InR and Pi3K maintain intestinal homeostasis through STAT/EGFR and Notch signaling in enteroblasts.

To maintain the integrity of the adult gut, the proliferation and differentiation of stem cells must be strictly controlled. Several signaling pathways control the proliferation and differentiation of Drosophila intestinal epithelial cells. Although the modulatory effects of insulin pathway components on cell proliferation have been characterized, their specific role in which cell type and how these components interact with other regulatory signaling pathways remain largely unclear. In this study, we found that InR/Pi3K has major functions in enteroblasts (EBs) that were not previously described. The absence of InR/Pi3K in progenitors leads to a decrease in the number of EBs, while it has no significant effect on intestinal stem cells (ISCs). In addition, we found that InR/Pi3K regulates Notch activity in ISCs and EBs in an opposite way. This is also the reason for the decrease in EB. On the one hand, aberrantly low levels of Notch signaling in ISCs inhibit their proper differentiation into EBs; on the other hand, the higher Notch levels in EBs promote their excessive differentiation into enterocytes (ECs), leading to marked increases in abnormal ECs and decreased proliferation. Moreover, we found that Upd/JAK/STAT signaling acts as an effector or modifier of InR/Pi3K function in the midgut and cooperates with EGFR signaling to regulate cell proliferation. Altogether, our results demonstrate that InR and Pi3K are essential for coordinating stem cell differentiation and proliferation to maintain intestinal homeostasis.

TSFFM: Depression detection based on latent association of facial and body expressions.

Depression is a prevalent mental disorder worldwide. Early screening and treatment are crucial in preventing the progression of the illness. Existing emotion-based depression recognition methods primarily rely on facial expressions, while body expressions as a means of emotional expression have been overlooked. To aid in the identification of depression, we recruited 156 participants for an emotional stimulation experiment, gathering data on facial and body expressions. Our analysis revealed notable distinctions in facial and body expressions between the case group and the control group and a synergistic relationship between these variables. Hence, we propose a two-stream feature fusion model (TSFFM) that integrates facial and body features. The central component of TSFFM is the Fusion and Extraction (FE) module. In contrast to conventional methods such as feature concatenation and decision fusion, our approach, FE, places a greater emphasis on in-depth analysis during the feature extraction and fusion processes. Firstly, within FE, we carry out local enhancement of facial and body features, employing an embedded attention mechanism, eliminating the need for original image segmentation and the use of multiple feature extractors. Secondly, FE conducts the extraction of temporal features to better capture the dynamic aspects of expression patterns. Finally, we retain and fuse informative data from different temporal and spatial features to support the ultimate decision. TSFFM achieves an Accuracy and F1-score of 0.896 and 0.896 on the depression emotional stimulus dataset, respectively. On the AVEC2014 dataset, TSFFM achieves MAE and RMSE values of 5.749 and 7.909, respectively. Furthermore, TSFFM has undergone testing on additional public datasets to showcase the effectiveness of the FE module.

Automatic recognition of depression based on audio and video: A review.

Depression is a common mental health disorder. With current depression detection methods, specialized physicians often engage in conversations and physiological examinations based on standardized scales as auxiliary measures for depression assessment. Non-biological markers-typically classified as verbal or non-verbal and deemed crucial evaluation criteria for depression-have not been effectively utilized. Specialized physicians usually require extensive training and experience to capture changes in these features. Advancements in deep learning technology have provided technical support for capturing non-biological markers. Several researchers have proposed automatic depression estimation (ADE) systems based on sounds and videos to assist physicians in capturing these features and conducting depression screening. This article summarizes commonly used public datasets and recent research on audio- and video-based ADE based on three perspectives: Datasets, deficiencies in existing research, and future development directions.

Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia.

Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce. We generated zebrafish models of IDH2R172K and IDH2R140Q AML and reported their pathologic, functional and transcriptomic features and therapeutic responses to target therapies. Transgenic embryos co-expressing FLT3ITD and IDH2 mutations showed accentuation of myelopoiesis. As these embryos were raised to adulthood, full-blown leukemia ensued with multi-lineage dysplasia, increase in myeloblasts and marrow cellularity and splenomegaly. The leukemia cells were transplantable into primary and secondary recipients and resulted in more aggressive disease. Tg(Runx1:FLT3ITDIDH2R172K) but not Tg(Runx1:FLT3ITDIDH2R140Q) zebrafish showed an increase in T-cell development at embryonic and adult stages. Single-cell transcriptomic analysis revealed increased myeloid skewing, differentiation blockade and enrichment of leukemia-associated gene signatures in both zebrafish models. Tg(Runx1:FLT3ITDIDH2R172K) but not Tg(Runx1:FLT3ITDIDH2R140Q) zebrafish showed an increase in interferon signals at the adult stage. Leukemic phenotypes in both zebrafish could be ameliorated by quizartinib and enasidenib. In conclusion, the zebrafish models of IDH2 mutated AML recapitulated the morphologic, clinical, functional and transcriptomic characteristics of human diseases, and provided the prototype for developing zebrafish leukemia models of other genotypes that would become a platform for high throughput drug screening.

B Lymphocyte Development in the Bursa of Fabricius of Young Broilers is Influenced by the Gut Microbiota.

Chickens have been used as a valuable and traditional model for studies on basic immunology. B lymphocytes were first identified in the bursa of Fabricius (BF) of broilers. The microbiota is important for immune system development and function. However, the effect of the microbiota on mediating B cell development and its regulatory mechanism is poorly elucidated. Here, we show that the gut microbiota is associated with the development of bursal B cells in young chickens. Changing patterns of both the alpha diversity and the expression of the B cell marker Bu-1α in the gut microbiota were related to the ages of chickens at different growth phases. Further correlation analysis revealed the marked correlation between the relative abundances of Intestinimonas, Bilophila, Parasutterella, Bacteroides, Helicobacter, Campylobacter, and Mucispirillum and the expression of Bu-1α. In antibiotic-treated chickens, BF and B cell development had aberrations as the relative abundance of the microbiota in early life decreased. These findings were consistent with Spearman's correlation results. Single-cell transcriptome analysis indicated that the heterogeneity in the cellular composition and developmental trajectory of bursal B cells from antibiotic-treated chickens was large. We found a novel subpopulation of unnamed B cells and identified Taf1 as a new pivotal regulator of B cell lineage differentiation. Therefore, we provide novel insights into the regulatory role of the gut microbiota in B cell development in early life and the maturation of host humoral immunity. IMPORTANCE In this study, we used young broilers to investigate the relationship between their gut microbiota and bursal B cell development. We characterized the important variables, microbes, B cells, and immunoglobulins during the posthatch development of birds. We also identified several candidate taxa in the cecal contents associated with B cells. Our study provides a rich resource and cell-cell cross talk model supporting B cell differentiation from the bursa in vitro at single-cell resolution. Furthermore, we determined a new pivotal regulator (Taf1) of B cell differentiation. We believe that our study makes a significant contribution to the literature because our findings may elucidate the role of the gut microbiota in B cell differentiation. This study also serves as a basis for developing new strategies that modulate B cell differentiation to prevent diseases.

Seismic Performance of Steel-Reinforced Concrete Columns with Q690 High-Strength Steel.

In this paper, based on the low-cycle loading tests of 11 steel-reinforced concrete (SRC) frame columns with built-in Q690 steel and 5 SRC frame columns with built-in Q235 steel, a systematic study on their seismic performance was carried out. The design parameters of the specimens were the steel strength, axial compression ratio, shear span ratio, steel content, and stirrup ratio. The failure modes, stress characteristics, hysteresis curve, skeleton curve, displacement ductility performance, energy dissipation capacity, and other main seismic indicators of the specimens with different parameters were analyzed, and the corresponding relationship between the displacement ductility performance of the specimen and the energy dissipation capacity and design parameters was obtained. The results show that the load-displacement curve of the specimens is relatively full, the descending section is gentle, and various seismic performance indicators are relatively excellent, reflecting good seismic performance. Equipped with high-strength steel SRC frame columns, they can better bear the horizontal load, the displacement ductility performance is improved, and the energy dissipation capacity is slightly lower than that of ordinary-strength steel SRC frame columns. The increase in the shear span ratio, steel content, and stirrup ratio of the specimens helps to improve their seismic performance, whereas an increase in the axial compression ratio makes their seismic performance worse.

The Investigation on Mechanical Performances of High-Strength Steel Reinforced Concrete Composite Short Columns under Axial Load.

At present, the existing standards (AISC360-16, EN1994-1-1:2004, and JGJ138-2016) lack relevant provisions for steel-reinforced concrete (SRC) composite columns with high-strength steel. To investigate the axial compressive mechanical performance of short high-strength steel-reinforced concrete (HSSRC) columns, the axial load test was conducted on 12 short composite columns with high-strength steel and ordinary steel. The influences of steel strength, steel ratio, and the section form of steel on the failure modes, bearing capacity, and ductility of the specimens were studied. Afterward, the experimental data were compared with the existing calculation results. The results show: compared with the specimens with Q235 steel, the bearing capacity of the specimens with Q460 steel increases by 7.8-15.3%, the bearing capacity of the specimens with Q690 steel increases by 13.2-24.1%, but the ductility coefficient increases by 15.2-202.4%; with the increase of steel ratio, the bearing capacity and ductility of specimens are significantly improved. A change of the steel cross-section could influence the ductility of SRC columns more than their bearing capacity. Moreover, the calculation results show that present standards could not predict the bearing capacity of HSSRC columns. Therefore, a modified method for determining the effective strength of steel equipped in HSSRC columns was proposed. The results of the ABAQUS simulation also showed that the addition of steel fibers could significantly improve the bearing capacity of Q690 HSSRC columns. The research results provide a reference for engineering practices.

Research on laser-assisted selective metallization of a 3D printed ceramic surface.

In recent years, the question of how to fabricate conductive patterns on complex ceramic surfaces in a high-definition and low-cost manner has been an increasing challenge. This paper presents a complete process chain for the selective metallization of Al2O3 ceramic surfaces based on 3D printing. Laser pre-activation (LPA) is used to "activate" the surface of the ceramic substrate, and then, combined with the electroless copper plating (ECP) process, the Al2O3 substrates can be metalized with preset patterns at room temperature, and a densely packed copper layer with high accuracy and good reproducibility can be obtained. The obtained coating has satisfactory roughness, excellent stability and bonding force, and good solderability. The resistivity of the copper layer measured using a four-probe resistance meter is about 3.1 mΩ cm. The limit line width of the metal circuit is about 33.2 µm. Finally, application cases of precision devices such as antennas with ceramic substrates are prepared. This study opens up a broader space for the design and manufacture of 3D microwave devices.

Identification of immune landscape signatures associated with clinical and prognostic features of hepatocellular carcinoma.

While cancer immunotherapy has been remarkably successful in some malignancies, some cancers derive limited benefit from current immunotherapies. Here, we combined immune landscape signatures with hepatocellular carcinoma clinical and prognostic features to classify them into distinct subtypes. The immunogenomic profiles, stromal cell features and immune cell composition of the subtypes were then systematically analyzed. Two independent prognostic indexes were established based on 6 immune-related genes and 17 differentially expressed genes associated with stromal cell content. These indexes were significantly correlated with tumor mutation burden, deficient DNA mismatch repair and microsatellite instability. In addition, tumor-infiltrating lymphocytes, including activated NK cells, resting memory CD4 T-cells, eosinophils, and activated mast cells were significantly correlated with hepatocellular carcinoma survival. In conclusion, we have comprehensively described the immune landscape signatures and identified prognostic immune-associated biomarkers of hepatocellular carcinoma. Our findings highlight potential novel avenues for improving responses to immunotherapy.

Nature of charge transport and p-electron ferromagnetism in nitrogen-doped ZrO2: an ab initio perspective.

Zirconium dioxide provides an exceptional prototype material for studying the redistribution of the polaron holes and its magnetic coupling with their nearby anions owning to the difference oxygen binding behavior in the monoclinic phase. Here, we perform a comprehensive study of the p-electron magnetism in the nitrogen doped 2 × 2 × 2 monoclinic ZrO2 based on spin-polarized density functional theory. Nitrogen substitutions make the system display half-metallic properties, and the origin of room temperature ferromagnetism ascribes to the p-p coupling interaction between N 2p and the host 2p states. The charge density difference and Mülliken population analyses provide evidences of charge redistributions. Our results reveal that the polaron transfer may alter the magnetic properties and it is greatly facilitated ferromagnetic coupling if the polaron holes are localized around a single anion dopant.