Search

Pod size is a key agronomic trait that influences peanut yield greatly. However, our understanding of the mechanisms underlying pod size is limited. In this study, we employed a segregating population derived from a cross between the small-pod line ND_S and the large-pod line ND_L to map quantitative trait loci (QTL) associated with pod size. Initial mapping performed using bulk segregant analysis revealed a candidate interval on chromosome A05 referred to as qPSW05. We refined this interval to a 256.9 kb genomic region using newly developed molecular markers. Through sequence and expression analyses, we identified the candidate gene AhXE45GC, which encodes an AN1 zinc finger protein. We discovered a 33-bp insertion in the intron of AhXE45GC in ND_S. Accessions that lack this insertion, such as ND_L, had significantly larger pods than those with the insertion, including ND_S. To facilitate marker-assisted selection for peanut pod size, we developed a molecular marker associated with this polymorphism. This marker could provide a valuable genetic resource for breeding high-yielding peanut varieties.

Indium (In) has been extensively used as a thermal interface material (TIM1) between the die and lid in high-power central processing units (CPUs) to enhance heat dissipation. However, organic flux residues trapped within the In solder during indium reflow process can outgas during subsequent solder ball reflow cycles, leading to the formation of significant voids (up to 35% void fraction) in the In TIM1. This issue limits the application of In in advanced ball grid array (BGA) packages. In this study, for the first time, varying thicknesses Ag coatings were electroplated onto the surfaces of thick In TIM1 to form a non-oxidizing AgIn2 layer (In@xAgIn2, where x = 0.4, 1, 3, 6 μm) to protects the inner In from oxidation and enables fluxless reflow. Joints prepared with In or In@xAgIn2 underwent indium reflow and three solder ball reflow cycles to simulate the reflow processes typical of BGA packages. A clear AgIn2 thickness effect on solder wettability, microstructure, intermetallic compound (IMC) growth, joint thermal and mechanical properties were found. The results showed that In@0.4AgIn₂; had a contact angle of 26.2°, which was 2.6° lower than that of pure In solder. Joints prepared with In@0.4AgIn₂; also exhibited the lowest void fraction (≤2%), which contributed to better heat dissipation. During reflow, the Ag atoms from the AgIn2 protective layer altered the morphology and reduced the thickness of the Ni3In7 IMC layer. After reflow, the Ag atoms either solubilized in In or formed AgIn2 IMC with distinct distribution characteristics in the solder layer, which increased the shear strength of the joints by 81.5%. The fracture mode of the joints also changed from ductile to ductile-brittle, and ultimately to brittle.

Peanut (Arachis hypogaea L.) is an important oil crop. Oleic acid is a major factor that determines the quality of peanuts. Therefore, the high oleic and high oleic to linoleic acid ratio are the target traits in an advanced peanut breeding program. This study provided an extensive evaluation of the genetic and physical characteristics as well as disease resistance of 220 high oleic peanut varieties in China. Notably, these varieties clustered into five major categories based on their traits. A majority of these varieties have been bred using interspecific hybridization or selected from mutants of self-crossed parents, with the main parent varieties being Kaixuan 016 and CTWE. Analysis of disease resistance showed that most high oleic peanut varieties could resist two or three diseases. However, those varieties with resistance to multiple diseases were relatively scarce. Moreover, some high oleic peanut varieties showed no disease resistance or inadequate testing. The results further indicate that the genetic basis for high oleic peanut breeding is insufficient, highlighting the need for its further development. Importantly, our findings lay a critical foundation for future high oleic peanut breeding and promote better understanding of the genetic and trait diversity offered by these varieties.

Abstract Purpose It is a central goal in current ecology to investigate the effects of global changes on ecosystem productivity, which includes above- and below-ground plant productivity as well as soil microbial productivity, but most studies focus on aboveground plant productivity. As plant and microbial communities have different attributes, it is intuitive to hypothesize that belowground plant root productivity will respond to global changes more similarly as aboveground stem/leaf productivity than soil microbial productivity; however, this hypothesis remains largely unexplored. Methods Here we conducted a long-term nitrogen deposition experiment in the Eurasian steppe, manipulating nine rates (0–50 g N m− 2 yr− 1) at two frequencies under two management strategies (fencing or mowing). Results Belowground plant productivity was found to respond similarly as soil microbial productivity rather than aboveground plant productivity, contrary to the hypothesis. And this pattern was more obvious under mowing than fencing, because mowing decreased soil water content and caused another pressure beyond the decreased pH induced by N addition. Conclusions Overall, our results demonstrated the importance of microhabitat (below- or above-ground) relative to community attribute (plants or microorganisms) in determining productivity response to nitrogen deposition, emphasizing the necessity to integratively study the response of both above- and below-ground productivities to global changes.

Supercritical lens (SCL) can break the diffraction limit in the far field and has been demonstrated for high-resolution scanning confocal imaging. Its capability in sharper focusing and needle-like long focal depth should allow high-resolution lithography at violet or ultraviolet (UV) wavelength, however, this has never been experimentally demonstrated. As a proof of concept, in this paper SCLs operating at 405 nm (h-line) wavelength with smaller full-width-at-half-maximum focal spot and longer depth of focus than conventional Fresnel zone lens while maintaining controlled side lobes are designed for direct laser writing (DLW) lithography. Aluminum nitride (AlN) with a high refractive index and low loss in UV-visible range is used to fabricate nanopillar-based metasurfaces structure for the metalens. Grating arrays with improved pitch resolution are fabricated using the SCLs with sub-diffraction-limit focusing capability. The AlN-based metasurface for SCLs at short wavelength for DLW could extend further to UV or deep UV lithography and might be of great interest to both the research and industry applications.

Abstract Background Protein–protein interactions are the primary means through which proteins carry out their functions. These interactions thus have crucial roles in life activities. The wide availability of fully sequenced animal and plant genomes has facilitated establishment of relatively complete global protein interaction networks for some model species. The genomes of cultivated and wild peanut (Arachis hypogaea L.) have also been sequenced, but the functions of most of the encoded proteins remain unclear. Results We here used homologous mapping of validated protein interaction data from model species to generate complete peanut protein interaction networks for A. hypogaea cv. ‘Tifrunner’ (282,619 pairs), A. hypogaea cv. ‘Shitouqi’ (256,441 pairs), A. monticola (440,470 pairs), A. duranensis (136,363 pairs), and A. ipaensis (172,813 pairs). A detailed analysis was conducted for a putative disease-resistance subnetwork in the Tifrunner network to identify candidate genes and validate functional interactions. The network suggested that DX2UEH and its interacting partners may participate in peanut resistance to bacterial wilt; this was preliminarily validated with overexpression experiments in peanut. Conclusion Our results provide valuable new information for future analyses of gene and protein functions and regulatory networks in peanut.

Abstract Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Aims To investigate the associations between influencing factors with length of stay (LOS) and hospitalisation expenses in oral cancer (OC) patients, and to explore the potential pathways through which these factors influence hospitalisation expenses using path analysis.Design Cross-sectional.Setting A comprehensive tertiary hospital in southeastern China.Participants A total of 810 patients with histologically confirmed primary OC admitted to the First Affiliated Hospital of Fujian Medical University, Fujian Province, between 2015 and 2020.Main outcome measures LOS and hospitalisation expenses for OC patients.Results The median hospitalisation expenses and LOS for OC patients in southeastern China were substantial, amounting to $6330 and 29 days, respectively. Treatment and surgery fees constituted the largest proportion of total expenses (28.59%), followed by inspection and laboratory test fees (20.63%), comprehensive medical service fees (19.27%), drug fees (18.09%) and medical consumables fees (11.69%). LOS was significantly associated with tumour site, surgery and chemotherapy. Factors such as longer LOS, poor oral hygiene, advanced tumour stage (II–IV), larger tumour size (>2 cm3), surgery and bilateral neck dissection were strongly linked to higher hospitalisation expenses. Path analysis revealed that neck dissection had the highest total effect on hospitalisation expenses (β=0.307), while surgery exerted an indirect effect on expenses via LOS (β=0.021).Conclusion This study highlights the significant economic burden imposed by OC on patients and healthcare systems. While prevention and early diagnosis remain critical, our findings underscore several modifiable factors, including improving oral hygiene and optimising surgical protocols, such as chemotherapy and lymph node dissection, that present opportunities to reduce costs and enhance cost-effectiveness. These insights provide actionable targets for mitigating financial burdens and improving patient outcomes.

Cherry eye, the common name for the prolapse of the third eyelid gland in dogs, is a widespread ophthalmic disease affecting dogs of various breeds. This condition severely affects the quality of life of affected dogs, and its underlying cause remains unresolved. In this study, 170K SNP microarray data were collected from 653 brachycephalic dogs and 788 brachycephalic and mesocephalic dogs. These two datasets were analyzed separately in genome-wide association studies (GWAS) involving 12 dog breeds affected by cherry eye. The GWAS analysis of 653 short-headed dogs revealed that four SNPs in the CFA3:15627075-15983629 bp region exceeded the genome-level significance threshold. Association analysis of this region also indicated that these four SNPs were strongly associated. Gene annotation showed that the region contained genes such as KIAA0825, FAM172A, and NR2F1, of which NR2F1 was associated with eye development. The results showed that GWAS analysis performed on 788 short- and medium-headed dogs identified five SNPs in the CFA22:15627075-15983629 bp region that exceeded the genome-level significance threshold, and association analysis was performed in this region, which showed that these five SNPs were strongly associated. In addition, 104 annotated genes were identified in both GWAS. To explore the genes involved in cherry eyes, we performed GO functional enrichment analysis. The genes involved in the high pathway were DIO3 and TTC8. In addition, an in-depth analysis revealed 33 genes associated with eye development and diseases. Our study provides new perspectives for further understanding cherry eye in dogs.

IntroductionTraditional Miao and Dai Chinese medicines have used nicotine-rich leaf tobacco to treat traumatic injuries by promoting hemostasis. While nicotine is known to enhance platelet aggregation, its effects on other platelet functions and underlying mechanisms remain unclear.Methods and ResultsThis study aimed to thoroughly investigate nicotine’s effects on human platelets and its pharmacological mechanisms, using thromboelastography to assess nicotine’s impact on platelet function during coagulation. This study aimed to investigate the functional effects of nicotine on human platelets and elucidate its pharmacological mechanisms. The impact of nicotine on platelet function during the coagulation process was assessed using thromboelastography. Further studies showed that nicotine fully activates washed platelets, promoting aggregation, granule release, adhesion, spreading, and plaque retraction. Concurrently, nicotine was found to enhance the intracellular concentration of calcium ions in platelets ([Ca2+]i). To explore the underlying mechanisms, molecular docking software was employed to identify the platelet membrane receptors PAR1 and PAR4, which exhibited the highest docking scores with nicotine. Intervention with two receptor inhibitors demonstrated that only the PAR4 inhibitor could reverse the stimulatory effects of nicotine on platelet granule release. Through the examination of alterations in the downstream signaling pathways of PAR4 receptors, it was determined that nicotine promo-facilitates the phosphorylation of PI3K, AKT, and ERK1/2 proteins, subsequently contributing to the activation of αIIbβ3 receptors in platelets. Conversely, the application of PAR4 inhibitors was found to reverse these effects.DiscussionIn conclusion, nicotine activates αIIbβ3 receptors and significantly enhances platelet function by promoting the phosphorylation of the platelet PAR4 receptor signaling pathway. These findings suggest the potential utility of nicotine as a hemostatic agent.

Abstract Background The determining effect of facial hard tissues on soft tissue morphology in orthodontic patients has yet to be explained. The aim of this study was to clarify the hard-soft tissue relationships of the lower 1/3 of the face in skeletal Class II-hyperdivergent patients compared with those in Class I-normodivergent patients using network analysis. Methods Fifty-two adult patients (42 females, 10 males; age, 26.58 ± 5.80 years) were divided into two groups: Group 1, 25 subjects, skeletal Class I normodivergent pattern with straight profile; Group 2, 27 subjects, skeletal Class II hyperdivergent pattern with convex profile. Pretreatment cone-beam computed tomography and three-dimensional facial scans were taken and superimposed, on which landmarks were identified manually, and their coordinate values were used for network analysis. Results (1) In sagittal direction, Group 2 correlations were generally weaker than Group 1. In both the vertical and sagittal directions of Group 1, the most influential hard tissue landmarks to soft tissues were located between the level of cemento-enamel junction of upper teeth and root apex of lower teeth. In Group 2, the hard tissue landmarks with the greatest influence in vertical direction were distributed more forward and downward than in Group 1. (2) In Group 1, all the correlations for vertical-hard tissue to sagittal-soft tissue position and sagittal-hard tissue to vertical-soft tissue position were positive. However, Group 2 correlations between vertical-hard tissue and sagittal-soft tissue positions were mostly negative. Between sagittal-hard tissue and vertical-soft tissue positions, Group 2 correlations were negative for mandible, and were positive for maxilla and teeth. Conclusion Compared with Class I normodivergent patients with straight profile, Class II hyperdivergent patients with convex profile had more variations in soft tissue morphology in sagittal direction. In vertical direction, the most relevant hard tissue landmarks on which soft tissue predictions should be based were distributed more forward and downward in Class II hyperdivergent patients with convex profile. Class II hyperdivergent pattern with convex profile was an imbalanced phenotype concerning sagittal and vertical positions of maxillofacial hard and soft tissues.

Objectives: Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of Fscn2 on cisplatin-induced hearing impairment in mice and to explore the possible mechanism. Methods: Two-week-old Fscn2+/+ mice and Fscn2−/− mice were treated with two doses of cisplatin, with a 3-day recovery period in between. ABR (auditory evoked brain stem response) thresholds were measured and cochlear pathology was observed at 3 weeks of age. Results: Both Fscn2+/+ and Fscn2−/− mice showed hearing loss under the effect of cisplatin, but the impairment was more severe in Fscn2−/− mice. Further experiments showed that the percentages of outer hair cell (OHC) and spiral ganglion neuron (SGN) loss were significantly higher in cisplatin-treated Fscn2−/− mice compared to Fscn2+/+ mice. Additionally, knockdown of Fscn2 in HEI-OC1 cells worsened cisplatin-induced cell apoptosis. Conclusion: FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis.

Abstract Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.

Abstract Background Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy. Methods We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike’s information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model’s performance. Results The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9. Conclusions Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

Abstract Background Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear. Methods We assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable. Conclusions This MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases.

Abstract Accurate predictions of monthly extremes assume paramount importance in enabling proactive decision‐making, which however are lacked in skills even for state‐of‐the‐art dynamical models. Taking the extreme precipitation prediction over the mid‐to‐lower reaches of the Yangtze River, China, as an instance, a multi‐predictor U‐Net deep learning approach is designed to enhance the prediction over the European Center for Medium‐Range Weather Forecasts (ECMWF) model, with the single‐predictor U‐Net parallelly examined as the benchmark. Focusing on the precipitation extremes, an extreme associated component is incorporated into the model loss function for optimization. Besides, predictions composed by daily outputs with multiple lead times are imported as a comprehensive set in the training phase to augment the deep learning sample size and to emphasize enhancements in predictions at the monthly timescale as a whole. Results indicate that the multi‐predictor U‐Net effectively improves predictions of extreme summer precipitation frequency, showing distinct superiority to the raw ECMWF and the single‐predictor U‐Net. Multiple evaluation metrics indicate that the model shows a significant positive improvement ratio ranging from 65.1% to 80.0% across all grids compared to the raw ECMWF prediction, which has also been validated through applications in the two extreme summer precipitation cases in 2016 and 2020. Besides, a ranking analysis of feature importance reveals that factors such as humidity and temperature play even more crucial roles than precipitation itself in the multi‐predictor extreme precipitation prediction model at the monthly timescale. That is, in such a deep learning approach, the monthly prediction on extreme precipitation benefits significantly from the inclusion of multiple associated predictors.

With the rapid growth of information flux, integrating more channels in limited spaces has been a critical requirement for highly-integrated long-range parallel transmissions. Although meta-waveguides, such as spoof surface plasmon polariton (SSPP) waveguides, can suppress crosstalk between adjacent channels, it is still urgent to seek new methods to further increase the number of channels without occupying additional space. Here, we propose a reconfigurable dual-mode meta-waveguide (RDMMW) by integrating diodes into meta-units, which supports two independent channels using two orthogonal modes. The RDMMW can be switched among dual-mode, even-mode, odd-mode and cutoff states by controlling the diodes, which provides more freedom to manipulate the channel features. The RDMMW possess two outstanding merits in highly-integrated long-range parallel transmissions, including lower coupling between two channels than conventional single-mode waveguides and constant mode coupling in longer waveguides. Thus the proposed RDMMW has advantages of multi-mode, reconfiguration, low coupling and high integration density, providing a new avenue to realize highly-integrated multi-functional systems.

ABSTRACT The microbiome of wild animals is believed to be co-evolved with host species, which may play an important role in host physiology. It has been hypothesized that the rigorous hygienic practices in combination with antibiotics and diets with simplified formulas used in the modern swine industry may negatively affect the establishment and development of the gut microbiome. In this study, we evaluated the fecal microbiome of 90 domestic pigs sampled from nine farms in Canada and 39 wild pigs sampled from three different locations on two continents (North America and Europe) using 16S rRNA gene amplicon sequencing. Surprisingly, the gut microbiome in domestic pigs exhibited higher alpha-diversity indices than wild pigs (P < 0.0001). The wild pig microbiome showed a lower Firmicutes-to-Bacteroidetes ratio and a higher presence of bacterial phyla Elusimicrobiota, Verrucomicrobiota, Cyanobacteria, and Fibrobacterota when compared to their domestic counterparts. At the genus level, the wild pig microbiome had enriched genera that were known for fiber degradation and short-chain fatty acid production. Interestingly, the phylum Fusobacteriota was only observed in domestic pigs. We identified 31 ASVs that were commonly found in the pig gut microbiome, regardless of host sources, which could be recognized as members of the core gut microbiome. Interestingly, we found five ASVs missing in domestic pigs that were prevalent in wild ones, whereas domestic pigs harbored 59 ASVs that were completely absent in wild pigs. The present study sheds light on the impact of domestication on the pig gut microbiome, including the gain of new genera, which might provide the basis to identify novel targets to manipulate the pig gut microbiome for improved health.IMPORTANCEThe microbiome of pigs plays a crucial role in shaping host physiology and health. This study sought to identify if domestication and current rearing practices have resulted in a loss of co-evolved bacterial species by comparing the microbiome of wild boar and conventionally raised pigs. It provides a comparison of domestic and wild pigs with the largest sample sizes and is the first to examine wild boars from multiple sites and continents. We were able to identify core microbiome members that were shared between wild and domestic populations, and on the contrary to expectation, few microbes were identified to be lost from wild boar. Nevertheless, the microbiome of wild boars had a lower abundance of important pathogenic genera and was distinct from domestic pigs. The differences in the microbial composition may identify an opportunity to shift the microbial community of domestic pigs towards that of wild boar with the intent to reduce pathogen load.

Bone defects are highly prevalent diseases caused by trauma, tumors, inflammation, congenital malformations and endocrine abnormalities. Ideally effective and side effect free approach to dealing with bone defects remains a clinical conundrum. Klotho is an important protein, which plays an essential role in regulating aging and mineral ion homeostasis. More recently, research revealed the function of Klotho in regulating skeleton development and regeneration. Klotho has been identified in mesenchymal stem cells, osteoblasts, osteocytes and osteoclasts in different skeleton regions. The specific function and regulatory mechanisms of Klotho in long bone and craniofacial bone vary due to their different embryonic development, ossification and cell types, which remain unclear and without conclusion. Moreover, studies have confirmed that Klotho is a multifunctional protein that can inhibit inflammation, resist cancer and regulate the endocrine system, which may further accentuate the potential of Klotho to be the ideal molecule in inducing bone restoration clinically. Besides, as an endogenous protein, Klotho has a promising potential for clinical therapy without side effects. In the current review, we summarized the specific function of Klotho in long bone and craniofacial skeleton from phenotype to cellular alternation and signaling pathway. Moreover, we illustrated the possible future clinical application for Klotho. Further research on Klotho might help to solve the existing clinical difficulties in bone healing and increase the life quality of patients with bone injury and the elderly.

By employing the classic system poly(3-hexylthiophene-2,5-diyl): [6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PC61BM), organic bulk heterojunction films were applied on an indium tin oxide substrate using a one-step spin-coating method, without requiring any complex manufacturing processes, to obtain self-powered photodetectors (PDs) with a simple preparation process. The fullerene material was introduced to create a bulk heterojunction film with proper phase separation and greatly enrich the donor/acceptor dissociation interface, thus improving the high exciton binding energy and short exciton diffusion distance. The built-in electric field formed by the Schottky junction at the interface between the active layer and electrode can enhance the separation of excitons and the transport of charge carriers, realizing optical detection without external energy sources. Moreover, femtosecond transient absorption was employed to investigate the exciton dynamics in organic films and analyze the working mechanism of self-powered detection performance. The long-lived behavior of carriers and the formation of charge transfer states were further verified, which contributed to the enhanced performance of the device. As a result, the self-powered PD-based Schottky bulk heterojunction presents a high light on/off ratio of over 104 (0 V) and fast response speed with rise and decay times of 33 and 36 µs, respectively, under a 532 nm light illumination. These results provide theoretical and experimental verification of this technique for the development of self-powered PDs in the field of organic materials.

This paper explores the significant role of epigenetics in women’s reproductive health, focusing on the impact of environmental factors. It highlights the crucial link between epigenetic modifications—such as DNA methylation and histones post-translational modifications—and reproductive health issues, including infertility and pregnancy complications. The paper reviews the influence of pollutants like PM2.5, heavy metals, and endocrine disruptors on gene expression through epigenetic mechanisms, emphasizing the need for understanding how dietary, lifestyle choices, and exposure to chemicals affect gene expression and reproductive health. Future research directions include deeper investigation into epigenetics in female reproductive health and leveraging gene editing to mitigate epigenetic changes for improving IVF success rates and managing reproductive disorders.

Understanding the coupling relationship between ecosystem service perceptions (ESP) and farmers’ well-being (FWB) in the ore-agriculture zone plays an important strategic role in maintaining regional ecological security and improving the well-being of regional farmers. Based on field research, questionnaire surveys and other methods, this study took farmers around the coal mining development zone as research subjects and used a comprehensive multi-index assessment method to evaluate the level of ESP and the FWB in the research area. A coupling coordination degree model was used to analyze the coupling relationship between ESP and FWB, and the random forest model was used to explore the influencing factors of the coupling relationship between the two. The results showed: (1) The FWB index was moderate and the ESP index was low. Farmers’ perceptions of the different ecosystem services varied, with provisioning services being perceived most strongly and supporting services least strongly. Satisfaction with basic material needs was highest on the well-being assessment. (2) The overall state of ESP and FWB coupling was good, with most of them in the state of coordination improvement. From the perspective of dimensional differentiation, the coupling of the dimensions of ESP and FWB was poorly coordinated, and all of them were in the state of dysfunction regression. (3) The coupling relationship between ESP and FWB was influenced by both environmental and household characteristics, with the former having a stronger effect. The results of this study can serve as a reference for promoting the coordination of ESP and FWB in the ore-agriculture zone, and ultimately realize the sustainable development of ecology and human in the ore-agriculture zone.

Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments for control of infectious disease, notably their pivotal role in combating the COVID-19 pandemic. This review focuses on fundamental aspects of the development of mRNA vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, – highlighting key technological advances. The recent, promising success of personalized mRNA vaccines against pancreatic cancer and melanoma illustrates the potential value for other intractable, immunologically resistant, solid tumors, such as glioblastoma, as well as the potential for synergies with a combinatorial, immunotherapeutic approach. The impact and progress in human cancer, including pancreatic cancer, head and neck cancer, bladder cancer are reviewed, as are lessons learned from first-in-human CAR-T cell, DNA and dendritic cell vaccines targeting glioblastoma. Going forward, a roadmap is provided for the transformative potential of mRNA vaccines to advance cancer immunotherapy, with a particular focus on the opportunities and challenges of glioblastoma. The current landscape of glioblastoma immunotherapy and gene therapy is reviewed with an eye to combinatorial approaches harnessing RNA science. Preliminary preclinical and clinical data supports the concept that mRNA vaccines could be a viable, novel approach to prolong survival in patients with glioblastoma.

Abstract Background To study the shared genetic structure between autoimmune diseases and B-cell acute lymphoblastic leukemia (B-ALL) and identify the shared risk loci and genes and genetic mechanisms involved. Methods Based on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic overlaps between autoimmune diseases and B-ALL, and cross-trait pleiotropic analysis was performed to detect shared pleiotropic loci and genes. A series of functional annotation and tissue-specific analysis were performed to determine the influence of pleiotropic genes. The heritability enrichment analysis was used to detect crucial immune cells and tissues. Finally, bidirectional Mendelian randomization (MR) methods were utilized to investigate the casual associations. Results Our research highlighted shared genetic mechanisms between seven autoimmune disorders and B-ALL. A total of 73 pleiotropic loci were identified at the genome-wide significance level (P

Abstract Background The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). Methods 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. Results Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P

Abstract To explore the effect of different stress environments on fault-slip rockbursts. Bidirectional shear friction experiments with different lateral pressures were conducted on precracked syenogranites buried at 800 m. The macroscopic statistical parameters (cumulative number of AE events, magnitude and b value) and local characteristic parameters (amplitude and dominant frequency) of acoustic emission during the stick-slip process under different lateral pressures were investigated. In addition, based on fractal theory, the nonlinear characteristics of AE spectrum were analyzed. On this basis, the microscopic mechanism of fault stick-slip was discussed. The results show that the lateral pressure influences the friction strength of the fault and stick-slip motion characteristics. With increasing lateral pressure, the proportion of transgranular shear fractures increases, which leads to an increase of cumulative number of AE events and magnitude. The periodic decrease in the b value is more significant at high lateral pressure. There is a good correlation between a high-magnitude AE event and a stress drop. The AE frequency with phased response characteristics can be used to effectively identify the evolution of fault stick-slip instability at the laboratory scale. A sharp increase in the amplitude of the dominant frequency can be regarded as one of the precursory features of fault stick-slip instability. The AE frequency spectra have multifractal characteristics, that differ among the different stages. The maximum multifractal dimension and spectral width can reflect the difference in energy released during fault stick-slip motion.

Peanut (Arachis hypogaea L.) is an oilseed crop grown worldwide. Flavonoids have profound benefits for plant growth and development because of their powerful antioxidant properties. Seed vigor is an important indicator of seed quality. However, how flavonoids impact seed vigor formation in large-seed peanuts is still poorly understood. Here, we profiled flavonoids, phytohormones, and transcriptomes of developing seeds of large-seed peanut varieties with low (ZP06) and high (H8107) seed vigor. A total of 165 flavonoids were identified, 51 of which were differentially accumulated in ZP06 and H8107. Lower levels of dihydromyricetin (0.28 times) and hesperetin-7-O-glucoside (0.26 times) were observed in ZP06 seeds than in H8107. All flavonoid biosynthesis structural genes were down-regulated in ZP06. The different hormone levels found in ZP06 and H8107 seeds could be associated with the expression of flavonoid biosynthesis genes via MYB and bHLH transcription factors. Dihydromyricetin could relate to ZP06′s poor seed vigor by impacting its seed antioxidant properties. Thus, the presence of flavonoids in large-seed peanuts could contribute to their physiological quality and germination potential through controlling the accumulation of reactive oxygen species to improve seed antioxidant properties.

Nowadays, human customer service is increasingly being replaced by artificial intelligence (AI) customer service agents. Service recovery plays a crucial role in shaping consumer experiences and business profitability. The realism of AI agents can significantly impact users’ attitudes and behaviors. However, it remains unclear how different types of realism in AI customer service agents affect customers during service recovery. Drawing on social response theory and expectation–confirmation theory, this study explores the impact of AI agents’ realism on consumer satisfaction and repeat purchase behavior during service recovery, as well as the underlying mechanisms of this effect. We collected data from 784 participants in three studies. Study 1 results show that form realism and behavioral realism of AI customer service agents affect customer satisfaction in successful service recovery situations. Study 2 indicates that the interaction effect of form realism and behavioral realism only influence satisfaction customer satisfaction and repeat purchase intention in terms of failed service recovery. Study 3 further explores the mechanism of action in failed service recovery, finding that perceived warmth and competence mediate the relationship between realism and satisfaction. We systematically examine the influence of the realism of AI customer service agents on consumer satisfaction across distinct success and failure service recovery scenarios, effectively addressing a critical research void. Additionally, our findings offer valuable insights to business managers, empowering them with actionable strategies for enhancing consumer satisfaction across varied consumption contexts and effectively mitigating the repercussions of consumption failures.

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p

Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder that affects a significant portion of aging population. Early detection of PD symptoms is crucial to prevent the progression of the disease. Research has revealed that gait attributes can provide valuable insights into PD symptoms. The gait acquisition techniques used in current research can be broadly divided into two categories: vision-based and sensor-based. The markerless vision-based classification model has become a prominent research trend due to its simplicity, low cost and patient comfort. In this study, we propose a novel markerless vision-based approach to obtain gait features from participants' gait videos. A dataset containing gait videos from normal subjects and PD patients were collected, along with a control group of 25 healthy adults. The participants were requested to perform a Timed Up and Go (TUG) test, during which their walking sequences were recorded using two smartphones positioned at different angles, namely side and front. A multi-person pose estimator is used to estimate human skeletal joint points from the collected gait videos. Different gait features associated with PD including stride length, number of steps taken during turn, turning duration, speed and cadence are derived from these key point information to perform PD detection. Experimental results show that the proposed solution achieves an accuracy of 89.39%. The study's findings demonstrate the potential of markerless vision-based gait acquisition techniques for early detection of PD symptoms.

Abstract Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient’s digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients’ prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.

Abstract Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson’s disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated α-synuclein (p-α-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-α-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to α-synuclein preformed fibril (α-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-α-syn and TLR2. Furthermore, the role of TLR2 in p-α-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-α-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of α-syn PFF induced a time-dependent loss of viability, and p-α-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-α-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-α-syn/ TLR2 signaling pathway.

With vertical stacking, 3D NAND’s flash memory can achieve continuous capacity growth. However, the endurance variation between the stacked layers becomes more and more significant due to process variation, which will lead to the underutilization of many pages and seriously affect the lifetime of 3D NAND’s flash memory. We investigated the endurance variation characteristics between layers and divided the stacked layers into the top, middle, and bottom layers according to the endurance characteristics. We found that the endurance of the bottom layer pages is much weaker than that of the other two layers, which is the primary factor that affects the lifetime of 3D NAND’s flash memory. In response to this endurance variation feature, we proposed a new layer-aware write strategy, called LA-Write. First of all, the write–skip unit in LA-Write will reduce the wear pressure of the pages through write–skip operations. Secondly, LA-Write maintains a layer-aware table, which stores the probability of pages in different layers performing the write–skip operation. Setting the probability of the bottom pages to the highest value will result in more write–skip operations on the bottom layers, mitigating endurance variations between layers. We carried out our experiments of LA-Write on DiskSim, a popular SSD simulator. Compared to existing schemes, experimental results show that LA-Write can greatly increase SSD’s lifetime.

Due to photovoltaic (PV) power generation depending on the environment, its output power is volatile, and effectively dealing with its power fluctuation has become a key concern. Aiming at this problem, this article presents an optical storage cooperative control technology based on an Alternating Sequence Filter (ASF), which controls the power management of the Energy Storage System (ESS) consisting of a vanadium redox battery, battery, and supercapacitor. Firstly, an ASF is designed to stabilize the PV power generation by alternating sequence and improve system response speed. Secondly, according to the output signal of the filter, the charge and discharge of the three energy storage units are dynamically adjusted, and the power fluctuation is compensated in real-time to improve the system stability and conversion efficiency. Finally, the simulation results of actual illumination show that the control strategy calls the ESS to stabilize the power fluctuation, so that the power of the direct current bus is stabilized at about 15 kw, and the fluctuation is maintained between −4.48% and 4.05%. The strategy significantly reduces power fluctuation and improves the dynamic response ability and energy storage utilization of the system.

Abstract Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig’s epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.

The common carp (Cyprinus carpio L., COC, 2n = 100) is one of the most widely consumed and distributed freshwater fish in the world. It ranks fourth in total freshwater aquaculture volume in various regions of China, behind Ctenopharyngodon idella, Hypophthalmichthys molitrix, and Aristichthys nobilis. However, in recent years, environmental degradation, inbreeding, disordered breeding, and other adverse effects have caused problems such as low seed quality and poor disease and stress resistance of the carp. In our laboratory, we developed two types of improved diploid carp the hybrid F1 of common carp (♀) × blunt snout bream (Megalobrama amblycephala, BSB, 2n = 48) (♂). To investigate the differences between IDC and IDMC compared to COC, in this study we compared the relevant characteristics of these two types of improved carp with those of COC in terms of muscle nutrient composition, intermuscular bone type, and number. The results showed that among the muscle nutrients, IDC had a higher protein content (18.50%) and lower carbohydrate content (0.70%). In addition, the unsaturated fatty acid content of IDC (3.45%) and IDMC (1.25%) were significantly higher than that of COC (P

Abstract Background Assessment of growth-related or treatment-related changes in the maxilla requires a reliable method of superimposition. Such methods are well established for two-dimensional (2D) cephalometric images but not yet for three-dimensions (3D). The aims of this study were to identify natural reference structures (NRS) for the maxilla in growing patients in 3D, opportunistically using orthodontic mini-screws as reference; and to test the applicability of the proposed NRS for maxillary superimposition by assessing the concordance of this approach with Björk’s ‘stable reference structures’ in lateral projection. Methods The stability of the mini-screws was tested on longitudinal pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images by measuring the distance changes between screws. After verifying the stability of the mini-screws, rigid registration was performed for aligning the stable mini-screws. Then, non-rigid registration was used to establish the dense voxel-correspondence among CBCT images and calculate the displacement of each voxel belonging to the maxilla relative to the mini-screws. The displacement vectors were transformed to a standardized maxillary template to categorize the stability of the internal structures statistically. Those voxels that displaced less relative to the mini-screws were considered as the natural reference structures (NRS) for the maxilla. Test samples included another dataset of longitudinal CBCT scans. They were used to evaluate the applicability of the proposed NRS for maxillary superimposition. We assessed whether aligning the maxilla with proposed NRS is in concordance with the maxillary internal reference structures superimposition in the traditional 2D lateral view as suggested by Björk. This was quantitively assessed by comparing the mean sagittal and vertical tooth movements for both superimposition methods. Results The stability of the mini-screws was tested on 10 pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images (T1: 12.9 ± 0.8 yrs, T2: 14.8 ± 0.7 yrs). Both the loaded and the unloaded mini-screws were shown to be stable during orthodontic treatment, which indicates that they can be used as reference points. By analyzing the deformation map of the maxilla, we confirmed that the infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm distal to incisor foramen except the palatal suture) were stable during growth. Another dataset of longitudinal CBCT scans (T1: 12.2 ± 0.63 yrs, T2: 15.2 ± 0.96 yrs) was used to assess the concordance of this approach with Björk’s ‘stable reference structures’. The movement of the maxillary first molar and central incisor showed no statistically significant difference when superimposing the test images with the proposed NRS or with the classic Björk maxillary superimposition in the lateral view. Conclusions The infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm posterior to incisal foramen except the palatal suture) were identified as stable regions in the maxilla. These stable structures can be used for maxillary superimposition in 3D and generate comparable results to Björk superimposition in the lateral view.

Abstract Meconopsis biluoensis, a new species of Papaveraceae in an alpine meadow from Yunnan, Southwest China, is described and illustrated. Morphologically, it resembles Meconopsis georgei, while it is distinct in acaulescent and hispid with clearly expanded bases on the leaves. A genus‐level molecular phylogenetic analysis supported the closest relationship between M. biluoensis and M. georgei. In a finer population‐level molecular phylogenetic analysis using ribosomal DNA (rDNA) and the chloroplast genome, individuals from M. biluoensis and M. georgei were clearly separated, and the extremely short branch length indicated that the two species had a very short differentiation time. The species has currently been assessed as “endangered” (EN) due to its small‐sized population and narrow distribution following the IUCN categories and criteria.

The contamination of bone defects is a serious therapeutic problem. The treatment of infected bone defects involves rigorous infection control followed by bone reconstruction. Considering these two processes, the development of biomaterials possessing antibacterial and osteogenic properties offers a promising approach for the treatment of infected bone defects. In this study, a dual-functional, thermosensitive, and injectable hydrogel composed of chitosan (CS), quaternized CS (QCS), and nano-hydroxyapatite (nHA) was designed, and the ratio of CS to QCS in the hydrogel was optimized to enhance the antibacterial efficacy of CS while reducing the cytotoxicity of QCS. In vitro studies demonstrated that the hydrogel with an 85 %:15 % ratio of CS to QCS exhibited excellent biocompatibility and antibacterial properties while also possessing suitable mechanical characteristics and degradability. The incorporation of nHA into the hydrogel enhanced MC3T3-E1 proliferation and osteogenic differentiation. Moreover, this hydrogel demonstrated superior in vivo therapeutic effectiveness in a rabbit model of infected bone defect. In summary, this study provides a promising material design and a comprehensive one-step treatment strategy for infected bone defects.

Summary: The efficacy of chimeric antigen receptor (CAR) T cell immunotherapy is limited by insufficient infiltration and activation of T cells due to the immunosuppressive tumor microenvironment. Preclinical studies with optimized mouse CAR T cells in immunocompetent mouse cancer models will help define the mechanisms underlying immunotherapy resistance. Here, we present a protocol for preparing mouse T cells and generating CAR T cells. We then detail procedures for testing their therapeutic efficacy and tracking them in a syngeneic mouse glioma model.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression‐like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH‐dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression‐like behaviors in both male and female mice. Mechanistically, it is found that brain‐derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant‐like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant‐like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant‐like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant‐like role of the LCTH‐dLSSST pathway in depression via BDNF‐TrkB signaling.

Abstract The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor prognosis and even increased mortality. Understanding the integrative nature of HH signaling pathway has opened up the potential for new therapeutic targets for cancer. A variety of drugs have been developed, including small molecule inhibitors, natural compounds, and long non-coding RNA (LncRNA), some of which are approved for clinical use. This review outlines recent discoveries of HH signaling in tissue homeostasis and cancer and discusses how these advances are paving the way for the development of new biologically based therapies for cancer. Furthermore, we address status quo and limitations of targeted therapies of HH signaling pathway. Insights from this review will help readers understand the function of HH signaling in homeostasis and cancer, as well as opportunities and challenges of therapeutic targets for cancer.

Abstract Background Graduate education is the main approach to training high-level innovative elites. With the expansion of the scale of graduate education in China, it has gradually emerged that the lack of innovation ability of graduate students is recognized as the primary problem in graduate education. How to comprehensively improve the quality of postgraduate teaching has become the core task of educational reform and development. However, data about the current cultivation and development of the innovative ability of graduate students in China is limited. Methods A questionnaire survey was conducted among medical postgraduate students. Descriptive statistics and multiple regression analysis methods were used to analyze the data to describe the current innovation ability in advanced medical education and potential influence factors. Results A total of 1241 medical students were surveyed, according to the results of questionnaire data analysis. The proportion of subjects who participated in the College Student’s Entrepreneurship and Innovation program or any other scientific research programs are fairly high which are 46.82% and 29.20% respectively. Most of the participants are observed with high levels of self-motivation and active learning and have good performance in creative thinking. However, only a small number of participants (16.6%) reported academic achievements such as publications. Most of the students are satisfied with the current scientific research environment and think that the current postgraduate training system is qualified for the cultivation of innovation ability, and expects the inclusion of course specialized in systemic medicine and medical informatics in the curricula. Multiple logistic regression results showed that among the factors studied, gender, medical specialties, and types of master’s degrees are associated with cognition & skills, academic performance, and creativity. Conclusions It will be important to incorporate more techniques for creating and improving creativity in the curricula of the current postgraduate education, especially for courses such as systemic medicine and informatics. Guidance in earlier school life can stimulate creativity and an early introduction to scientific research work will facilitate innovative thinking and behavior. Scientific research programs such as the National Innovation and Entrepreneurship Training for the universities of PRC have been widely implemented in the undergraduate education system throughout the country. However, the training effectiveness of the current scientific research programs is worth improving.

Structural damage is significantly influenced by the various parameters of a close-in explosion. To establish a close-in blast loading model for cylindrical charges according to these parameters, a series of field experiments and a systematic numerical analysis were conducted. A high-fidelity finite element model developed using AUTODYN was first validated using blast data collected from field tests conducted in this and previous studies. A quantitative analysis was then performed to determine the influence of the charge shape, aspect ratio (length to diameter), orientation, and detonation configuration on the characteristics and distributions of the blast loading (incident peak overpressure and impulse) according to scaled distance. The results revealed that the secondary peak overpressure generated by a cylindrical charge was mainly distributed along the axial direction and was smaller than the overpressure generated by an equivalent spherical charge. The effects of charge shape on the blast loading at 45° and 67.5° in the axial plane could be neglected at scaled distances greater than 2 m/kg1/3; the effect of aspect ratios greater than 2 on the peak overpressure in the 90° (radial) direction could be neglected at all scaled distances; and double-end detonation increased the radial blast loading by up to 60% compared to single-end detonation. Finally, an empirical cylindrical charge blast loading model was developed considering the influences of charge aspect ratio, orientation, and detonation configuration. The results obtained in this study can serve as a reference for the design of blast tests using cylindrical charges and aid engineers in the design of blast-resistant structures.

The treatment of bone defects is a difficult problem in orthopedics. The excessive destruction of local bone tissue at defect sites destroys blood supply and renders bone regeneration insufficient, which further leads to delayed union or even nonunion. To solve this problem, in this study, we incorporated icariin into alginate/mineralized collagen (AMC) hydrogel and then placed the drug-loaded hydrogel into the pores of a 3D-printed porous titanium alloy (AMCI/PTi) scaffold to prepare a bioactive scaffold with the dual functions of promoting angiogenesis and bone regeneration. The experimental results showed that the ACMI/PTi scaffold had suitable mechanical properties, sustained drug release function, and excellent biocompatibility. The released icariin and mineralized collagen (MC) synergistically promoted angiogenesis and osteogenic differentiation in vitro. After implantation into a rabbit radius defect, the composite scaffold showed a satisfactory effect in promoting bone repair. Therefore, this composite dual-functional scaffold could meet the requirements of bone defect treatment and provide a promising strategy for the repair of large segmental bone defects in clinic.

ObjectiveThis study aims to explore the predictive value of the Controlling Nutritional Status (CONUT) score for prostate cancer (PCa) diagnosis.MethodsThe data of 114 patients who underwent prostate needle biopsies from June 2020 to December 2022 were retrospectively analyzed. The relationship between CONUT score and various clinical factors as well as PCa diagnosis was evaluated.ResultsThe pathological results classified patients into the PCa (n = 38) and non-PCa (n = 76) groups. Compared with the non-PCa group, the PCa group exhibited statistically significant differences in age, prostate-specific antigen (PSA), PSA density (PSAD), the proportion of PI-RADS ≥ 3 in mpMRI, and the CONUT score, prostate volume, lymphocyte count, and total cholesterol concentration (p < 0.05). ROC curve analyses indicated the diagnostic accuracy as follows: age (AUC = 0.709), prostate volume (AUC = 0.652), PSA (AUC = 0.689), PSAD (AUC = 0.76), PI-RADS ≥ 3 in mpMRI (AUC = 0.846), and CONUT score (AUC = 0.687). When CONUT score was combined with PSA and PSAD, AUC increased to 0.784. The AUC of CONUT score combined with PSA, PSAD, and mpMRI was 0.881, indicates a higher diagnostic value. Based on the optimal cut-off value of CONUT score, compared with the low CONUT score group, the high CONUT score group has a higher positive rate of PCa diagnosis (p < 0.05).ConclusionCONUT score is an excellent auxiliary index for PCa diagnosis in addition to the commonly used PSA, PSAD, and mpMRI in clinical practice. Further prospective trials with a larger sample size are warranted to confirm the present study findings.

Liver steatosis is a common metabolic disorder resulting from imbalanced lipid metabolism, which involves various processes such as de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and VLDL secretion. In this study, we discovered that KLF2, a transcription factor, plays a crucial role in regulating lipid metabolism in the liver. Overexpression of KLF2 in the liver of db/db mice, C57BL/6J mice, and Cd36-/- mice fed on a normal diet resulted in increased lipid content in the liver. Additionally, transgenic mice (ALB-Klf2) that overexpressed Klf2 in the liver developed liver steatosis after being fed a normal diet. We found that KLF2 promotes lipogenesis by increasing the expression of SCAP, a chaperone that facilitates the activation of SREBP, the master transcription factor for lipogenic gene expression. Our mechanism studies revealed that KLF2 enhances lipogenesis in the liver by binding to the promoter of SCAP and increasing the expression of genes involved in fatty acid synthesis. Reduction of KLF2 expression led to a decrease in SCAP expression and a reduction in the expression of SREBP1 target genes involved in lipogenesis. Overexpression of KLF2 also increased the activation of SREBP2 and the mRNA levels of its downstream target SOAT1. In C57BL/6J mice fed a high-fat diet, overexpression of Klf2 increased blood VLDL secretion, while reducing its expression decreased blood cholesterol levels. Our study emphasizes the novelty that hepatic KLF2 plays a critical role in regulating lipid metabolism through the KLF2/SCAP/SREBPs pathway, which is essential for hepatic lipogenesis and maintaining blood cholesterol homeostasis.

ObjectiveSarcopenia and cognitive impairment often coexist in the elderly. In this study, we investigated the causal relationship between sarcopenia-related muscle characteristics and cognitive performance.MethodsWe used linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR) analyses to estimate genetic correlations and causal relationships between genetically predicted sarcopenia-related muscle traits and cognitive function, as well as cognitive function-based discovery samples and replicated samples. Estimated effect sizes were derived from a fixed-effects meta-analysis.ResultsOur univariate genome-wide association study (GWAS) meta-analysis indicated a causal relationship between appendicular lean mass (ALM) (β = 0.049; 95% confidence interval (CI): 0.032-0.066, P < 0.001) and walking pace (β = 0.349; 95% CI: 0.210-0.487, P < 0.001) with cognitive function, where a causal relationship existed between ALM in both male and female (βALM-Male(M) = 0.060; 95% CI: 0.031-0.089, PALM-M < 0.001; βALM-Female(F) = 0.045; 95% CI: 0.020-0.069, PALM-F < 0.001) with cognitive function. Low grip strength was not causally associated with cognitive function (β = -0.045; 95% CI: -0.092 - -0.002, P = 0.062). A reverse causality GWAS meta-analysis showed a causal relationship between cognitive function and ALM (β = 0.033; 95% CI: 0.018-0.048, P < 0.001) and walking pace (β = 0.039; 95% CI: 0.033-0.051, P < 0.001), where ALM in both male and female showed a causality (βALM-M = 0.041; 95% CI: 0.019-0.063, PALM-M < 0.001; βALM-F = 0.034; 95% CI: 0.010-0.058, PALM-F = 0.005). Cognitive function was not causally related to low grip strength (β = -0.024; 95% CI: -0.073-0.025, P = 0.344). Multivariable MR1 (MVMR1) analyses showed a significant causal relationship for ALM (β = 0.077; 95% CI: 0.044-0.109, P = 0.000) and walking pace (β = 0.579; 95% CI: 0.383-0.775, P = 0.000) and cognitive function. Multivariable MR2 (MVMR2) multivariate analysis showed that ALM causality remained (β = 0.069; 95% CI: 0.033-0.106, P = 0.000), and walking pace (β = 0.589; 95% CI: 0.372-0.806, P = 0.000).ConclusionsBidirectional two-sample MR demonstrated that sarcopenia-related muscle characteristics and cognitive performance were positive causal genetic risk factors for each other, while a multivariable MR study demonstrated that low ALM and a slow walking pace were causally involved in reduced cognitive performance. This study suggests a causal relationship between sarcopenia and cognitive impairment in older adults and provide new ideas for prevention and treatment.