Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption.

Mechanical loading is required for bone homeostasis, but the underlying mechanism is still unclear. Our previous studies revealed that the mechanical protein polycystin-1 (PC1, encoded by Pkd1) is critical for bone formation. However, the role of PC1 in bone resorption is unknown. Here, we found that PC1 directly regulates osteoclastogenesis and bone resorption. The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts, decreased bone resorption, and increased bone mass. A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease, which is mainly caused by loss-of-function mutation of the PKD1 gene, is associated with a lower risk of hip fracture than those with other chronic kidney diseases. Moreover, mice with osteoclast-specific knockout of Pkd1 showed complete resistance to unloading-induced bone loss. A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass. Pharmacological regulation of the PC1-TAZ axis alleviated unloading- and estrogen deficiency- induced bone loss. Thus, the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Agreement between quality of life assessed using family proxy and child self-reports among children with hematologic malignancy.

Evidence-based literature recognizes that the different degrees of agreement between a child self-report and a proxy-report depend on the characteristics of the domains, the child's age and illness, the proxy's own perspective on QoL, and family attendance during the child's hospitalization. This study aims to determine the degree of agreement between proxy-reports and child self-reports on quality of life (QoL) for children with hematologic malignancy ranging in age from 5 to 18 years who are undergoing treatment. We retrieved clinical QoL data from a study titled "Dynamic change in QoL for Vietnamese children with hematologic malignancy" from April 2021 to December 2022. To evaluate the magnitude of agreement between self-reports and proxy-reports, intraclass correlation coefficients (ICCs) for 259 pairs of measurements were quantified. Using independent t tests, the mean differences between self-reports and proxy-reports were tested. Moderate agreement was consistent through all age groups for five subscales, including physical, psychosocial, pain, nausea, and procedural anxiety (ICCs ranged from 0.53 to 0.74). The weakest agreement appeared in two groups, subjects aged 5-7 years and 13-18 years on six domains (school, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication) (-0.01 to 0.49). Child self-rating was consistently higher than that of proxies for the physical, emotional, and nausea domains among children aged 5-7 years and for procedural anxiety, treatment anxiety, and cognitive problems among children aged 8-12 years.    Conclusion: The agreement level of self-reports and proxy-reports was differently distributed by child age and the PedsQL domains. The proxy children agreement on QoL among children with hematologic malignancy was divergent according to the different age groups, which could potentially be explained by proxy-child bonding at different stages of childhood development. Our recommendation for future studies is to explore children's age as a potential factor influencing proxy agreement on QoL among children with cancer. What is Known: • Children and their proxies may think differently about quality of life (QoL). • Comparing two sources of data (i.e., child and proxy) on aspects of QoL can help identify the discrepancies between children's perceptions of their QoL and their parents' perceptions. This can be useful in terms of identifying potential areas for improvement or concern and may also be helpful in making decisions about treatment and care. What is New: • Our study results demonstrated that proxies who comprised children aged 5-7 years or 13-18 years reported differently among domains that cannot be expressed verbally or with body language, including cognitive problems, perceived physical appearance, and communication. • Children generally perceived their QoL to be better than their proxies. Therefore, a more comprehensive understanding of children's QoL may require the consideration of multiple sources of data from various perspectives.

Vegetation redistribution is predicted to intensify soil organic carbon loss under future climate changes on the Tibetan Plateau.

Vegetation redistribution may bring unexpected climate-soil carbon cycling in terrestrial biomes. However, whether and how vegetation redistribution alters the soil carbon pool under climate change is still poorly understood on the Tibetan Plateau. Here, we applied the G-Range model to simulate the cover of herbs, shrubs and trees, net primary productivity (NPP) and soil organic carbon density (SOCD) at the depth of 60 cm on Tibetan Plateau for the individual years 2020 and 2060, using climate projection for Representative Concentration Pathways (RCP) 4.5 and RCP8.5 scenarios with the RegCM4.6 model system. Vegetation redistribution was defined as the transitions in bare ground, herbs, shrubs and trees between 2020 and 2060, with approximately 57.9 % (RCP4.5) and 59 % (RCP8.5) of the area will redistribute vegetation over the whole Tibetan Plateau. The vegetation cover will increase by about 2.4 % (RCP4.5) and 1.9 % (RCP8.5), while the NPP and SOCD will decrease by about -14.3 g C m-2 yr-1 and -907 g C m-2 (RCP4.5), and -1.8 g C m-2 yr-1and -920 g C m-2 (RCP8.5). Shrubs and trees will expand in the east, and herbs will expand in the northwest part of the Plateau. These areas are projected to be hotspots with greater SOCD reduction in response to future climate change, and will include lower net plant carbon input due to the negative NPP. Our study indicates that the SOC pool will become a carbon source under increased air temperature and rainfall on the Tibetan Plateau by 2060, especially for the area with vegetation redistribution. These results revealed the potential risk of vegetation redistribution under climate change in alpine ecosystems, indicating the policymakers need to pay attention on the vegetation redistribution to mitigate the soil carbon emission and achieve the goal of carbon neutrality on the Tibetan Plateau.

Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults With Osteoporosis/Fractures.

OBJECTIVE: To evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. METHODS: This multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. RESULTS: A total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D â‰§20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. CONCLUSION: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents.

Background: The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation. Aims: The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety. Methods: 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale, and 716 adolescents who scored ≥5 on both scales were selected as participants. Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms. Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9. A comparison was made between the depression-anxiety symptom networks of the two groups. Results: 'Restlessness', 'sad mood' and 'trouble relaxing' were the most prominent central symptoms in the depression-anxiety symptom network, and 'restlessness', 'nervousness' and 'reduced movement' were the bridge symptoms in this network. 'Sad mood' was found to be directly related to 'suicide ideation' with the highest variance. The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group, with 'restlessness' and 'sad mood' exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group. Conclusion: Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

Insights into Reactive Oxygen Species Production-Scavenging System Involved in Sugarcane Response to Xanthomonas albilineans Infection under Drought Stress.

Plants must adapt to the complex effects of several stressors brought on by global warming, which may result in interaction and superposition effects between diverse stressors. Few reports are available on how drought stress affects Xanthomonas albilineans (Xa) infection in sugarcane (Saccharum spp. hybrids). Drought and leaf scald resistance were identified on 16 sugarcane cultivars using Xa inoculation and soil drought treatments, respectively. Subsequently, four cultivars contrasting to drought and leaf scald resistance were used to explore the mechanisms of drought affecting Xa-sugarcane interaction. Drought stress significantly increased the occurrence of leaf scald and Xa populations in susceptible cultivars but had no obvious effect on resistant cultivars. The ROS bursting and scavenging system was significantly activated in sugarcane in the process of Xa infection, particularly in the resistant cultivars. Compared with Xa infection alone, defense response via the ROS generating and scavenging system was obviously weakened in sugarcane (especially in susceptible cultivars) under Xa infection plus drought stress. Collectively, ROS might play a crucial role involving sugarcane defense against combined effects of Xa infection and drought stress.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Gut microbiota moderates multimodal brain structure-function integration and behavioral cognition in growth hormone deficient children.

Background Previous brain studies of growth hormone deficiency (GHD) often used single-mode neuroimaging, missing the complexity captured by multimodal data. Growth hormone affects gut microbiota and metabolism in GHD. However, from a gut-brain axis perspective, the relationship between abnormal GHD brain development and microbiota alterations remains unclear. The ultimate goal is to uncover the manifestations underlying gut-brain axis (GBA) abnormalities in GHD and idiopathic short stature (ISS). Methods Participants included 23 GHD and 25 ISS children. The fusion independent component analysis was applied to integrat multimodal brain datas (high resolution structural, diffusion tensor, and resting state functional MRI) covering regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and White matter fractional anisotropy (FA). Gut microbiome diversity and metabolites were analyzed using 16S sequencing and proton nuclear magnetic resonance (1H-NMR). Associations between multimodal neuroimaging and cognition were assessed using moderation analysis. Results Six components (ReHo, ALFF, and FA) differed significantly between GHD and ISS patients, with three functional components linked to processing speed. GHD individuals showed higher levels of acetate in microbiota metabolism. Higher alpha diversity in GHD strengthened connections between ReHo-IC1, ReHo-IC5, ALFF-IC1, and processing speed, while increasing Agathobacter levels in ISS weakened the link between ALFF-IC1 and speech comprehension. Conclusions Our findings uncover differing brain structure and functional fusion in GHD, alongside microbiota metabolism of short-chain fatty acids. Additionally, microbiome influences connections between neuroimaging and cognition, offering insight into diverse gut-brain axis patterns in GHD and ISS, enhancing our understanding of the disease's pathophysiology and interventions.

Oxygen-Vacancy-Mediated Large Binding Energy Exciton Dissociation in Nb3O7(OH) Nanorods with High Electron Mobility for CO2 Photoreduction.

Despite the excellent performance of Nb3O7(OH) in dye-sensitized solar cells and catalysis, its charge separation, transport, and structural properties remain poorly understood. Herein, the Nb3O7(OH) nanorods were prepared, and their structural characteristics, optoelectronic properties, and carrier mobility were also analyzed and investigated through a series of complex characterizations. Theoretical prediction suggested that the exciton binding energy of Nb3O7(OH) could be as high as 100.49 meV. The temperature-dependent photoluminescence (PL) of Nb3O7(OH) nanorods revealed two activation energies, and a higher proportion of long-lived components observed in the photoluminescence decay indicated effective electron trapping. That is, two energy states were present, hindering photogenerated charge recombination and promoting photocatalytic action. Current-voltage characteristics of the Nb3O7(OH) nanorod film were analyzed, revealing an ultrahigh carrier mobility of ∼310 cm2/V·s, ensuring fast and efficient electron transfer. Furthermore, Nb3O7(OH) nanorods were employed to reduce CO2, resulting in the effective production of CO and CH4. Overall, considering the presence of hydroxyl pairs on the surface of Nb3O7(OH), which facilitate the formation of the frustrated Lewis acid-base pairs and the activation of CO2, together with its effective electron trapping and charge transport, give Nb3O7(OH) nanorods a promising potential for CO2 reduction.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

A Deep Learning Application of Capsule Endoscopic Gastric Structure Recognition Based on a Transformer Model.

BACKGROUND: Gastric structure recognition systems have become increasingly necessary for the accurate diagnosis of gastric lesions in capsule endoscopy. Deep learning, especially using transformer models, has shown great potential in the recognition of gastrointestinal (GI) images according to self-attention. This study aims to establish an identification model of capsule endoscopy gastric structures to improve the clinical applicability of deep learning to endoscopic image recognition. METHODS: A total of 3343 wireless capsule endoscopy videos collected at Nanfang Hospital between 2011 and 2021 were used for unsupervised pretraining, while 2433 were for training and 118 were for validation. Fifteen upper GI structures were selected for quantifying the examination quality. We also conducted a comparison of the classification performance between the artificial intelligence model and endoscopists by the accuracy, sensitivity, specificity, and positive and negative predictive values. RESULTS: The transformer-based AI model reached a relatively high level of diagnostic accuracy in gastric structure recognition. Regarding the performance of identifying 15 upper GI structures, the AI model achieved a macroaverage accuracy of 99.6% (95% CI: 99.5-99.7), a macroaverage sensitivity of 96.4% (95% CI: 95.3-97.5), and a macroaverage specificity of 99.8% (95% CI: 99.7-99.9) and achieved a high level of interobserver agreement with endoscopists. CONCLUSIONS: The transformer-based AI model can accurately evaluate the gastric structure information of capsule endoscopy with the same performance as that of endoscopists, which will provide tremendous help for doctors in making a diagnosis from a large number of images and improve the efficiency of examination.

An ensemble-acute lymphoblastic leukemia model for acute lymphoblastic leukemia image classification.

The timely diagnosis of acute lymphoblastic leukemia (ALL) is of paramount importance for enhancing the treatment efficacy and the survival rates of patients. In this study, we seek to introduce an ensemble-ALL model for the image classification of ALL, with the goal of enhancing early diagnostic capabilities and streamlining the diagnostic and treatment processes for medical practitioners. In this study, a publicly available dataset is partitioned into training, validation, and test sets. A diverse set of convolutional neural networks, including InceptionV3, EfficientNetB4, ResNet50, CONV_POOL-CNN, ALL-CNN, Network in Network, and AlexNet, are employed for training. The top-performing four individual models are meticulously chosen and integrated with the squeeze-and-excitation (SE) module. Furthermore, the two most effective SE-embedded models are harmoniously combined to create the proposed ensemble-ALL model. This model leverages the Bayesian optimization algorithm to enhance its performance. The proposed ensemble-ALL model attains remarkable accuracy, precision, recall, F1-score, and kappa scores, registering at 96.26, 96.26, 96.26, 96.25, and 91.36%, respectively. These results surpass the benchmarks set by state-of-the-art studies in the realm of ALL image classification. This model represents a valuable contribution to the field of medical image recognition, particularly in the diagnosis of acute lymphoblastic leukemia, and it offers the potential to enhance the efficiency and accuracy of medical professionals in the diagnostic and treatment processes.

Factors Related to Mpox-Vaccine Uptake among Men Who Have Sex with Men in Taiwan: Roles of Information Sources and Emotional Problems.

An mpox outbreak occurred suddenly and rapidly spread worldwide in 2022. Research has demonstrated a link between the sexual behavior of men who have sex with men (MSM) and the contraction of mpox. This study assessed the factors related to mpox-vaccine uptake among MSM in Taiwan, focusing on the roles of information sources and emotional problems. In total, 389 MSM participated in an online survey. Data on the participants' vaccination statuses; anxiety symptoms, which were assessed using the State-Trait Anxiety Inventory; depressive symptoms, which were assessed using the Center for Epidemiologic Studies Depression Scale; and risk perceptions of contracting mpox were collected. Factors related to mpox-vaccine uptake were examined using a multivariable logistic regression model. The results revealed that MSM who were older (p < 0.001), perceived a higher risk of contracting mpox (p = 0.040), and received mpox information from health-care providers (p < 0.001) were more likely to receive mpox vaccination, whereas MSM who reported a greater severity of depression (p = 0.017) were less likely to receive mpox vaccination. However, age did not moderate the associations of perceiving a higher risk of contracting mpox, receiving mpox information from health-care providers, and depression with having an mpox vaccination. Health-care providers should consider these factors when developing intervention programs for enhancing mpox-vaccine uptake among MSM.

Identification, expression analysis, and functional verification of three opsin genes related to the phototactic behaviour of Ostrinia furnacalis.

Ostrinia furnacalis is a disreputable herbivorous pest that poses a serious threat to corn crops. Phototaxis in nocturnal moths plays a crucial role in pest prediction and control. Insect opsins are the main component of insect visual system. However, the inherent molecular relationship between phototactic behaviour and vision of insects remains a mystery. Herein, three opsin genes were identified and cloned from O. furnacalis (OfLW, OfBL, and OfUV). Bioinformatics analysis revealed that all opsin genes had visual pigment (opsin) retinal binding sites and seven transmembrane domains. Opsin genes were distributed across different developmental stages and tissues, with the highest expression in adults and compound eyes. The photoperiod-induced assay elucidated that the expression of three opsin genes in females were higher during daytime, while their expression in males tended to increase at night. Under the sustained darkness, the expression of opsin genes increased circularly, although the increasing amplitude in males was lower when compared with females. Furthermore, the expression of OfLW, OfBL, and OfUV was upregulated under green, blue, and ultraviolet light, respectively. The results of RNA interference showed that the knockout of opsin genes decreased the phototaxis efficiency of female and male moths to green, blue, and ultraviolet light. Our results reveal that opsin genes are involved in the phototactic behaviour of moths, providing a potential target gene for pest control and a basis for further investigation on the phototactic behaviour of Lepidoptera insects.

Effects of cell morphology, physiology, biochemistry and CHS genes on four flower colors of Impatiens uliginosa.

Introduction: Flower color is one of the important ornamental traits in the plants, which plays an active role in attracting pollinators to pollinate plants and reproduce their offspring. The flower color of Impatiens uliginosa is rich, there are four main flower colors in nature: deep red, red, pink, and white. However, it remains unclear whether on four different flower colors mechanism of I. uliginosa. Methods: We investigate colorimetric measurement, observation of epidermal cells, cellular pH determination, extraction and determination of total anthocyanins and flavonoid, semi-quantitative determination of pigment components, and gene cloning and qRT-PCR of CHS genes to study four flower colors of I. uliginosa. Results: The L* and b* values were the highest in white flower, while the a* values were the highest in pink flower. The same shape of epidermal cells was observed in different flower colors, which was all irregular flat polygons, and there were partial lignification. Their cellular pH values were weakly acidic, while the pH values of the deep red flower was the highest and the white flower was the lowest. The highest pigment content of the four flower colors was total anthocyanin content. And malvidin-3-galactosidechloride (C23H25ClO12), cyanidin-3-O-glucoside (C21H21O11) and delphinidin (C15H11O7) were the main pigment components affecting the color of four different flower colors. The anthocyanin synthesis gene IuCHS was expressed in four flowers, and all three copies of it had the highest expression level in pink flower and the lowest expression level in white flower. Discussion: These results revealed the influence of main internal factors on four different flower colors of I. uliginosa, and provided a basis for further understanding of the intracellular and molecular regulatory mechanisms of flower color variation, and laid a foundation for the improvement of flower color breeding of Impatiens.

Synergistic effects of combined probiotics Bacillus pumilis D5 and Leuconostoc mesenteroide B4 on immune enhancement and disease resistance in Litopenaeus vannamei.

This study investigated the effects of two distinct probiotics, Leuconostoc mesenteroides B4 (B4) and Bacillus pumilus D5 (D5), along with their combination, on the diet of white shrimp (Litopenaeus vannamei) during an eight-week feeding trial. The diets tested included B4 + dextran at 107 CFU/g feed (the B4 group), D5 alone at 107 CFU/g feed (the D5 group), and a combination of B4 + dextran and D5 at 5 × 106 CFU/g feed each (the B4+dextran + D5 group). Relative to the control group, those administered probiotics exhibited moderate enhancements in growth. By the eighth week, the weight gain for the B4, D5, and B4+D5 groups was 696.50 ± 78.15%, 718.53 ± 130.73%, and 693.05 ± 93.79%, respectively, outperforming the control group's 691.66 ± 31.10% gain. The feed conversion ratio was most efficient in the B4 group (2.16 ± 0.06), closely followed by B4+D5 (2.21 ± 0.03) and D5 (2.22 ± 0.06), with the control group having the highest ratio (2.27 ± 0.03). While phenoloxidase activity was somewhat elevated in the B4 and D5 groups, no significant differences were noted in respiratory burst activity or total hemocyte count across all groups. Challenge tests at weeks 4 and 8 showed that the B4 + D5 combination offered superior protection against AHPND-causing Vibrio parahaemolyticus. The 4-week cumulative survival rate was highest in shrimp treated with B4 + dextran + D5 (56.25%), followed by B4 + dextran (31.25%), control (18.75%), and lowest in D5 (12.5%). By week 8, the B4 + dextran + D5 (43.75%) and B4 + dextran (37.5%) groups significantly outperformed the control group (6.25%, p < 0.05), with no significant difference observed between the D5 group (37.5%) and the control group at day 56. Analysis of the shrimp's foregut microbiota revealed an increase in unique OTUs in the B4 and B4 + D5 groups. Compared to the control, Proteobacteria abundance was reduced in all probiotic groups. Potential pathogens like Vibrio, Bacteroides, Neisseria, Botrytis, Clostridioides, and Deltaentomopoxvirus were detected in the control but were reduced or absent in probiotic groups. Beneficial microbes such as Methanobrevibacter and Dictyostelium in the B4+D5 group, and Sugiyamaella in the B4 group, showed significant increases. Probiotics also led to higher transcript levels of nitric oxide synthase in the hemocytes, and lysozyme and transglutaminase in the midgut, along with lysozyme and α2-macroglobulin in the foregut. Notably, the combined B4 + D5 probiotics synergistically enhanced the expression of superoxide dismutase and prophenoloxidase in the foregut, indicating an improved immune response. In summary, this study demonstrates that the probiotics evaluated, especially when used in combination, significantly boost the expression of specific immune-related genes, enhance the bacterial diversity and richness of the intestine, and thus prevent the colonization and proliferation of Vibrio spp. in L. vannamei.

Immune checkpoint inhibitor monotherapy is sufficient to promote microenvironmental normalization via the type I interferon pathway in PD-L1-expressing head and neck cancer.

Immune checkpoint blockers (ICBs) targeting programmed cell death protein 1 (PD-1) have been proven to be an effective first-line therapy against programmed cell death 1 ligand 1 (PD-L1; also known as CD274 molecule)-expressing head and neck squamous cell carcinoma (HNSCC) in recent KEYNOTE-048 trial. However, associated changes in the tumor microenvironment (TME) and underlying mechanisms remain elusive. Oral tumors in C57/BL6 mice were induced by administering 7,12-dimethylbenzanthracene into the buccal mucosa. Single-cell suspension was isolated from tumor tissue; proliferating cells were injected subcutaneously into the left flank of mice to establish Ajou oral cancer (AOC) cell lines. Subsequently, a syngeneic PD-L1-expressing HNSCC model was developed by injecting AOC cells into the buccal or tongue area. The model recapitulated human HNSCC molecular features and showed reliable in vivo tumorigenicity with significant PD-L1 expression. ICB monotherapy induced global changes in the TME, including vascular normalization. Furthermore, the antitumor effect of ICB monotherapy was superior to those of other therapeutic agents, including cisplatin and inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2). The ICB-induced antitumorigenicity and TME normalization were alleviated by blocking the type I interferon pathway. In summary, ICB monotherapy is sufficient to induce TME normalization in the syngeneic model; the type I interferon pathway is indispensable in realizing the effects of ICBs. Furthermore, these results explain the underlying mechanism of the efficacy of ICB monotherapy against PD-L1-expressing HNSCC in the KEYNOTE-048 trial.