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Studies have shown that course participation and academic performance are key factors in defining the success of online education, but much remains unknown regarding how best to define the success of online K-12 after-school education that are popular in Asian countries. To address this issue, we used a longitudinal clustering approach to analyze the course records of a large online education company in China. In total, we analyzed data on 166 online English courses offered by a Chinese K12 after-school education company for the entire fall semester, and after excluding data on 10 classes where there were consecutive missing courses, the remaining 156 classes covered more than 200,000 primary school students enrolled in grades 1-6 in public schools. The results showed that there were two different patterns: classes with poor learning outcomes generally had high participation rates, while classes with good learning outcomes generally had low participation rates. Further analysis revealed that teacher's teaching experience, the difficulty of the course, and students' grade level helped explain the dichotomy. This finding shows that there can be dissociation between participation and achievement at the class level in online K-12 after-school education, which likely resulted from misalignment between requirements set by the course and the expectations from teachers and parents. This study provides important insight for future research and practice in online K-12 after-school education.

Background Study: Virtual reality (VR) is becoming a popular technology for safety training in construction. Several VR training prototypes have been designed and tested, which show they can perform better than traditional training tools. However, most of these existing tools are not underpinned by clear pedagogical theory, and studies assessing the impact of pedagogical theories on the effectiveness of VR prototypes are still rare in the literature. Objectives: This study aims to investigate if and how the productive failure theory and the directive instruction theory have an impact on the effectiveness of VR safety training for confined space workers. Methods: The study used a randomized controlled method involving 74 participants. The effectiveness of these two training methods was assessed in terms of knowledge acquisition and retention. Results and Conclusions: The results illustrate that the productive failure training design performed better in terms of knowledge acquisition and retention. This paper introduces the Productive Failure Theory and shows the great potential of this approach for self-service VR safety training in the field of construction.

Societal Impact Statement Nitrogen, phosphorus, and potassium are essential elements for plant growth and are the primary nutrients in commercial fertilizers. However, the extent to which these nutrients individually limit plant growth is still unclear, as is the influence of their interactions. Using a meta‐analysis approach, plant growth was found to be co‐limited by nitrogen, phosphorus, and potassium. Furthermore, these findings demonstrate that multiple nutrient additions are primarily additive, with the exception of synergistic effects observed with NP additions on plant growth. These findings are important as they provide a timely and valuable reference for assessing the ecosystem‐scale consequences of increasing nutrient deposition caused by human activities. Summary Numerous field studies and a few meta‐analyses have confirmed that terrestrial primary production is individually or jointly limited by nitrogen (N) and phosphorus (P). Meanwhile, a recent synthesis emphasized that potassium (K) limitation in terrestrial ecosystems is more widespread than previously thought. However, it remains unclear whether N, P, and K co‐limit terrestrial production and how their interactions influence plant growth. Therefore, we conducted a globally comprehensive synthesis of a total 2877 observations to explore the individual and interactive effects of N, P, and K additions on plant growth. We found that N, P, K, NP, NK, PK, and NPK additions significantly increased aboveground biomass production (AGP) by 30.8%, 15.3%, 12.3%, 68.4%, 36.5%, 21.1%, and 78.7%, respectively. The combined addition of multiple nutrients resulted in a larger increase in AGP than a single addition of nutrients. These findings suggested that terrestrial production is widely co‐limited by N, P, and K. However, no significant responses of belowground biomass production (BGP) to nutrient additions were observed. Except for synergistic interactions between N and P additions, the responses of AGP to other pairs of nutrient additions were predominantly additive. This meta‐analysis highlights the importance of multiple‐nutrient limitation in regulating terrestrial primary production while pointing out that non‐additive effects (including synergistic and antagonistic) of multiple‐nutrient additions on terrestrial production are relatively rare.

Aims: This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods: We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. Results: AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. Conclusion: The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management. Cite this article: Bone Joint Res 2024;13(10):525–534.

Aims: The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. Methods: A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated. Results: Escherichia coli was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated E. coli from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups. Conclusion: IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use. Cite this article: Bone Joint Res 2024;13(10):546–558.

Abstract Purpose To develop and validate a radiomic model for differentiating pulmonary invasive adenocarcinomas from benign lesions based on follow-up longitudinal CT images. Methods This is a retrospective study including 336 patients (161 with invasive adenocarcinomas and 175 with benign lesions) who underwent baseline (T0) and follow-up (T1) CT scans from January 2016 to June 2022. The patients were randomized in a 7:3 ratio into training and test sets. Radiomic features were extracted from lesion volumes of interest on longitudinal CT images at T0 and T1. Differences in radiomic features between T1 and T0 were defined as delta-radiomic features. Logistic regression was used to build models based on clinicoradiological (CR), T0, T1, and delta radiomic features and compute signatures. Finally, a nomogram based on the CR, T0, T1 and delta signatures was constructed. Model performance was evaluated for calibration, discrimination, and clinical utility. Results The T1 radiomic model was superior to the other independent models. In the training set, it had an area under the curve (AUC) of 0.858), superior to the CR model (AUC 0.694), the T0 radiomic model (AUC 0.825), and the delta radiomic model (AUC 0.734). In the test set, it had an AUC of 0.817, again outperforming the CR model (AUC 0.578), the T0 radiomic model (AUC 0.789), and the delta radiomic model (AUC 0.647). The nomogram incorporating the CR, T0, T1 and delta signatures showed the best predictive performance in both the training (AUC: 0.906) and test sets (AUC: 0.856), and it exhibited excellent fit with calibration curves. Decision curve analysis provided additional validation of the clinical utility of the nomogram. Conclusion A nomogram utilizing radiomic features extracted from longitudinal CT images can enhance the discriminative capability between pulmonary invasive adenocarcinomas and benign lesions.

Abstract The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand–receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, Stat6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.

Abstract Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Abstract Background Fusarium head blight (FHB), a devastating disease of wheat production, is predominantly elicited by Fusarium graminearum (Fg). The tetraploid Thinopyrum elongatum is a tertiary gene resource of common wheat that possesses high affinity and displays high resistance traits against multiple biotic and abiotic stress. We aim to employ and utilize the novel FHB resistance resources from the wild germplasm of common wheat for breeding. Results Durum wheat-tetraploid Th. elongatum amphiploid 8801 was hybridized with common wheat cultivars SM482 and SM51, and the F5 generation was generated. We conducted cytogenetically in situ hybridization (ISH) technologies to select and confirm a genetically stable 7E(7D) substitution line K17-1069-5, which showed FHB expansion resistance in both field and greenhouse infection experiments and displayed no significant disadvantage in agronomic traits compared to their common wheat parents in the field. The F2 segregation populations (K17-1069-5 × SM830) showed that the 7E chromosome conferred dominant FHB resistance with dosage effect. We developed 19 SSR molecular markers specific to chromosome 7E, which could be conducted for genetic mapping and large breeding populations marker-assisted selection (MAS) during selection procedures in the future. We isolated a novel Fhb7 allele from the tetraploid Th. elongatum chromosome 7E (Chr7E) using homology-based cloning, which was designated as TTE7E-Fhb7. Conclusions In summary, our study developed a novel wheat-tetraploid Thinopyrum elongatum 7E(7D) K17-1069-5 substitution line which contains stable FHB resistance.

Abstract Background Gastroesophageal reflux disease (GERD) is among the most common complications of bariatric surgery. This study aimed to analyse the risk factors affecting the worsening of GERD symptoms after laparoscopic sleeve gastrectomy (LSG), and to establish and validate a related nomogram model. Methods The study recruited 236 participants and randomly divided them into training and validation sets in a ratio of 7:3. LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to construct the column line graphs. The performance of the nomogram was evaluated and validated by analyzing the area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results In this study, Lasso-logistic regression was applied to select 5 predictors from the relevant variables, which were body mass index (BMI), diabetes, hiatal hernia, GERD, and triglyceride levels. These 5 predictor variables constructed a model with moderate predictive power, with an area under the ROC curve of 0.779 for the training set and 0.796 for the validation set. Decision curve analysis showed that in external validation, if the risk thresholds were between 4 and 98% and 14–95%, then the nomogram can be applied to the clinic. Conclusions We have developed and validated a nomogram that effectively predicts the risk of worsening gastroesophageal reflux symptoms following LSG.

Abstract To analyze the risk factors of secondary Central nervous system infections (CNSIs) after craniotomy, and to establish an individualized predictive model for CNSIs risk. The independent risk factors were screened by univariate and multivariate logistic regression analysis. Logistic regression, naive bayes, random forest, light GBM and adaboost algorithms were used to establish predictive models for secondary CNSIs after craniotomy. The predictive model based on the Adaboost algorithm demonstrated superior prediction performance compared to the other four models. Under 5-fold cross validation, the accuracy was 0.80, the precision was 0.69, the recall was 0.85, the F1-score was 0.76, the area under the ROC curve was 0.897,and the average precision was 0.880. The top 5 variables of importance in Adaboost model were operation time, indwelling time of lumbar drainage tube, indwelling lumbar drainage tube during operation, indwelling epidural drainage tube during operation, and GCS score. In addition, Adaboost model with the best prediction performance was used for clinical verification, and the prediction results were compared with the actual occurrence of CNSIs after surgery. The results showed that the accuracy of Adaboost model in predicting CNSIs was 60%, the accuracy of Adaboost model in predicting non-CNSIS was 92%, and the overall prediction accuracy was 76%.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract Bract coloration is one of the key ornamental traits in Bougainvillea, yet research has predominantly focused on phenotypic color traits and pigment composition, with limited understanding of the molecular mechanisms underlying color formation. This gap hinders the improvement and innovation in bract coloration. To elucidate the regulatory mechanisms of bract coloration in Bougainvillea and to enhance the utilization of its germplasm resources, this study employed the Illumina Novaseq 6000 sequencing platform to conduct transcriptomic sequencing on 21 samples of bracts exhibiting seven distinct phenotypes. Comparative analysis against Nr, Pfam, EggNOG, GO, and KEGG databases annotated 90,279 unigenes. The highest annotation rates were achieved with the Nr (40.13%), GO (30.44%), and EggNOG (25.64%) databases. Among the species annotated, Beta vulgaris (20.08%) and Chenopodium quinoa (14.58%) shared the highest homology with Bougainvillea bract transcriptomes. WGCNA analysis identified 12 positively correlated tissue-specific modules, of which 2 are related to bract color formation. By comparing transcriptome data and genes within these specific modules against the KEGG database, a total of 321 unigenes associated with bract color formation in Bougainvillea were discovered. Among these, 220 unigenes are involved in anthocyanin synthesis, 43 unigenes are involved in betalain synthesis, 23 unigenes are annotated as Chlorophyll a-b binding protein genes, and 35 unigenes participate in carotenoid synthesis. Quantitative real-time PCR (qRT-PCR) validation of 16 differentially expressed genes (DEGs) including PAL2, CHS1, ANS, BZ1, 6GT, CDOPA5GT, ANR, CHS2, and DOPA, revealed significant expression differences among magenta, yellow, white, and cherry-colored bracts, suggesting their potential as candidate genes for bract color development. This study not only enriches the transcriptomic data of Bougainvillea but also identifies genes associated with bract coloration, providing a valuable theoretical basis for future gene cloning, genetic engineering, and breeding efforts in Bougainvillea.

Abstract Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.

Abstract Background Chimeric antigen receptor (CAR)-NK cell therapy has shown remarkable clinical efficacy and safety in the treatment of hematological malignancies. However, this efficacy was limited in solid tumors owing to hostile tumor microenvironment (TME). Radiotherapy is commonly used for solid tumors and proved to improve the TME. Therefore, the combination with radiotherapy would be a potential strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors. Methods Glypican-3 (GPC3) was used as a target antigen of CAR-NK cell for hepatocellular carcinoma (HCC). To promote migration towards HCC, CXCR2-armed CAR-NK92 cells targeting GPC3 were first developed, and their cytotoxic and migration activities towards HCC cells were evaluated. Next, the effects of irradiation on the anti-tumor activity of CAR-NK92 cells were assessed in vitro and in HCC-bearing NCG mice. Lastly, to demonstrate the potential mechanism mediating the sensitized effect of irradiation on CAR-NK cells, the differential gene expression profiles induced by irradiation were analyzed and the expression of some important ligands for the NK-cell activating receptors were further determined by qRT-PCR and flow cytometry. Results In this study, we developed CXCR2-armed GPC3-targeting CAR-NK92 cells that exhibited specific and potent killing activity against HCC cells and the enhanced migration towards HCC cells. Pretreating HCC cells with irradiation enhanced in vitro anti-HCC effect and migration activity of CXCR2-armed CAR-NK92 cells. We further found that only high-dose (8 Gy) but not low-dose (2 Gy) irradiation in one fraction could significantly enhanced in vivo anti-HCC activity of CXCR2-armed CAR-NK92 cells. Irradiation with 8 Gy significantly up-regulated the expression of NK cell-activating ligands on HCC cells. Conclusions Our results indicate the evidence that irradiation could efficiently enhance the anti-tumor effect of CAR-NK cells in solid tumor model. The combination with radiotherapy would be an attractive strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.

Abstract Ultrasound technology has been recognized as the mainstream approach for the identification of gas-liquid two-phase flow patterns, which holds great value in engineering domain. However, commercial rigid probes are bulky, limiting their adaptability to curved surfaces. Here, we propose a strategy for autonomous identification of flow patterns based on flexible ultrasound array and machine learning. The array features high-performance 1–3 piezoelectric composite material, stretchable serpentine wires, soft Eco-flex layers and a polydimethylsiloxane (PDMS) adhesive layer. The resulting ultrasound array exhibits excellent electromechanical characteristics and offers a large stretchability for an intimate interfacial contact to curved surface without the need of ultrasound coupling agents. We demonstrated that the flexible ultrasound array combined with machine learning can accurately identify gas-liquid two-phase flow patterns, in a circular pipeline. This work presents an effective tool for recognizing gas-liquid two-phase flow patterns, offering engineering opportunities in petroleum extraction and natural gas transportation.

Abstract To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a “non-desert” immune phenotype than those with an immune “desert” phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

Abstract Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P

Abstract Background Streptococcus pneumoniae (S. pneumoniae) is a major cause of morbidity and mortality in children worldwide, and its evolving serotype distribution and antibiotic resistance patterns are of global health concern. This meta-analysis aims to investigate the serotype distribution and antimicrobial resistance of S. pneumoniae after the introduction of pneumococcal conjugate vaccine 13-valent (PCV13) as a self-funded vaccine in Chinese pediatric populations. Methods We systematically reviewed studies published between 2017 and 2024 that focused on S. pneumoniae serotypes isolated from children under 14 years old in mainland China. Data sources included PubMed, Embase, Web of Science, CNKI, Wanfang, and SinoMed. The findings were synthesized using either a fixed-effects or random-effects model. Results Our meta-analysis included 12 studies, identifying the most common serotypes of S. pneumoniae were 19 F, 19 A, 23 F, 14, 6B and 6 A. Vaccine serotype coverage rates were 52.17% (95%CI: 44.91-59.42%) for PCV10, 74.77% (95%CI: 71.53-78.01%) for PCV13, 76.72% (95%CI: 75.37-78.07%) for PCV15 and 92.90% (95%CI: 92.09-93.71%) for PPSV23. Antimicrobial resistance was most pronounced for erythromycin at 93.73% (95%CI: 90.58-96.88%), followed by azithromycin, tetracycline, clindamycin, and sulfamethoxazole. Serotype prevalence and vaccine coverage varied regionally and by strain type. Conclusion The distribution of S. pneumoniae serotypes and their antibiotic resistance profiles in children under 14 years in mainland China have remained relatively stable post-PCV13 introduction as a self-funded vaccine. The results support continued use and possible expansion of PCV13 immunization and highlight the importance of ongoing surveillance and vaccine development to cover all prevalent serotypes in China.

Abstract Aryl hydrocarbon receptor (AhR) plays an important role in inflammation and immunity as a new therapeutic target for infectious disease and sepsis. Punicalagin (PUN) is a Chinese herbal monomer extract of pomegranate peel that has beneficial anti-inflammatory, antioxidant and anti-infective effects. However, whether PUN is a ligand of AhR, its effect on AhR expression, and its signaling pathway remain poorly understood. In this study, we found that PUN was a unique polyphenolic compound that upregulated AhR expression at the transcriptional level, and regulated the AhR nongenomic pathway. AhR expression in lipopolysaccharide-induced macrophages was upregulated by PUN in vitro and in vivo in a time- and dose-dependent manner. Using specific inhibitors and siRNA, induction of AhR by PUN depended on sequential phosphorylation of 90-kDa ribosomal S6 kinase (p90RSK), which was activated by the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-dependent protein kinase (PDK)1 pathways. PUN promoted p90RSK-mediated activator protein-1 (AP-1) activation. AhR knockout or inhibitors reversed suppression of interleukin (IL)-6 and IL-1β expression by PUN. PUN decreased Listeria load and increased macrophage survival via AhR upregulation. In conclusion, we identified PUN as a novel selective AhR modulator involved in AhR expression via the MEK/ERK and PDK1 pathways targeting p90RSK/AP-1 in inflammatory macrophages, which inhibited macrophage inflammation and promoted bactericidal activity.

Abstract Wheat leaf rust, caused by Puccinia triticina (Pt), remains a constant threat to wheat production worldwide. Deployment of race-specific leaf rust (Lr) resistance genes in wheat provides effective protection against leaf rust, but often leads to selective pressures that drive the rapid emergence of new virulent Pt isolates in nature. However, the molecular mechanisms underlying the evasion of Lr-delivered resistance by leaf rust remain largely unknown. Here, we identify an avirulence gene AvrLr21 in Pt that triggers Lr21-dependent immune responses. BSMV (Barley stripe mosaic virus)-mediated host-induced gene silencing assay shows that silencing AvrLr21 compromises Lr21-mediated immunity. AvrLr21 interacts directly with Lr21 protein to induce a hypersensitive response in tobacco leaves. The evolved Lr21-breaking Pt isolates can suppress Lr21-mediated immunity. Our data provide a basis for studying the molecular determinants in Pt-wheat incompatible interaction and monitoring natural Pt populations to prioritize the deployment of Lr resistance genes in the field.

Abstract Background The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6–18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. Methods We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6–18. All persons were studied after obtaining informed consent from children and their parents. Results The mean FeNO50 of 5949 Chinese children and adolescents aged 6–18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6–11 age group, age and height were correlated with the logarithm of FeNO50 (P 0.05). The logarithm of CaNO was correlated with gender (P

Deterministically achieving on-chip photon storage and retrieval is a fundamental challenge for integrated photonics. Moreover, this requirement is increasingly urgent as photon storage and retrieval is crucial to realize truly scalable room-temperature quantum computing. However, most of existing quantum memories integrated on chips must either work at cryogenic temperature or else are strongly coupled with the environment, which hugely reduces the efficiency. Here, we propose an on-chip room-temperature quantum memory comprising three coupled microcavities, which presents an ideal dark state decoupled by a waveguide, thereby allowing on-demand photon storage and retrieval with high efficiency and high fidelity simultaneously. Furthermore, we demonstrate that the single-photon temporal duration can be increased or decreased by a factor of 103, thereby enabling many crucial quantum applications. Our error-robust approach highlights the potential for a solid-state photonic molecule for use as on-chip quantum memory and for optical quantum computing.

Abstract The growing prevalence of mental health issues underscores the need for innovative screening methods. Large-scale, internet-based psychological screening has emerged as a vital tool to accurately determine morbidity rates and facilitate early diagnosis of mental disorders. However, conventional psychological screening methods often struggle with non-genuine responses and lack objective metrics. To bridge this gap, we have compiled a novel dataset derived from an expansive screening initiative at Xinxiang Medical University. The study, conducted from February 27 to March 17, 2021, yielded a dataset comprising responses from 24,292 students to four well-established psychological scales—PHQ-9, GAD-7, ISI, and PSS. A distinctive feature of this dataset is the inclusion of response time data, which captures the temporal dynamics of participants’ interactions with the scales, offering valuable insights into their response behaviour. The release of this dataset offers a substantial opportunity for researchers in the domains of psychology and public health to explore new insights into mental health, scale reliability, and the dynamics of psychological assessment.

Abstract Uterine arteriovenous malformation (UAM) is a rare medical condition. Even though UAM can cause abnormal and life-threatening uterine hemorrhage, there is no consensus on the clinical guideline on its treatments, most likely due to its low incidence, unknown etiology, and distinct fertility demands by different patients. Here, we present one elderly woman with uncommon UAM. We first discuss our experience regarding the diagnoses and treatments of UAM and then propose a hypothesis for the pathogenesis of UAM.

Abstract Purpose The purpose of this study was to investigate whether the vastus medialis oblique (VMO) muscle compensates in patellar dislocation (PD) patients with the increased femoral anteversion angle (FAA). Methods Between 2021 and 2024, we included 60 patients with recurrent PD (RPD group). Inclusion criteria were at least two episodes of PD, as well as complete CT scans of the knee and hip. Exclusion criteria included traumatic or habitual dislocation, previous knee surgery, etc. Of these patients, 30 with excessive FAA (≥ 30°) were assigned to the A group, and 30 without excessive FAA (

Abstract We investigate the parity-violating effects in primordial gravitational waves (GWs) due to null energy condition (NEC) violation in two very early universe scenarios: bounce-inflation and intermediate NEC violation during inflation. In both scenarios, we numerically solve the power spectra of parity-violating primordial GWs generated by coupling the background field and the spectator field with the Nieh-Yan term, respectively. We find that the background field can significantly enhance parity-violating effects at scales corresponding to the maximum of the GW power spectra. In contrast, the parity-violating effects produced by the spectator show significantly weaker observability even if the coupling constant is large. Therefore, in NEC-violating scenarios, the significant observable parity-violating effects in primordial GWs primarily arise from the physics directly related to NEC violation. This result highlights the potential of primordial GWs as crucial tools for exploring NEC-violating and parity-violating physics.

Abstract Background Black spot disease in tree peony caused by the fungal necrotroph A. alternata, is a primary limiting factor in the production of the tree peony. The intricate molecular mechanisms underlying the tree peony resistance to A. alternata have not been thoroughly investigated. Results The present study utilized high-throughput RNA sequencing (RNA-seq) technology to conduct global expression profiling, revealing an intricate network of genes implicated in the interaction between tree peony and A. alternata. RNA-Seq libraries were constructed from leaf samples and high-throughput sequenced using the BGISEQ-500 sequencing platform. Six distinct libraries were characterized. M1, M2 and M3 were derived from leaves that had undergone mock inoculation, while I1, I2 and I3 originated from leaves that had been inoculated with the pathogen. A range of 10.22–11.80 gigabases (Gb) of clean bases were generated, comprising 68,131,232 − 78,633,602 clean bases and 56,677 − 68,996 Unigenes. A grand total of 99,721 Unigenes were acquired, boasting a mean length of 1,266 base pairs. All these 99,721 Unigenes were annotated in various databases, including NR (Non-Redundant, 61.99%), NT (Nucleotide, 45.50%), SwissProt (46.32%), KEGG (Kyoto Encyclopedia of Genes and Genomes, 49.33%), KOG (clusters of euKaryotic Orthologous Groups, 50.18%), Pfam (Protein family, 47.16%), and GO (Gene Ontology, 34.86%). In total, 66,641 (66.83%) Unigenes had matches in at least one database. By conducting a comparative transcriptome analysis of the mock- and A. alternata-infected sample libraries, we found differentially expressed genes (DEGs) that are related to phytohormone signalling, pathogen recognition, active oxygen generation, and circadian rhythm regulation. Furthermore, multiple different kinds of transcription factors were identified. The expression levels of 10 selected genes were validated employing qRT-PCR (quantitative real-time PCR) to confirm RNA-Seq data. Conclusions A multitude of transcriptome sequences have been generated, thus offering a valuable genetic repository for further scholarly exploration on the immune mechanisms underlying the tree peony infected by A. alternata. While the expression of most DEGs increased, a few DEGs showed decreased expression.

Abstract Objective To evaluate the potential utility of 18F-FDG PET/CT to assess response to neoadjuvant immunochemotherapy in patients with resectable NSCLC, and the ability to screen patients who may benefit from neoadjuvant immunochemotherapy. Methods Fifty one resectable NSCLC (stage IA–IIIB) patients were analyzed, who received two-three cycles neoadjuvant immunochemotherapy.18F-FDG PET/CT was carried out at baseline(scan-1) and prior to radical resection(scan-2). SULmax, SULpeak, MTV, TLG, T/N ratio, ΔSULmax%,ΔSULpeak%, ΔMTV%, ΔTLG%,ΔT/N ratio% were calculated. 18F-FDG PET/CT responses were classified using PERCIST. We then compared the RECIST 1.1 and PERCIST criteria for response assessment.With surgical pathology of primary lesions as the gold standard, the correlation between metabolic parameters of 18F-FDG PET/CT and major pathologic response (MPR) was analyzed. All metabolic parameters were compared to treatment response and correlated to PFS and OS. Results In total of fifty one patients, MPR was achieved in 25(49%, 25/51) patients after neoadjuvant therapy. The metabolic parameters of Scan-1 were not correlated with MPR.The degree of pathological regression was negatively correlated with SULmax, SULpeak, MTV, TLG, T/N ratio of scan-2, and the percentage changes of the ΔSULmax%, ΔSULpeak%, ΔMTV%,ΔTLG%,ΔT/N ratio% after neoadjuvant therapy (p

Abstract Traditional Chinese medicine (TCM) is considered to be one of the most comprehensive and influential form of traditional medicine. It plays an important role in clinical treatment and adjuvant therapy for cancer. However, the complex composition of TCM presents challenges to the comprehensive and systematic understanding of its antitumor mechanisms, which hinders further development of TCM with antitumor effects. Omics technologies can immensely help in elucidating the mechanism of action of drugs. They utilize high-throughput sequencing and detection techniques to provide deeper insights into biological systems, revealing the intricate mechanisms through which TCM combats tumors. Multi-omics approaches can be used to elucidate the interrelationships among different omics layers by integrating data from various omics disciplines. By analyzing a large amount of data, these approaches further unravel the complex network of mechanisms underlying the antitumor effects of TCM and explain the mutual regulations across different molecular levels. In this study, we presented a comprehensive overview of the recent progress in single-omics and multi-omics research focused on elucidating the mechanisms underlying the antitumor effects of TCM. We discussed the significance of omics technologies in advancing research on the antitumor properties of TCM and also provided novel research perspectives and methodologies for further advancing this research field.

Abstract Acute type A aortic dissection (ATAAD) is a lethal pathological process within the aorta with high mortality and morbidity. T lymphocytes are perturbed and implicated in the clinical outcome of ATAAD, but the exact characteristics of T cell phenotype and its underlying mechanisms in ATAAD remain poorly understood. Here we report that CD4+ T cells from ATAAD patients presented with a hypofunctional phenotype that was correlated with poor outcomes. Whole transcriptome profiles showed that ferroptosis and lipid binding pathways were enriched in CD4+ T cells. Inhibiting ferroptosis or reducing intrinsic reactive oxygen species limited CD4+ T cell dysfunction. Mechanistically, CD36 was elevated in CD4+ T cells, whose blockade effectively alleviated palmitic acid-induced ferroptosis and CD4+ T cell hypofunction. Therefore, targeting the CD36-ferroptosis pathway to restore the functions of CD4+ T cells is a promising therapeutic strategy to improve clinical outcomes in ATAAD patients.

Abstract Background Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people’s main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg’s Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. Methods We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. Discussion The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. Trial registration Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

This study aimed to screen out the differential metabolites between Taigu yam and Tiegun yam by metabolomics approach, and determine differential markers for predicting different yam varieties through the east absolute shrinkage and selection operator (LASSO) regression method. Ultra-performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was employed to analyze metabolites in two types of yams. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to identify distinct metabolites in these two yam varieties. Additionally, the LASSO regression method was used to screen out differential markers and establish a prediction model for variety identification. The results showed that a total of 206 metabolites were identified in the two yams. PCA found that Taigu yam and Tiegun yam were clearly distinguished. OPLS-DA further screened out 56 differential metabolites. LASSO regression analysis was performed based on these differential metabolites, and five differential markers were obtained including ophiogenin 3-O-beta-L-rhamnopyranosyl-beta-D-glucopyranoside, aspartic acid, epicatechin gallate, schaftoside and gallocatechin. These differential markers were used to establish a LASSO regression prediction model for identification of Taigu yam and Tiegun yam varieties. Based on metabolomics and LASSO regression methods, this study identified differential markers between Taigu yam and Tiegun yam, constructed a prediction model to identify different yam varieties, and would provide new ideas for the identification of yam.

Abstract. Background:. Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors. Methods:. The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25–70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020. Results:. The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy. Conclusions:. We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Urban vegetation in China has changed substantially in recent decades due to rapid urbanization and dramatic climate change. Nevertheless, the spatial differentiation of greenness among major cities of China and its evolution process and drivers are still poorly understood. This study examined the spatial patterns of vegetation greenness across 289 cities in China in 2000, 2005, 2010, 2015, and 2018 by using spatial autocorrelation analysis on the Normalized Difference Vegetation Index (NDVI); then, the influencing factors were analyzed by using the optimal parameters-based geographical detector (OPGD) model and 18 natural and anthropogenic indicators. The findings demonstrated a noticeable rise in the overall greenness of the selected cities during 2000–2018. The cities in northwest China and east China exhibited the rapidest and slowest greening, respectively, among the six sub-regions. A significant positive spatial correlation was detected between the greenness of the 289 cities in different periods, but the correlation strength weakened over time. The hot and very hot spots in southern and eastern China gradually shifted to the southwest. While the spatial pattern of urban greenness in China is primarily influenced by wind speed (WS) and precipitation (PRE), the interaction between PRE and gross domestic product (GDP) has the highest explanatory power. The explanatory power of most natural factors decreased and, conversely, the influence of anthropogenic factors generally increased. These findings emphasize the variations in the influence strength of multiple factors on urban greenness pattern, which should be taken into account to understand and adapt to the changing urban ecosystem.

Turbine blades are mainly subjected to thermal stress and gradient centrifugal stress in operational conditions. The effects of centrifugal stress on the microstructural degradation of single crystal superalloys under a multiaxial stress state remain unclear. Here, the NiAlReRu component was exposed to high-speed rotation at 20,000 rpm and a high temperature of 1000 °C for 100 h. The analysis indicates that the centrifugal stress causes the distortion of dendrite stems and the aggregation of micropores. The centrifugal stress promotes the formation of interfacial dislocation networks, accompanied by more severe rafting of γ′ phases. These findings provide a comprehensive experimental understanding of the microstructural evolution under simulated turbine blade working conditions, which provides a reference for the subsequent tests under near-service conditions.

Precise classification of Light Detection and Ranging (LiDAR) point cloud is a fundamental process in various applications, such as land cover mapping, forestry management, and autonomous driving. Due to the lack of spectral information, the existing research on single wavelength LiDAR classification is limited. Spectral information from images could address this limitation, but data fusion suffers from varying illumination conditions and the registration problem. A novel multispectral LiDAR successfully obtains spatial and spectral information as a brand-new data type, namely, multispectral point cloud, thereby improving classification performance. However, spatial and spectral information of multispectral LiDAR has been processed separately in previous studies, thereby possibly limiting the classification performance of multispectral LiDAR. To explore the potential of this new data type, the current spatial–spectral classification framework for multispectral LiDAR that includes four steps: (1) neighborhood selection, (2) feature extraction and selection, (3) classification, and (4) label smoothing. Three novel highlights were proposed in this spatial – spectral classification framework. (1) We improved the popular eigen entropy-based neighborhood selection by spectral angle match to extract a more precise neighborhood. (2) We evaluated the importance of geometric and spectral features to compare their contributions and selected the most important features to reduce feature redundancy. (3) We conducted spatial label smoothing by a conditional random field, accounting for the spatial and spectral information of the neighborhood points. The proposed method demonstrated by a multispectral LiDAR with three channels: 466 nm (blue), 527 nm (green), and 628 nm (red). Experimental results demonstrate the effectiveness of the proposed spatial – spectral classification framework. Moreover, this research takes advantages of the complementation of spatial and spectral information, which could benefit more precise neighborhood selection, more effective features, and satisfactory refinement of classification result. Finally, this study could serve as an inspiration for future efficient spatial–spectral process for multispectral point cloud.

While well-being of school principals is becoming an increasing concern in public education, the understanding of well-being and its manifestation is still lacking in research. This research tackles the nuances and complexities surrounding the notion of well-being and sheds light on its conceptualisation, manifestation, and contributing factors. Data for this research come from an online survey among public school principals in the province of British Columbia, Canada. This survey research utilised reliability, factor, correlation analysis, and structural equation modelling (SEM) and examined how well-being of school principals is manifested along different well-being dimensions and what underlying relationships exist between each dimension in relation to principals' overall well-being and their demographics. The results reaffirm that well-being is a multidimensional construct, encompassing dimensions that speak to different but interrelated aspects of a principal's well-being state, among which emotional and psychological well-being has been revealed as a vital component in principals' overall well-being. The findings have significant implications on health and well-being related support for school principals in order to prepare them for the increasingly demanding job.