Optimizing Large-Scale Educational Assessment with a "Divide-and-Conquer" Strategy: Fast and Efficient Distributed Bayesian Inference in IRT Models.

With the growing attention on large-scale educational testing and assessment, the ability to process substantial volumes of response data becomes crucial. Current estimation methods within item response theory (IRT), despite their high precision, often pose considerable computational burdens with large-scale data, leading to reduced computational speed. This study introduces a novel "divide- and-conquer" parallel algorithm built on the Wasserstein posterior approximation concept, aiming to enhance computational speed while maintaining accurate parameter estimation. This algorithm enables drawing parameters from segmented data subsets in parallel, followed by an amalgamation of these parameters via Wasserstein posterior approximation. Theoretical support for the algorithm is established through asymptotic optimality under certain regularity assumptions. Practical validation is demonstrated using real-world data from the Programme for International Student Assessment. Ultimately, this research proposes a transformative approach to managing educational big data, offering a scalable, efficient, and precise alternative that promises to redefine traditional practices in educational assessments.

Transferrin receptor levels and its rare variant are associated with human obesity.

AIM: Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown. METHODS: To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon-sequencing and genetic assessments were conducted of a case-control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole-exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis. RESULTS: TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild-type. CONCLUSIONS: Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.

A fluorinated peptide with high serum- and lipid-tolerence for the delivery of siRNA drugs to treat obesity and metabolic dysfunction.

Obesity is the major risk factor for metabolic diseases such as fatty liver, hyperlipidemia and insulin resistance. Beige fat has been recognized as a therapeutic target considering its great potential to burn energy. Since the evolutionary discovery of RNA interference and its utilization for gene knockdown in mammalian cells, a remarkable progress has been achieved in siRNA-based therapeutics. However, efficient delivery of siRNA into adipose tissues or differentiated adipocytes is challenging due to high lipid contents in these tissues. Here, we discovered a highly efficient fluoropolypeptide with excellent serum and lipid tolerance for this purpose from a library of amphiphlic polypeptides. The lead material F13-16 exhibited high gene knockdown efficacies in undifferentiated preadipocytes and differentiated adipocytes, as well as adipose tissues. It successfully delivered a siRNA targeting Tle3, an established suppressor gene for energy expenditure, in beige fat, and thereby ameliorated diet-induced obesity and metabolic disorders by increasing energy expenditure and thermogenic capacity. The results demonstrated that fluoropolypeptide is a useful tool for the delivery of siRNA-based therapeutics into adipocyte/adipose tissues for gene therapy.

A Designed Lithiophilic Carbon Channel on Separator to Regulate Lithium Deposition Behavior.

Issues with unstable SEI formation and uncontrollable lithium dendrite growth impede the practical use of lithium anode in high-energy batteries. Herein, a lithiophilic carbon channel on separator is designed to regulate lithium deposition behavior. The designed channel is formed by carbon nanosheet with cubic cavity (CNCC) prepared by hard template method. The CNCC with a large specific surface area and good electrolyte wettability can effectively reduce the local current density. Besides, the CNCC coated separator with high Young's modulus can mechanically inhibit the growth of lithium dendrites. Notably, CNCC coating can become lithiophilic during lithium plating/striping process, which is beneficial for homogeneous lithium deposition and low lithium nucleation overpotential. As a result, based on the CNCC coated separator, the symmetric Li|Li cell cycle over 2600h at 6 mA cm-2 for 2 mAh cm-2 , while the Li|Cu cell reaches average Coulombic efficiency of 98.5% at 2 mA cm-2 for 2 mAh cm-2 .

An Antipulverization and High-Continuity Lithium Metal Anode for High-Energy Lithium Batteries.

Lithium metal is one of the most promising anode candidates for next-generation high-energy batteries. Nevertheless, lithium pulverization and associated loss of electrical contact remain significant challenges. Here, an antipulverization and high-continuity lithium metal anode comprising a small number of solid-state electrolyte (SSE) nanoparticles as conformal/sacrificial fillers and a copper (Cu) foil as the supporting current collector is reported. Guiding by the SSE, this new anode facilitates lithium nucleation, contributing to form a roundly shaped, micro-sized, and dendrite-free electrode during cycling, which effectively mitigates the lithium dendrite growth. The embedded Cu current collector in the hybrid anode not only reinforces the mechanical strength but also improves the efficient charge transfer among active lithium filaments, affording good electrode structural integrity and electrical continuity. As a result, this antipulverization and high-continuity lithium anode delivers a high average Coulombic efficiency of ≈99.6% for 300 cycles under a current density of 1 mA cm-2 . Lithium-sulfur batteries (elemental sulfur or sulfurized polyacrylonitrile cathodes) equipped with this anode show high-capacity retentions in their corresponding ether-based or carbonate-based electrolytes, respectively. This new electrode provides important insight into the design of electrodes that may experience large volume variation during operations.

Transferrin Receptor Functionally Marks Thermogenic Adipocytes.

BACKGROUND: Thermogenic adipocytes, including beige and brown adipocytes, are critical for thermogenesis and energy homeostasis. Identification of functional cell surface markers of thermogenic adipocytes is of significance for potential application in biological and clinical practices. METHODS: With a combination of RNA-sequencing of in vivo and in vitro models, we identified transferrin receptor (Tfr1), a receptor specialized for cellular iron uptake, as a previously unappreciated cell surface molecule for thermogenic adipocytes compared to white adipocytes. The alternation of Tfr1 levels under physiological and pathological stimuli was assessed, and the mitochondria functionality, browning capacity, and iron metabolism of mature adipocytes were examined with Tfr1 knockdown. RESULTS: Tfr1 was expressed predominantly in thermogenic adipocytes versus white adipocyte, and its expression levels were tightly correlated with the activation or inhibition status of thermogenic adipocytes under external stimuli. Besides, Tfr1 gene deficiency in thermogenic adipocytes led to reduced thermogenic gene programs and mitochondrial integrity. CONCLUSION: Tfr1 functionally marks thermogenic adipocytes and could serve as a potential thermogenic adipocyte surface marker.

Comprehensive analysis of circular RNA profiles in skeletal muscles of aging mice and after aerobic exercise intervention.

Aging induces gradual accumulation of damages in cells and tissues, which leads to physiological dysfunctions. Aging-associated muscle dysfunction is commonly seen in aged population and severely affects their physical activity and life quality, against which aerobic training has been shown to exert antagonizing or alleviating effects. Circular RNAs (circRNAs) play important roles in various physiological processes, yet their involvement in aging-associated muscle dysfunction is not well understood. In this study, we performed comprehensive analysis of circRNAs profiles in quadriceps muscles in sedentary young and aging mice, as well as aging mice with aerobic exercise using RNA sequencing. Our results identified circRNAs altered by factors of aging and aerobic exercise. Their host genes were then predicted and analyzed by gene ontology enrichment analysis. Importantly, we found that circBBS9 featured decreased levels in aging compared to young mice and elevated expression in exercise versus sedentary aging mice. Besides, we performed GO and KEGG analysis on circBBS9 target genes, as well as established the circBBS9-miRNA-mRNAs interaction network. Our results indicate that circBBS9 may play active roles in muscle aging by mediating the benefits of aerobic training intervention, thus may serve as a novel therapeutic target combating aging-associated muscle dysfunction.

Designing Realizable and Scalable Techniques for Practical Lithium Sulfur Batteries: A Perspective.

To progress from the coin lithium sulfur (Li-S) cell to practical applications, it would be necessary to investigate industrially scalable methods to produce high-quality and large quantities of Li-S configurations. In this Perspective, we focused on the feasibility of scalable production of high-quality and large quantities of cathode composite, the construction of highly safe and highly stable electrolyte, and durable lithium metal anode. The results presented here suggest that the construction of highly secondary microstructures from nanoparticles is the key solution to achieve scalable cathode composite. Developing unconventional electrolyte solvent is a meaningful approach to develop high safety Li-S batteries. The high performance and high stability of lithium metal anode will enlighten the practical application of Li-S batteries. This Perspective presents outlooks for the key scalable techniques of realizable Li-S cell in the near future and provides promising strategies to accomplish long-cycle-life, high-energy-density Li-S batteries.

Role of Wnt/ß-catenin, Wnt/c-Jun N-terminal kinase and Wnt/Ca2+ pathways in cisplatin-induced chemoresistance in ovarian cancer.

The aim of the present study was to explore the expression of Wnt signaling proteins ß-catenin, c-Jun N-terminal kinase (JNK) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in ovarian cancer cells, and assess the correlation between this expression and cisplatin-induced chemoresistance. SKOV3 ovarian carcinoma cells and SKOV3/DDP (cisplatin resistant) cells were treated with cisplatin in the absence or presence of a Wnt signaling activator (CHIR-99021, glycogen synthase kinase 3ß inhibitor) or inhibitor (XAV-939, tankyrase inhibitor). Following incubation for 48 h, cell viability, proliferation and cytotoxicity were measured using a sensitive colorimetric cell counting kit. Expression levels of ß-catenin, JNK and CaMKII were detected by western blot and immunofluorescence staining. The results of the current study identified that ß-catenin and JNK expression levels were significantly higher (P<0.01 and P<0.05 respectively), while CaMKII expression was lower (P>0.05), in SKOV3/DDP cells compared with SKOV3 cells. Moreover, following treatment with 20 µM cisplatin, reduced expression of ß-catenin and JNK (P<0.05 and P<0.01 respectively), and increased expression of CaMKII (P<0.01), was observed in SKOV3 and SKOV3/DPP cell lines. Furthermore, inhibition of ß-catenin signaling by XAV-939 effectively reversed cisplatin chemoresistance in SKOV3/DDP cells. Similarly, XAV-939 downregulated JNK expression (P<0.001), but upregulated CaMKII expression (P<0.001), in SKOV3/DDP cells. In conclusion, abnormal activation of Wnt/ß-catenin and Wnt/JNK signaling pathways in ovarian cancer cells promotes cisplatin resistance, while the Wnt/Ca2+ signaling pathway reduces cisplatin resistance. This indicates that ß-catenin, JNK and CaMKII are potential therapeutic targets in chemoresistant ovarian cancers.

Cost-effectiveness analysis of neonatal hearing screening program in China: should universal screening be prioritized?

BACKGROUND: Neonatal hearing screening (NHS) has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China. METHODS: A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs), average cost-effectiveness ratio (ACER), and incremental cost-effectiveness ratio (ICER) for universal screening compared to targeted screening in eight provinces. RESULTS AND DISCUSSION: A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This study also showed that both strategies especially universal strategy achieve a good economic effect in the long term costs. CONCLUSIONS: Universal screening might be considered as the prioritized implementation goal especially in those relatively developed provinces of China as it provides the best health and economic effects, while targeted screening might be temporarily more realistic than universal screening in those relatively developing provinces of China.

[Erythromycin effects on apoptosis of epithelial cell in nasal polyps].

OBJECTIVE: To study the effect of erythromycin on apoptosis in epithelial cell and investigate the significance of epithelial cell apoptosis in nasal polyps forming. METHOD: Epithelial cell collected from thirty nasal polyps and six inferior turbinates were cultured in Dulbecco Eagle and Ham F12 (1:1) and divided into two groups, one cultured with Erythromycin(Erythromycin group), another cultured without Erythromycin (control group). Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. RESULT: The AI (apoptosis index) of epithelial cell in nasal polyps after cultured for 1,3,5 days with erythromycin were respectively (33.23 +/- 6.50)%, (38.21 +/- 7.22)% and (52.63 +/- 7.86)%. The AI of epithelial cell in inferior turbinates were respectively (31.02 +/- 5.60)%, (32.13 +/- 7.15)% and (39.64 +/- 7.48)%. There were significant difference between two groups at 5 day after culture (P < 0.05). CONCLUSION: Erythromycin promoted apoptosis of epithelial cell in nasal polyps.

[Effect of erythromycin on apoptosis of epithelial cell in nasal polyps].

OBJECTIVE: To study the effect of erythromycin on apoptosis and expression of Bax and Bcl-2 of epithelial cell in nasal polyps. METHODS: Epithelial cells from thirty nasal polyps and fifteen inferior turbinates were cultured in Dulbecco Eagle and Ham F12 (1:1) and divided into two groups (one group were treated with Erythromycin). Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling and expression of Bcl-2 and Bax detected by immunohistochemistry at 1, 3, 5 days after culture. RESULTS: The apoptosis indexes (AI) of epithelial cell in nasal polyps after cultured for 1, 3, 5 days with erythromycin were (33.23 +/- 6.50)%, (38.21 +/- 7.22)% and (52.63 +/- 7.86)% respectively. The AI of epithelial cell in inferior turbinates were (31.02 +/- 5.60)%, (32.13 +/- 7.15)% and (39.64 +/- 7.48)% respectively. There was significant difference between two groups at 5 day after culture (P < 0.05). Expression of Bax and Bcl-2 of epithelial cell was significantly higher in nasal polyps than that in inferior turbinates (P < 0.01). Expression of Bax of epithelial cell cultured with erythromycin was significantly higher than that in the controls (P < 0.05). Apoptosis was clearly promoted after 5 day culture with Erythromycin (P < 0.05). CONCLUSIONS: Erythromycin promoted expression of Bax and apoptosis of epithelial cell in nasal polyps.