A new model construction based on the knowledge graph for mining elite polyphenotype genes in crops.

Identifying polyphenotype genes that simultaneously regulate important agronomic traits (e.g., plant height, yield, and disease resistance) is critical for developing novel high-quality crop varieties. Predicting the associations between genes and traits requires the organization and analysis of multi-dimensional scientific data. The existing methods for establishing the relationships between genomic data and phenotypic data can only elucidate the associations between genes and individual traits. However, there are relatively few methods for detecting elite polyphenotype genes. In this study, a knowledge graph for traits regulating-genes was constructed by collecting data from the PubMed database and eight other databases related to the staple food crops rice, maize, and wheat as well as the model plant Arabidopsis thaliana. On the basis of the knowledge graph, a model for predicting traits regulating-genes was constructed by combining the data attributes of the gene nodes and the topological relationship attributes of the gene nodes. Additionally, a scoring method for predicting the genes regulating specific traits was developed to screen for elite polyphenotype genes. A total of 125,591 nodes and 547,224 semantic relationships were included in the knowledge graph. The accuracy of the knowledge graph-based model for predicting traits regulating-genes was 0.89, the precision rate was 0.91, the recall rate was 0.96, and the F1 value was 0.94. Moreover, 4,447 polyphenotype genes for 31 trait combinations were identified, among which the rice polyphenotype gene IPA1 and the A. thaliana polyphenotype gene CUC2 were verified via a literature search. Furthermore, the wheat gene TraesCS5A02G275900 was revealed as a potential polyphenotype gene that will need to be further characterized. Meanwhile, the result of venn diagram analysis between the polyphenotype gene datasets (consists of genes that are predicted by our model) and the transcriptome gene datasets (consists of genes that were differential expression in response to disease, drought or salt) showed approximately 70% and 54% polyphenotype genes were identified in the transcriptome datasets of Arabidopsis and rice, respectively. The application of the model driven by knowledge graph for predicting traits regulating-genes represents a novel method for detecting elite polyphenotype genes.

Characterization of the complete chloroplast genome sequence of Camellia tetracocca (Theaceae).

Camellia tetracocca H.T. Chang 1981 is an important wild relative of cultivated tea plants. Its leaves are widely used by local people to make tea, showing great economic and breeding values. We here report the complete chloroplast genome of C. tetracocca using Illumina sequencing technology. The complete chloroplast genome of C. tetracocca is 157,026 bp in length, and structurally contains a pair of inverted repeat regions (IRa and IRb, 26,052 bp) separated by a large single-copy region (LSC, 86,669 bp) and a small single-copy region (SSC, 18,253 bp). It is composed of 131 predicted genes, including 86 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. The overall GC content is 37.31%. Phylogenetic analysis among four Camellia species and 11 other close species reveals a close relationship between C. tetracocca and C. gymnogyna.

Proteomic characteristics of the aqueous humor in Uyghur patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma.

Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.

Nitrogen and sulfur cycling and their coupling mechanisms in eutrophic lake sediment microbiomes.

Microorganisms play important roles in the biogeochemical cycles of lake sediment. However, the integrated metabolic mechanisms governing nitrogen (N) and sulfur (S) cycling in eutrophic lakes remain poorly understood. Here, metagenomic analysis of field and bioreactor enriched sediment samples from a typical eutrophic lake were applied to elucidate the metabolic coupling of N and S cycling. Our results showed significant diverse genes involved in the pathways of dissimilatory sulfur metabolism, denitrification and dissimilatory nitrate reduction to ammonium (DNRA). The N and S associated functional genes and microbial groups generally showed significant correlation with the concentrations of NH4+, NO2- and SO42, while with relatively low effects from other environmental factors. The gene-based co-occurrence network indicated clear cooperative interactions between N and S cycling in the sediment. Additionally, our analysis identified key metabolic processes, including the coupled dissimilatory sulfur oxidation (DSO) and DNRA as well as the association of thiosulfate oxidation complex (SOX systems) with denitrification pathway. However, the enriched N removal microorganisms in the bioreactor ecosystem demonstrated an additional electron donor, incorporating both the SOX systems and DSO processes. Metagenome-assembled genomes-based ecological model indicated that carbohydrate metabolism is the key linking factor for the coupling of N and S cycling. Our findings uncover the coupling mechanisms of microbial N and S metabolism, involving both inorganic and organic respiration pathways in lake sediment. This study will enhance our understanding of coupled biogeochemical cycles in lake ecosystems.

Brain stimulation over the left DLPFC enhances motivation for effortful rewards in patients with major depressive disorder.

BACKGROUND: Amotivation is a typical feature in major depressive disorder (MDD), which produces reduced willingness to exert effort. The dorsolateral prefrontal cortex (DLPFC) is a crucial structure in goal-directed actions and therefore is a potential target in modulating effortful motivation. However, it remains unclear whether the intervention is effective for patients with MDD. METHODS: We employed transcranial magnetic stimulation (TMS), computational modelling and event-related potentials (ERPs) to reveal the causal relationship between the left DLPFC and motivation for effortful rewards in MDD. Fifty patients underwent both active and sham TMS sessions, each followed by performing an Effort-Expenditure for Rewards Task, during which participants chose and implemented between low-effort/low-reward and high-effort/high-reward options. RESULTS: The patients showed increased willingness to exert effort for rewards during the DLPFC facilitated session, compared with the sham session. They also had a trend in larger P3 amplitude for motivated attention toward chosen options, larger CNV during preparing for effort exertion, and larger SPN during anticipating a high reward. Besides, while behavior indexes for effortful choices were negatively related to depression severity in the sham session, this correlation was weakened in the active stimulation session. CONCLUSIONS: These findings provide behavioral, computational, and neural evidence for the left DLPFC on effortful motivation for rewards. Facilitated DLPFC improves motor preparation and value anticipation after making decisions especially for highly effortful rewards in MDD. Facilitated DLPFC also has a potential function in enhancing motivated attention during cost-benefit trade-off. This neuromodulation effect provides a potential treatment for improving motivation in clinics.

Enhancing ventrolateral prefrontal cortex activation mitigates social pain and modifies subsequent social attitudes: Insights from TMS and fMRI.

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

Probiotics for the prevention of gestational diabetes mellitus: A meta-analysis of randomized controlled trials.

Changes of intestinal microbiota have been shown to be involved in the development of gestational diabetes mellitus (GDM). We performed a meta-analysis to systematically evaluate the potential role of probiotics for the prevention of GDM. Systematic literature search was performed in electronic databases including PubMed, Cochrane library, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) to obtain relevant randomized controlled studies. A random-effects model was used to pool the results by incorporating the impact of the potential heterogeneity. Meta-regression and subgroup analyses were conducted to evaluate the source of heterogeneity. Fourteen studies involving 3527 pregnant women were included. Results showed that probiotics significantly reduced the incidence of GDM as compared to control (risk ratio [RR]: 0.71, 95% confidence interval [CI]: 0.52-0.96, P = 0.03) with significant heterogeneity (I2 = 73%). The meta-regression showed that body mass index (BMI) of females was positively associated with the RR for the effect of probiotics on GDM (coefficient = 0.084, P = 0.01). The results of subgroup analyses also suggested that probiotics significantly reduced the risk of GDM in women with BMI < 26 kg/m2, but not in those with BMI ≥ 26 kg/m2 (P for subgroup difference = 0.001). In addition, the preventative efficacy of probiotics on GDM was remarkable in women < 30 years, but not in those ≥ 30 years (P for subgroup difference < 0.001). In conclusion, probiotics may be effective in reducing the risk of GDM, particularly for females with lower BMI and younger age.

Detection of iodixanol-induced allergic reaction signals in Chinese inpatients: a multi-center retrospective database study using prescription sequence symmetry analysis.

Objective: This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection. Methods: A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method. Results: 126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories-calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines-as marker drugs. With time intervals of 3, 7, and 28 days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08-2.15), 1.70 (95% CI: 1.68-1.73), 3.85 (95% confidence interval [CI]: 3.75-2.30), 2.30 (95% CI: 2.26-2.35), and 1.95 (95% CI: 1.89-2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%-3%), calcium gluconate (0.19%-0.52%), adrenergic/dopaminergic agents (2.20%-3.37%), glucocorticoids (3.13%-3.76%), and antihistamines (1.05%-1.32%). Conclusion: This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.

Characterising the motion and cardiorespiratory interaction of preterm infants can improve the classification of their sleep state.

AIM: This study aimed to classify quiet sleep, active sleep and wake states in preterm infants by analysing cardiorespiratory signals obtained from routine patient monitors. METHODS: We studied eight preterm infants, with an average postmenstrual age of 32.3 ± 2.4 weeks, in a neonatal intensive care unit in the Netherlands. Electrocardiography and chest impedance respiratory signals were recorded. After filtering and R-peak detection, cardiorespiratory features and motion and cardiorespiratory interaction features were extracted, based on previous research. An extremely randomised trees algorithm was used for classification and performance was evaluated using leave-one-patient-out cross-validation and Cohen's kappa coefficient. RESULTS: A sleep expert annotated 4731 30-second epochs (39.4 h) and active sleep, quiet sleep and wake accounted for 73.3%, 12.6% and 14.1% respectively. Using all features, and the extremely randomised trees algorithm, the binary discrimination between active and quiet sleep was better than between other states. Incorporating motion and cardiorespiratory interaction features improved the classification of all sleep states (kappa 0.38 ± 0.09) than analyses without these features (kappa 0.31 ± 0.11). CONCLUSION: Cardiorespiratory interactions contributed to detecting quiet sleep and motion features contributed to detecting wake states. This combination improved the automated classifications of sleep states.

Revision of the genus Nephelobotys Munroe & Mutuura, 1970 (Lepidoptera, Crambidae, Pyraustinae).

The genus Nephelobotys Munroe & Mutuura, 1970 is revised to include eight species. Three species, N. apiculata sp. nov., N. semicircularis sp. nov. and N. brevis sp. nov. are described as new to science. Two new combinations, N. habisalis (Walker, 1859) comb. nov. and N. flavicilialis (Snellen, 1890) comb. nov., are proposed. N. forcipatusKo & Bae, 2022 syn. nov. is found to be identical with N. habisalis (Walker, 1859). Diagnoses for all species are provided, with illustrations of external features and genitalia.

Genetic dissection and identification of stripe rust resistance genes in the wheat cultivar Lanhangxuan 121, a cultivar selected from a space mutation population.

Stripe rust is a devastating disease of wheat worldwide. Chinese wheat cultivar Lanhangxuan 121 (LHX121), selected from an advanced line L92-47 population that had been subjected to space mutation breeding displayed a consistently higher level of resistance to stipe rust than its parent in multiple field environments. The aim of this research was to establish the number and types of resistance genes in parental lines L92-47 and LHX121 using separate segregating populations. The first population developed from a cross between LHX121 and susceptible cultivar Xinong 822 comprised 278 F2:3 lines. The second validation population comprised 301 F2:3 lines from a cross between L92-47 and susceptible cultivar Xinong 979. Lines of two population were evaluated for stripe rust response at three sites during the 2018-2020 cropping season. Affymetrix 660 K SNP arrays were used to genotype the lines and parents. Inclusive composite interval mapping detected QTL QYrLHX.nwafu-2BS, QYrLHX.nwafu-3BS, and QYrLHX.nwafu-5BS for resistance in all three environments. Based on previous studies and pedigree information, QYrLHX.nwafu-2BS and QYrLHX.nwafu-3BS were likely to be Yr27 and Yr30 that are present in the L92-47 parent. QYrLHX.nwafu-5BS (YrL121) detected only in LHX121 was mapped to a 7.60 cM interval and explained 10.67-22.57% of the phenotypic variation. Compared to stripe rust resistance genes previously mapped to chromosome 5B, YrL121 might be a new adult plant resistance QTL. Furthermore, there were a number of variations signals using 35 K SNP array and differentially expressed genes using RNA-seq between L92-47 and LHX121 in the YrL121 region, indicating that they probably impair the presence and/or function of YrL121. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01461-0.

Rapid cycle deliberate practice: application in forceps simulation training for gynecology and obstetrics residents.

BACKGROUND: Rapid Cycle Deliberate Practice (RCDP) has gained prominence in recent years as an innovative teaching method in simulation-based training for adult and pediatric emergency medical skills. However, its application in the training of forceps delivery skills among obstetrics and gynecology residents remains unexplored. This study aimed to assess the impact of RCDP in this domain. METHODS: Conducted in March 2021, this randomized controlled study involved 60 second-year obstetrics and gynecology residents undergoing standardized training. Participants were randomly assigned to the RCDP group or the traditional teaching method (TTM) group, each comprising 30 residents. The RCDP group followed the RCDP practice mode, while the TTM group adhered to conventional simulation teaching. Post-training assessment of operational proficiency was conducted immediately and after one year. Independent operational confidence and training satisfaction were evaluated through questionnaire surveys and the Satisfaction with Simulation Experience (SSE) scale. Data analysis utilized SPSS 23.0. RESULTS: The RCDP group displayed significantly higher immediate post-training forceps operation scores compared to the TTM group (92.00 [range: 90.00-94.00] vs. 88.00 [range: 86.75-92.00]; z = 3.79; p < .001). However, no significant difference emerged in forceps operation scores after one year (86.00 [range: 85.00-88.00] vs. 85.50 [range: 84.00-88.25]; z = 0.54; p = .59). The RCDP group exhibited notable performance improvement over the TTM group (z = 3.49; p < .001). Independent operation confidence showed no significant discrepancy (p > .05). Importantly, the RCDP group reported higher satisfaction scores, particularly in the Debriefing and Reflection subscale (44.00 [range: 43.00-45.00] vs. 41.00 [range: 41.50-43.00]; z = 5.24; p < .001), contributing to an overall superior SSE score (z = 4.74; p < .001). CONCLUSIONS: RCDP exhibits immediate efficacy in elevating forceps delivery skills among residents. However, sustained skill enhancement necessitates innovative approaches, while RCDP's value lies in tailored feedback and reflection for enriched medical education.

Rapid Cycle Deliberate Practice (RCDP) demonstrates immediate effectiveness in enhancing forceps delivery skills among obstetrics and gynecology residents, leading to improved immediate performance, which also increased their satisfaction with the teaching process and operational confidence.Long-term skill retention through RCDP appears limited, highlighting the importance of ongoing reinforcement to prevent skill decay and maintain proficiency.

Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults.

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aß42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aß42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aß42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aß pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aß pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aß pathology. Fibrinogen was associated with both cognition and Aß pathology. Aß pathology may be a critical mediator for impacts of fibrinogen on cognition.

Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response.

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.

Azilsartan improves urinary albumin excretion in hypertension mice.

Hypertension is one of the most important risk factors for chronic kidney diseases, leading to hypertensive nephrosclerosis, including excessive albuminuria. Azilsartan, an angiotensin II type 1 receptor blocker, has been widely used for the treatment of hypertension. However, the effects of Azilsartan on urinary albumin excretion in hypertension haven't been reported before. In this study, we investigated whether Azilsartan possesses a beneficial property against albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Compared to the control group, the ANG/HS group had higher blood pressure, oxidative stress, and inflammatory response, all of which were rescued by Azilsartan dose-dependently. Importantly, the ANG/HS-induced increase in urinary albumin excretion and decrease in the expression of occludin were reversed by Azilsartan. Additionally, it was shown that increased fluorescence intensity of FITC-dextran, declined trans-endothelial electrical resistance (TEER) values, and reduction of occludin and krüppel-like factor 2 (KLF2) were observed in ANG/HS-treated human renal glomerular endothelial cells (HrGECs), then prevented by Azilsartan. Moreover, the regulatory effect of Azilsartan on endothelial monolayer permeability in ANG/HS-treated HrGECs was abolished by the knockdown of KLF2, indicating KLF2 is required for the effect of Azilsartan. We concluded that Azilsartan alleviated diabetic nephropathy-induced increase in Uterine artery embolization (UAE) mediated by the KLF2/occludin axis.

Nonreciprocal toroidal dipole resonance and one-way quasi-bound state in the continuum.

Bound states in the continuum (BICs) provide an alternative way of trapping light at nanoscale. Although the last 10 years have witnessed tremendous progress on BICs from fundamentals to applications, nonreciprocal BICs and their potential applications have not been fully exploited yet. In this study, we demonstrated a one-way quasi-BIC by leveraging an all-dielectric magneto-optical (MO) metasurface. We show that the key point for achieving a one-way quasi-BIC is to excite a magnetization-induced leaky resonance. Here we adopt the longitudinal toroidal dipole (TD) resonance characterized by a vortex distribution of head-to-tail magnetic dipoles parallel to the plane of the MO metasurface. We show that, by breaking the time-reversal symmetry, at critical conditions, the TD resonance can be enhanced in the forward channel and perfectly canceled in the time-reversed channel, resulting in a one-way quasi-BIC. The demonstrated phenomena hold significant promise for practical applications such as magnetic field optical sensing, nonreciprocal optical switching, isolation, and modulation.

Nonlinear error analysis of fast optical delay lines.

Optical delay lines have wide applications in terahertz time-domain spectroscopy and optical coherence tomography. In this study, a fast-rotating optical delay line (FRODL) with 24 turntable reflection surfaces was designed. By analyzing the working principle of the FRODL, a mathematical model was established for the nonlinear parameter error of the FRODL delay time. By constructing the polarization Michelson interference system and testing the FRODL structure, the error of actual assembly parameters of the FRODL was approximately 0.015 mm, the actual delay time of the FRODL was greater than 43.5 ps, and the linearity was 99.785%.

Dapagliflozin prevents kidney podocytes pyroptosis via miR-155-5p/HO-1/NLRP3 axis modulation.

Diabetic nephropathy (DN) is a significant clinical microvascular complication associated with diabetes mellitus (DM), and end-stage diabetes giving rise to kidney failure is developing into the major etiological factor of chronic kidney failure. Dapagliflozin is reported to limit podocyte damage in DM, which has proven to protect against renal failure. Mounting evidence has demonstrated that pyroptosis is associated with DM progression. Nevertheless, whether pyroptosis causes DN and the underlying molecular pathways remain obscure. In this study, we aimed to explore the antipyroptotic attributes of dapagliflozin and elucidate the underlying mechanisms of kidney damage in diabetes. In vivo, experiments were conducted in streptozotocin (STZ)-induced type 2 diabetic mice, which were administered dapagliflozin via gavage for 6 weeks. Subsequently, the specific organizational characteristics and expression of pyroptosis-related genes were evaluated. Intragastric dapagliflozin administration markedly reduced renal tissue injury. Meanwhile, dapagliflozin also attenuated the expression level of pyroptosis associated genes, including ASC, cleaved Caspase-1, GSDMD N-termini, NLRP3, IL-18, and IL-1ß in renal tissue of dapagliflozin-treated animals. Similar antipyroptotic effects were observed in palmitic acid (PA)-treated mouse podocytes. We also found that heme oxygenase 1 (HO-1) enhanced the protection of mouse podocyte clone 5 cells (MPC5). Moreover, miR-155-5p inhibition increased pyroptosis in PA-treated MPC5 cells, suggesting that miR-155-5p acts as an endogenous stimulator that increases HO-1 expression and reduces pyroptosis. Hence, our findings imply that dapagliflozin inhibits podocyte pyroptosis via the miR-155-5p/HO-1/NLRP3 axis in DM. Furthermore, dapagliflozin substitution may be regarded as an effective strategy for preventing pyroptosis in the kidney, including a therapeutic option for treating pyroptosis-related DN.

Computational identification of DNA damage-relevant lncRNAs for predicting therapeutic efficacy and clinical outcomes in cancer.

OBJECTIVES: The role of long non-coding RNAs (lncRNAs) in cancer treatment, particularly in modulating DNA repair programs, is an emerging field that warrants systematic exploration. This study aimed to systematically identify the lncRNA regulators that potentially regulate DNA damage response (DDR). METHODS: Using genome-wide mRNA and lncRNA expression profiles of the same tumor patients, we proposed a novel computational framework. This framework performed Gene Set Variation Analysis to calculate DDR pathway enrichment score, which relies on weighting by tumor purity to obtain DDR activity score for each patient. Then, an in-depth differential expression profiling was conducted to identify pathway activity lncRNAs between high- and low-activity groups, utilizing a bootstrap-based randomization method. RESULTS: We comprehensively charted the landscape of DDR-relevant lncRNAs across 23 epithelial-based cancer types. Its effectiveness was validated by assessing the consistency of these lncRNAs within various datasets of the same cancer type (hypergeometric test P < 0.001), examining the expression perturbation of these lncRNAs in response to treatment and demonstrating its application in prioritizing clinically-related lncRNAs. Furthermore, leveraging 820 epithelial ovarian cancer patients from four public datasets, we applied these lncRNAs identified by DDRLnc to establish and validate a risk stratification model to evaluate the benefits of platinum-based adjuvant chemotherapy for the improvement of clinical treatment outcomes. CONCLUSIONS: Comprehensive pan-cancer analysis illustrates the utility of computational framework in identifying potentially lncRNAs involved in DDR, thereby offering novel insights into the complex realm of cancer research, and it will become a valuable tool for identifying potential therapeutic targets for cancer.