embryos per litter increased to varying degrees after co-housing. In conclusion, Res effectively inhibits ovarian cell apoptosis in mice and improves ovarian responsiveness. Its mechanism may be related to the regulation of key molecules in the Hippo pathway.

Strategies and interventions for healthy adolescent growth, nutrition, and development.

Adolescence is a pivotal point in the life course, characterised by transformative physical, cognitive, and emotional growth, an openness to change, and a drive to reshape the social environment. It offers unique opportunities to adopt changes in diet and physical activity that can persist into later life. Yet pre-existing nutritional problems, including micronutrient deficiencies, food insecurity, and poor-quality diets, persist at the same time as adolescents face the rapid emergence of an obesity epidemic. Adolescent growth and nutrition has been largely overlooked in intervention and policy research. Most intervention studies have emphasised micronutrient supplementation, with few taking into account the multiple drivers of adolescent diets. This Series paper highlights that effective interventions and policies will need to cut across sectors; be supported by multifaceted and multilevel policy; and extend across education, health, food systems, social protection, and digital media. Better data standardisation and systems will be essential in coordinating and monitoring these responses. In a context of shifts in planetary ecosystems and commercial drivers, resilient food systems will need to both ensure access to healthy and affordable foods and provide the infrastructure and incentives for continuing physical activity. Intergenerational partnerships with young people will be essential in bringing about transformative change and ensuring that food policies reflect their needs and aspirations.

High-Density N-Vacancy-Induced Multipath Electrochemiluminescence Improvement of 3D g-C3N4 for Ultrasensitive MiRNA-222 Analysis.

Using dissolved O2 as the cathodic co-reactant of three-dimensional (3D) g-C3N4 is a convenient method to improve the electrochemiluminescence (ECL) signal, but it still suffers the disadvantages of limited luminous efficiency of 3D g-C3N4 and low content, low reactivity, and instability of dissolved O2. Here, N vacancy with high density was first introduced into the structure of 3D g-C3N4 (3D g-C3N4-NV), which could conveniently realize multipath ECL improvement by simultaneously solving the above shortcomings effectively. Specifically, N vacancy could change the electronic structure of 3D g-C3N4 to broaden its band gap, increase fluorescence (FL) lifetime, and accelerate electron transfer rate, obviously improving the luminous efficiency of 3D g-C3N4. Meanwhile, N vacancy made the excitation potential of 3D g-C3N4-NV to shift from -1.3 to -0.6 V, effectively weakening the electrode passivation. Moreover, the adsorption capacity of 3D g-C3N4-NV was obviously enhanced, which could make the dissolved O2 enrich around 3D g-C3N4-NV. And massive active NV sites of 3D g-C3N4-NV could promote O2 to more efficiently convert to reactive oxygen species (ROS) that were key intermediates in ECL generation. Using the newly proposed 3D g-C3N4-NV-dissolved O2 system as an ECL emitter, an ultrasensitive target conversion biosensor was constructed for miRNA-222 detection. The fabricated ECL biosensor exhibited satisfactory analytical performance for miRNA-222 with a detection limit of 16.6 aM. The strategy achieved multipath ECL improvement by introducing high-density N vacancy simply in the 3D structure of g-C3N4 and could open a new horizon for developing a high-performance ECL system.

Ultra-Sensitive MicroRNA Biosensor Based on Strong Aggregation-Induced Electrochemiluminescence from Bidentate Ligand-Stabilized Copper Nanoclusters in Polymer Hydrogel.

Herein, dihydrolipoic acid (DHLA)-stabilized copper nanoclusters (Cu NCs) with high aggregation-induced electrochemiluminescence (AIECL) in polymer hydrogel were prepared to construct an ECL biosensor for detection of microRNA-21. DHLA, a small molecule ligand with two sulfhydryl groups, was used as a protective agent to synthesize Cu NCs, which improved the ECL stability and intensity of Cu NCs. Furthermore, the Cu NCs were loaded into the (PVP-PVA)hydrogel to form the DHLA-Cu NCs@(PVP-PVA)hydrogel composite, which showed effective AIECL performance. The confinement of Cu NCs into the hydrogel increased the local concentration of Cu NCs, which could not only prevent oxides from entering the copper core, but also limit the vibration to reduce non-radiative transitions of Cu NCs, leading to a distinct AIECL emission. Then, combined with the self-priming clip trigger isothermal amplification (SCTIA) technology, an ECL biosensor was constructed to realize the sensitive detection of miRNA-21. Interestingly, SCTIA technology was a simple and efficient strategy that realized multiple-cycle amplified processes to acquire a mass of output DNA, achieving remarkable signal amplification. Therefore, this strategy provided an efficient approach in the preparation of Cu NCs with high AIECL emission and target amplification technology, which might have promising potential in clinical application.

Aluminum(III)-Based Organic Nanofibrous Gels as an Aggregation-Induced Electrochemiluminescence Emitter Combined with a Rigid Triplex DNA Walker as a Signal Magnifier for Ultrasensitive DNA Assay.

Due to effective tackling of the problems of aggregation-caused quenching of traditional ECL emitters, aggregation-induced electrochemiluminescence (AIECL) has emerged as a research hotspot in aqueous detection and sensing. However, the existing AIECL emitters still encounter the bottlenecks of low ECL efficiency, poor biocompatibility, and high cost. Herein, aluminum(III)-based organic nanofibrous gels (AOGs) are used as a novel AIECL emitter to construct a rapid and ultrasensitive sensing platform for the detection of Flu A virus biomarker DNA (fDNA) with the assistance of a high-speed and hyper-efficient signal magnifier, a rigid triplex DNA walker (T-DNA walker). The proposed AOGs with three-dimensional (3D) nanofiber morphology are assembled in one step within about 15 s by the ligand 2,2':6',2″-terpyridine-4'-carboxylic acid (TPY-COOH) and cheap metal ion Al3+, which demonstrates an efficient ECL response and outstanding biocompatibility. Impressively, on the basis of loop-mediated isothermal amplification-generated hydrogen ions (LAMP-H+), the target-induced pH-responsive rigid T-DNA walker overcomes the limitations of conventional single or duplex DNA walkers in walking trajectory and efficiency due to the entanglement and lodging of leg DNA, exhibiting high stability, controllability, and walking efficiency. Therefore, AOGs with excellent AIECL performance were combined with a CG-C+ T-DNA nanomachine with high walking efficiency and stability, and the proposed "on-off" ECL biosensor displayed a low detection limit down to 23 ag·µL-1 for target fDNA. Also, the strategy provided a useful platform for rapid and sensitive monitoring of biomolecules, considerably broadening its potential applications in luminescent molecular devices, clinical diagnosis, and sensing analysis.

Microspore-expressed SCULP1 is required for p-coumaroylation of sporopollenin, exine integrity, and pollen development in wheat.

Sporopollenin is one of the most structurally sophisticated and chemically recalcitrant biopolymers. In higher plants, sporopollenin is the dominant component of exine, the outer wall of pollen grains, and contains covalently linked phenolics that protect the male gametes from harsh environments. Although much has been learned about the biosynthesis of sporopollenin precursors in the tapetum, the nutritive cell layer surrounding developing microspores, little is known about how the biopolymer is assembled on the microspore surface. We identified SCULP1 (SKS clade universal in pollen) as a seed plant conserved clade of the multicopper oxidase family. We showed that SCULP1 in common wheat (Triticum aestivum) is specifically expressed in the microspore when sporopollenin assembly takes place, localized to the developing exine, and binds p-coumaric acid in vitro. Through genetic, biochemical, and 3D reconstruction analyses, we demonstrated that SCULP1 is required for p-coumaroylation of sporopollenin, exine integrity, and pollen viability. Moreover, we found that SCULP1 accumulation is compromised in thermosensitive genic male sterile wheat lines and its expression partially restored exine integrity and male fertility. These findings identified a key microspore protein in autonomous sporopollenin polymer assembly, thereby laying the foundation for elucidating and engineering sporopollenin biosynthesis.

Adults in Northwest China experienced the largest outbreak of Japanese encephalitis in history 10 years after the Japanese encephalitis vaccine was included in the national immunization program: A retrospective epidemiological study.

Mainland China included Japanese encephalitis (JE) vaccine in the national immunization program in 2008 to control the JE epidemic. However, Gansu province in Western China experienced the largest JE outbreak since 1958 in 2018. We conducted a retrospective epidemiological study to explore the causes of this outbreak. We found that adults aged ≥20 years (especially those in rural areas) were the main JE cases in Gansu Province, with a significant increase in the JE incidence in older adults aged ≥60 years in 2017 and 2018. In addition, JE outbreaks in Gansu Province were mainly located in the southeastern region, while the temperature and precipitation in Gansu Province were gradually increasing in recent years, which made the JE epidemic areas in Gansu Province gradually spread to the western of Gansu Province. We also found that adults aged ≥20 years in Gansu Province had lower JE antibody positivity than children and infants, and the antibody positivity rate decreased with age. In the summer of 2017 and 2018, the density of mosquitoes (mainly the Culex tritaeniorhynchus) in Gansu Province was significantly higher than in other years, and the genotype of JEV was mainly Genotype-G1. Therefore, in the future JE control in Gansu Province, we need to strengthen JE vaccination for adults. Moreover, strengthening mosquito surveillance can provide early warning of JE outbreaks and the spread of epidemic areas in Gansu Province. At the same time, strengthening JE antibody surveillance is also necessary for JE control.

Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs): increased M2 macrophage infiltration and PD-L1 expression in PIT1-lineage subset.

PURPOSE: Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs) and application of current immunotherapy for refractory PitNETs remains debated. We aim to evaluate the immune landscape in different lineages of PitNETs and determine the potential role of pituitary transcription factors in reshaping the tumor immune microenvironment (TIME), thus promoting the application of current immunotherapy for aggressive and metastatic PitNETs. METHODS: Immunocyte infiltration and expression patterns of immune checkpoint molecules in different lineages of PitNETs were estimated via in silico analysis and validated using an IHC validation cohort. The correlation between varying immune components with clinicopathological features was assessed in PIT1-lineage PitNETs. RESULTS: Transcriptome profiles from 210 PitNETs/ 8 normal pituitaries (NPs) and immunohistochemical validations of 77 PitNETs/6 NPs revealed a significant increase in M2-macrophage infiltration in PIT1-lineage PitNETs, compared with the TPIT-lineage, SF1-lineage subsets and NPs. While CD68 + macrophage, CD4 + T cells, and CD8 + T cells were not different among them. Increased M2-macrophage infiltration was associated with tumor volume (p < 0.0001, r = 0.57) in PIT1-lineage PitNETs. Meanwhile, differentially expressed immune checkpoint molecules (PD-L1, PD1, and CTLA-4) were screened and validated in IHC cohorts. The results showed that PD-L1 was highly expressed in PIT1-lineage subsets, and PD-L1 overexpression showed a positive correlation with tumor volume (p = 0.04, r = 0.29) and cavernous sinus invasion (p < 0.0001) in PIT1-lineage PitNETs. CONCLUSION: PIT1-lineage PitNETs exhibit a distinct immune profile with enrichment of M2 macrophage infiltration and PD-L1 expression, which may contribute to its clinical aggressiveness. Application of current immune checkpoint inhibitors and M2-targeted immunotherapy might be more beneficial to treat aggressive and metastatic PIT-lineage PitNETs.