Stability of gross primary productivity and its sensitivity to climate variability in China.

Identifying the stability and sensitivity of land ecosystems to climate change is vital for exploring nature-based solutions. However, the underlying mechanisms governing ecosystem stability and sensitivity, especially in regions with overlapping ecological projects, remain unclear. based on Mann-Kendall, stability analysis method, and multiple regression method, this study quantified the stability and sensitivity of gross primary productivity (GPP) to climate variables [temperature, vapor pressure deficit (VPD), soil moisture, and radiation] in China from 1982 to 2019. Our findings revealed the following: (1) GPP demonstrated an increased trend with lower stability in Eastern regions, whereas a decreasing trend with higher stability was observed in Western and Southwest China. Notably, the stability of GPP was highest (74.58%) in areas with five overlapping ecological projects: Grain to Green, Natural Forest Resource Protection Project, Three-River Ecological Conservation and Restoration Project, Return Grazing to Grassland Project, and Three-North Shelter Forestation Project. (2) In regions with minimal or no overlapping ecological projects, temperature and radiation jointly dominated GPP variations. In contrast, water-related factors (VPD and soil moisture) significantly affected GPP in areas with multiple overlapping ecological projects. (3) In the southwestern and northeastern regions, GPP exhibited the highest sensitivity to climate change, whereas, in the eastern coastal areas and Tibet, GPP showed low sensitivity to climate change. In the Loess Plateau, where five ecological projects overlap extensively, carbon sinks primarily demonstrate a monotonic increasing trend, high stability, and low sensitivity to climate change. This study aimed to assess the stability of the land ecosystems and delineate their sensitivity to climate changes, thereby laying the groundwork for understanding ecosystem resilience.

The Influence of Grain Size on Microstructure Evolution in CeO2 under Xenon Ion Irradiation.

Large-grained UO2 is considered a potential accident-tolerant fuel (ATF) due to its superior fission gas retention capabilities. Irradiation experiments for cerium dioxide (CeO2), used as a surrogate fuel, is a common approach for evaluating the performance of UO2. In this work, spark plasma sintered CeO2 pellets with varying grain sizes (145 nm, 353 nm, and 101 µm) and a relative density greater than 93.83% were irradiated with 4 MeV Xe ions at a fluence of 2 × 1015 ions/cm2 at room temperature, followed by annealing at 600 °C for 3 h. Microstructure, including dislocation loops and bubble morphology of the irradiated samples, has been characterized. The average size of dislocation loops increases with increasing grain size. Large-sized dislocation loops are absent near the grain boundary because the boundary absorbs surrounding defects and prevents the dislocation loops from coalescing and expanding. The distribution of bubbles within the grain is uniform, whereas the large-sized and irregularly shaped xenon bubbles observed in the small grain exhibit pipe diffusion along the grain boundaries. The bubble diameter in the large-grained pellet is the smallest. As the grain size increases, the volumetric swelling of the irradiated pellets decreases while the areal density of Xe bubbles increases. Elemental segregation, which tends to occur at dislocation loops and grain boundaries, has been analyzed. Large-grained CeO2 pellet with lower-density grain boundaries exhibits better resistance to volumetric swelling and elemental segregation, suggesting that large-grained UO2 pellets could serve as a potential ATF.

Outdoor light at night, air pollution and risk of incident type 2 diabetes.

BACKGROUND: Air pollution and outdoor light at night (LAN) have been reported to be related to type 2 diabetes (T2D). However, their interaction with risk of T2D remains uncertain. Therefore, our study aimed to explore the relationship between outdoor LAN, air pollution and incident T2D. METHODS: Our study included a cohort of 24,147 subjects recruited from 2015 to 2018 in Ningbo, China. Land use regression models were used to evaluate particulate matter with a diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2). Satellite images data with a spatial resolution of 500m was used to estimate outdoor LAN levels. T2D new cases were identified by medical records based on health information system. Cox proportional hazards models were used to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we investigated the multiplicative and additive interactions between air pollution and outdoor LAN. RESULTS: During 108,908 person-years of follow-up period, 1016 T2D incident cases were identified. The HRs (95% CIs) were 1.22 (1.15, 1.30) for outdoor LAN, 1.20 (1.00, 1.45) for PM2.5, 1.23 (1.11, 1.35) for PM10 and 1.19 (1.04, 1.37) for NO2 in every interquartile range increase, respectively. Furthermore, significant interactions were observed between outdoor LAN and NO2. CONCLUSIONS: Our findings indicated that air pollution and outdoor LAN were positively associated with T2D. Moreover, we observed an interaction between outdoor LAN and NO2 suggesting that stronger associations for outdoor LAN and T2D in areas with higher levels of NO2, and for NO2 and T2D in areas with higher levels of outdoor LAN.

Genetically predicted frailty index and risk of chronic kidney disease.

Previous findings have reported the association between frailty and chronic kidney disease. However, the causality remains ambiguous. This study aimed to determine whether frailty index is causally associated with chronic kidney disease. We obtained the frailty genome-wide association study (GWAS) data and chronic kidney disease GWAS data from the FinnGen R5 (total n = 216,743; case = 3902, control = 212,841) as the exposure and outcome, respectively. A two-sample Mendelian randomization (MR) analysis was primarily conducted using the inverse-variance weighted (IVW), weighted median and MR-Egger regression analyses. Multivariable MR analysis (MVMR) was conducted for additional adjustment. In the two-sample Mendelian randomization analyses, a total of 14 single nucleotide polymorphisms (SNPs) were recognized as effective instrumental variables. The IVW method showed evidence to support a causal association between frailty index and chronic kidney disease (beta = 1.270; 95% CI 0.608 to 1.931; P < 0.001). MR-Egger revealed a causal association between frailty index and chronic kidney disease (beta = 3.612; 95% CI 0.805 to 6.419; P = 0.027). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = - 0.053; P = 0.119). The weighted median approach and weighted mode method also demonstrated a causal association between frailty index and chronic kidney disease (beta = 1.148; 95% CI 0.278 to 2.019; P = 0.011; beta = 2.194; 95% CI 0.598 to 3.790; P = 0.018). Cochran's Q test and the funnel plot indicated no directional pleiotropy. MVMR analysis revealed that the causal association between frailty index and chronic kidney disease remained after adjusting for potential confounders, body-mass index, inflammatory bowel disease, waist-hip ratio, and C-reactive protein. Our study provides evidence of causal association between frailty and chronic kidney disease from genetic perspectives.

Characterization of kilovoltage x-ray image guidance system with a novel post-processing algorithm on a new slip ring-mounted radiotherapy system.

PURPOSE: This study evaluates the performance of a kilovoltage x-ray image-guidance system equipped with a novel post-processing optimization algorithm on the newly introduced TAICHI linear accelerator (Linac). METHODS: A comparative study involving image quality tests and radiation dose measurements was conducted across six scanning protocols of the kV-cone beam computed tomography (CBCT) system on the TAICHI Linac. The performance assessment utilized the conventional Feldkamp-Davis-Kress (FDK) algorithm and a novel Non-Local Means denoising and adaptive scattering correction (NLM-ASC) algorithm. Image quality metrics, including spatial resolution, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR), were evaluated using a Catphan 604 phantom. Radiation doses for low-dose and standard protocols were measured using a computed tomography dose index (CTDI) phantom, with comparative measurements from the Halcyon Linac's iterative CBCT (iCBCT). RESULTS: The NLM-ASC algorithm significantly improved image quality, achieving a 300%-1000% increase in CNR and SNR over the FDK-only images and it also showed a 100%-200% improvement over the iCBCT images from Halcyon's head protocol. The optimized low-dose protocols yielded higher image quality than the standard FDK protocols, indicating potential for reduced radiation exposure. Clinical implementation confirmed the TAICHI system's utility for precise and adaptive radiotherapy. CONCLUSION: The kV-IGRT system on the TAICHI Linac, with its novel post-processing algorithm, demonstrated superior image quality suitable for routine clinical use, effectively reducing image noise without compromising other quality metrics.

Individual curved-needle interstitial template created using three-dimensional printing for brachytherapy for distal parauterine tumor recurrence.

BACKGROUND: Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three-dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes. PURPOSE: This study aimed to introduce an individual curved-needle interstitial template (ICIT) created using 3D printing technology for high-dose-rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented. METHODS: Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D-printed according to the high-risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V100, V200, D90, and D98) and organs at risk (OARs) (D2cc) were recorded. RESULTS: All patients completed interstitial brachytherapy treatment with the 3D-printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center. CONCLUSION: The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility.

Multiplex Profiling of miR-122 for Preclinical and Clinical Evaluation of Drug-Induced Liver Injury by a Full-Scale Platform.

Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence in situ hybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.

ALDH2 regulates mesenchymal stem cell senescence via modulation of mitochondrial homeostasis.

Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and aging-related diseases, its role in the regulation of human mesenchymal stem cell (MSC) senescence has not been investigated. This study aimed to determine the role of ALDH2 in regulating MSC senescence and illustrate the potential mechanisms. MSCs were isolated from young (YMSCs) and aged donors (AMSCs). Senescence-associated ß-galactosidase (SA-ß-gal) staining and Western blotting were used to assess MSC senescence. Reactive oxygen species (ROS) generation and mitochondrial membrane potential were determined to evaluate mitochondrial function. We showed that the expression of ALDH2 increased alongside cellular senescence of MSCs. Overexpression of ALDH2 accelerated YMSC senescence whereas down-regulation alleviated premature senescent phenotypes of AMSCs. Transcriptome and biochemical analyses revealed that an elevated ROS level and mitochondrial dysfunction contributed to ALDH2 function in MSC senescence. Using molecular docking, we identified interferon regulatory factor 7 (IRF7) as the potential target of ALDH2. Mechanistically, ectopic expression of ALDH2 led to mitochondrial dysfunction and accelerated senescence of MSCs by increasing the stability of IRF7 through a direct physical interaction. These effects were partially reversed by knockdown of IRF7. These findings highlight a crucial role of ALDH2 in driving MSC senescence by regulating mitochondrial homeostasis, providing a novel potential strategy against human aging-related diseases.

The 'queen of the Andes' (Puya raimondii) is genetically fragile and fragmented: a consequence of long generation time and semelparity?

Understanding how life history shapes genetic diversity is a fundamental issue in evolutionary biology, with important consequences for conservation. However, we still have an incomplete picture of the impact of life history on genome-wide patterns of diversity, especially in long-lived semelparous plants. Puya raimondii is a high-altitude semelparous species from the Andes that flowers at 40-100 years of age. We sequenced the whole genome and estimated the nucleotide diversity of 200 individuals sampled from nine populations. Coalescent-based approaches were then used to infer past population dynamics. Finally, these results were compared with results obtained for the iteroparous species, Puya macrura. The nine populations of P. raimondii were highly divergent, highly inbred, and carried an exceptionally high genetic load. They are genetically depauperate, although, locally in the genome, balancing selection contributed to the maintenance of genetic polymorphism. While both P. raimondii and P. macrura went through a severe bottleneck during the Pleistocene, P. raimondii did not recover from it and continuously declined, while P. macrura managed to bounce back. Our results demonstrate the importance of life history, in particular generation time and reproductive strategy, in affecting population dynamics and genomic variation, and illustrate the genetic fragility of long-lived semelparous plants.

Leveraging the intratumoral microbiota to treat human cancer: are engineered exosomes an effective strategy?

Cancer remains a leading cause of global mortality. The tumor microbiota has increasingly been recognized as a key regulator of cancer onset and progression, in addition to shaping tumor responses to immunotherapy. Microbes, including viruses, bacteria, fungi, and other eukaryotic species can impact the internal homeostasis and health of humans. Research focused on the gut microflora and the intratumoral microbiome has revolutionized the current understanding of how tumors grow, progress, and resist therapeutic interventions. Even with this research, however, there remains relatively little that is known with respect to the abundance of microbes and their effects on tumors and the tumor microenvironment. Engineered exosomes are a class of artificial extracellular nanovesicles that can actively transport small molecule drugs and nucleic acids, which have the broad prospects of tumor cell therapy. The present review offers an overview of recent progress and challenges associated with the intratumoral microbiome and engineered exosomes in the context of cancer research. These discussions are used to inform the construction of a novel framework for engineered exosome-mediated targeted drug delivery, taking advantage of intratumoral microbiota diversity as a strategic asset and thereby providing new opportunities to more effectively treat and manage cancer in the clinic.

Association between dietary intake of niacin and stroke in the US residents: evidence from national health and nutrition examination survey (NHANES) 1999-2018.

Objective: This study aims to explore the association between niacin intake and stroke within a diverse, multi-ethnic population. Methods: A stringent set of inclusion and exclusion criteria led to the enrollment of 39,721 participants from the National Health and Nutrition Examination Survey (NHANES). Two interviews were conducted to recall dietary intake, and the USDA's Food and Nutrient Database for Dietary Studies (FNDDS) was utilized to calculate niacin intake based on dietary recall results. Weighted multivariate logistic regression was employed to examine the correlation between niacin and stroke, with a simultaneous exploration of potential nonlinear relationships using restricted cubic spline (RCS) regression. Results: A comprehensive analysis of baseline data revealed that patients with stroke history had lower niacin intake levels. Both RCS analysis and multivariate logistic regression indicated a negative nonlinear association between niacin intake and stroke. The dose-response relationship exhibited a non-linear pattern within the range of dietary niacin intake. Prior to the inflection point (21.8 mg) in the non-linear correlation between niacin intake and stroke risk, there exists a marked decline in the risk of stroke as niacin intake increases. Following the inflection point, the deceleration in the decreasing trend of stroke risk with increasing niacin intake becomes evident. The inflection points exhibit variations across diverse populations. Conclusion: This investigation establishes a negative nonlinear association between niacin intake and stroke in the broader American population.

Holistic investigation of the anti-wrinkle and repair efficacy of a facial cream enriched with C-xyloside.

OBJECTIVE: To investigate the repairing and anti-wrinkle efficacy of the facial cream enriched with C-xyloside, aiming at comprehensively evaluating its skin anti- aging effect and clarify its potential mechanism of action. METHODS: The repairing efficacy was studied on 3D epidermis skin model and the antiaging efficacy was studied on ex-vivo human skin. Two clinical studies were conducted with Chinese females. In the first study, 49 subjects aged between 30 and 50 with wrinkle concerns were recruited and instructed to apply the investigational cream containing C-xyloside for 8 weeks. Wrinkles attributes were assessed by dermatologist. Instrumental measurements on skin hydration, trans-epidermal water loss (TEWL), and skin elasticity were also conducted. In the second study, 30 subjects aged between 25 and 60 with self-declared sensitive skin and facial redness were recruited and instructed to apply the cream for 4 weeks. Biomarker analysis of the stratum corneum was conducted through facial tape strips. RESULTS: The cream improved the histomorphology of the 3D epidermis skin model after SLS stimulation, and significantly increase the expression of LOR and FLG. On human skin, the cream improved the histopathology induced by UV, and significantly increased the protein content of COL I and COL III, collagen density and the number of Ki-67 positive cell of skin compared with model group (n = 3, p < 0.01). The results from the first clinical study demonstrate a significant increased the skin hydration and elasticity by 21.90%, 13.08% (R2) and 12.30% (R5), respectively (n = 49, p < 0.05), and the TEWL values decreased by 33.94% (n = 49, p < 0.05), after 8 weeks application of the cream. In addition, the scores for nasolabial folds, glabellar wrinkle, underneath eye wrinkles, crow's feet wrinkle and forehead wrinkle in the volunteers exhibited a significant reduction of 34.02%, 43.34%, 50.03%, 33.64% and 55.81% respectively (n = 49, p < 0.05). The (rCE)/(fCE) ratio of volunteers based on tape stripping significant increased after using the sample cream (n = 30, p < 0.05). CONCLUSION: The cream containing C-xyloside showed improvement of skin wrinkles and enhancement of skin barrier function. These efficacies may be attributed to the fact that the sample cream can increase the expression of skin barrier related proteins LOR and FLG, promote the maturation of cornified envelope, enhance collagen I and III protein expression and stimulate skin cell proliferation, to provide sufficient evidence supporting its antiaging efficacy of skin.

Conserved features and diversity attributes of chimeric RNAs across accessions in four plants.

As a non-collinear expression form of genetic information, chimeric RNAs increase the complexity of transcriptome in diverse organisms. Although chimeric RNAs have been identified in plants, few common features have been revealed. Here, we systemically explored the landscape of chimeric RNAs across multi-accession and multi-tissue using pan-genome and transcriptome data of four plants: rice, maize, soybean, and Arabidopsis. Among the four species, conserved characteristics of breakpoints and parental genes were discovered. In each species, chimeric RNAs displayed a high level of diversity among accessions, and the clustering of accessions using chimeric events was generally concordant with clustering based on genomic variants, implying a general relationship between genetic variations and chimeric RNAs. Through mass spectrometry, we confirmed a fusion protein OsNDC1-OsGID1L2 and observed its subcellular localization, which differed from the original proteins. Phenotypic cues in transgenic rice suggest the potential functions of OsNDC1-OsGID1L2. Moreover, an intriguing chimeric event Os01g0216500-Os01g0216900, generated by a large deletion in basmati rice, also exists in another accession without the deletion, demonstrating its convergence in evolution. Our results illuminate the characteristics and hint at the evolutionary implications of plant chimeric RNAs, which serve as a supplement to genetic variations, thus expanding our understanding of genetic diversity.

Effect of Serum IL-6 Levels on the Progression of Non-Target Lesions in Patients after Coronary Stenting.

Background: percutaneous coronary intervention (PCI) has become the mainstay of treatment for atherosclerotic cardiovascular disease (ASCVD). Inflammatory factors have been shown to be involved in the initiation and progression of ASCVD. After PCI, the persistence of inflammation, especially the inflammation released at the target lesion, may affect the stability of non-target lesion plaques. Interleukin-6 (IL-6) is one of the most common inflammatory factors, however studies about the influence of IL-6 on the progression of non-target lesions (NTLs) of coronary artery are limited. This study investigated whether serum IL-6 levels can affect the progression of NTLs after coronary stent implantation. Methods: We performed a retrospective cohort study including 441 patients undergoing coronary angiography (CAG) and stent implantation, who had at least one NTL, between January 2019 and December 2021. They underwent followup CAG 9 to 12 months after PCI. Quartile grouping was based on serum IL-6 levels following readmission. The relationship between serum IL-6 levels and the progression of NTLs after coronary stent implantation was analyzed by using logistic regression analysis and restricted cubic spline regression. Predictive value of IL-6 on NTL progression was evaluated using the receiver operating characteristic (ROC) curve. Results: When compared to the first quartile (Q1) group, the probability of NTL progression was increased in Q2 (adjusted odds ratio (aOR) 3.06, 95% CI 1.29-7.29), Q3 (aOR 3.55, 95% CI 1.52-8.26), and Q4 group (aOR 7.51, 95% CI 3.30-17.05), with a trend test p < 0.001. With the increase of IL-6 levels, the risk of progression of NTLs gradually increased, and there was a non-linear relationship between IL-6 and progression of NTLs (p < 0.001). The ROC curve showed that the critical value of the serum IL-6 level was 12.652 pg/mL (area under the curve is 0.673, sensitivity is 54.5%, specificity is 70.9%, p < 0.05). Conclusions: A high serum IL-6 level is an independent risk factor for the progression of NTLs after coronary stent implantation, and has certain predictive value for the progression of NTLs.

Prophylactic norepinephrine infusion to treat hypotension after spinal anaesthesia during caesarean section: a meta-analysis.

BACKGROUND: Spinal anaesthesia is a common anaesthetic method for caesarean sections but often results in hypotension, posing potential risks to maternal and neonatal health. Norepinephrine, as a vasopressor, may be effective in preventing and treating this hypotension. This systematic review and meta-analysis aims to systematically evaluate the efficacy and safety of prophylactic norepinephrine infusion for the treatment of hypotension following spinal anaesthesia in caesarean sections. METHODS: Literature searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases for relevant studies on prophylactic administration of norepinephrine for the treatment of hypotension after spinal anaesthesia in caesarean delivery. Reference lists of included articles were also searched. The latest search update was on March 20, 2024. Meta-analysis was conducted using R software. The methods recommended by the Cochrane Handbook, Begge's and Egger's tests were used for risk of bias evaluation of the included literature. RESULTS: Nine studies were finally included in this study. The results showed that prophylactic administration of norepinephrine was superior to the control group in four aspects of treating hypotension after spinal anaesthesia in caesarean delivery: the incidence of hypotension was reduced [RR = 0.34, 95%CI (0.27-0.43), P < 0.01]; the incidence of severe hypotension was reduced [RR = 0.32, 95%CI (0.21-0.51), P < 0.01]; and maternal blood pressure was more stable with MDPE [MD = -5.00, 95%CI (-7.80--2.21), P = 0.06] and MDAPE [MD = 4.11, 95%CI (1.38-6.85), P < 0.05], the incidence of nausea and vomiting was reduced [RR = 0.52, 95%CI (0.35-0.77), P < 0.01]. On the other hand, the incidence of reactive hypertension was higher than the control group [RR = 3.58, 95%CI (1.94-6.58), P < 0.01]. There was no difference between the two groups in one aspects: newborn Apgar scores [MD = -0.01, 95%CI (-0.10-0.09, P = 0.85)]. CONCLUSION: Prophylactic administration of norepinephrine is effective in treating hypotension after spinal anaesthesia in caesarean delivery patients; however, it does not provide improved safety and carries a risk of inducing reactive hypertension.

Hypotension, or low blood pressure, after spinal anaesthesia can threaten the health of both mothers and their babies during caesarean sections. Norepinephrine is a drug that affects heart rate less and does not easily cross the placental barrier, which may reduce its potential negative effects on the baby. However, there are not many studies on using norepinephrine as a preventive measure. Our study systematically evaluated the use of prophylactic norepinephrine infusion to prevent hypotension in caesarean section patients. We found that it is effective in preventing low blood pressure but does not show improved safety and carries some risk of causing high pressure as a reaction.

Whole transcriptome sequencing indicated the Anti-tumor immunity of NLRP3 in breast cancer.

Breast cancer (BC) is a prevalent cancer of the female reproductive system and a major contributor to cancer-related mortality. The activation of NLRP3, a key inflammasome, has been extensively associated with tumor-related molecular and cellular processes; however, the regulatory mechanisms and specific role of NLRP3 in breast cancer remain incompletely elucidated. This study aimed to evaluate the molecular mechanisms of NLRP3-related genes in BC. Utilizing bioinformatics methods, the present research analyzed the TCGA-BRCA dataset, which included four groups of transcriptome sequencing data as follows, normal (WT), NLRP3 knockout (KO), non-knockout-BRCA (BC-WT), and NLRP3-knockout-BRCA (BC-KO). Results indicated that NLRP3 was significantly down-regulated in TCGA-BRCA. Key module genes were mainly enriched in leukocyte cell-cell adhesion and cytokine-cytokine receptor interaction. Moreover, correlation analysis showed that NLRP3 was positively associated with cancer-associated fibroblasts and negatively associated with CD4+ Th1 T-cells. In addition, the DEGs1 and DEGs2 overlapping indicated 505 feature genes, with Chac1 (negative) and Ugt8a (positive) had the strongest correlation with differential immune cells (class-switched memory B cells). Pathway intersection revealed 13 co-KEGG pathways. The BC-KO group indicated markedly reduced levels of four genes (Ccl19, Ccl20, Ccl21a, and H2-Oa) and increased levels of two genes (Il2ra and H2-Ob). This study delved into the role of NLRP3 in BC, exploring its regulatory mechanisms and the impact gene knockout. Bioinformatics approaches identified NLRP3-associated genes, their enriched pathways, and interactions within the tumor microenvironment (TME), providing novel insights into NLRP3 function, TME dynamics, and potential targets for BC prevention and treatment.

A dosimetric comparison of brachytherapy sources for endometrial cancer: an electronic brachytherapy and an iridium-192 source with multichannel cylinders and a three-dimensional technique.

BACKGROUND AND PURPOSE: Ir192 vaginal brachytherapy (IBT) is commonly used for patients with postoperative endometrial cancer (EC). We devised a novel multichannel vaginal applicator that could be equipped with an electronic brachytherapy (EBT) device. We aimed to explore the differences in physical parameters between the EBT and IBT. MATERIALS AND METHODS: This retrospective study included 20 EC patients who received adjuvant IBT from March 1, 2023, to May 1, 2023. Multichannel vaginal cylinders were used, and three-dimensional plans were generated. We designed an electronic multichannel vaginal applicator model and simulated a three-dimensional EBT plan. In order to ensure comparability, D90 of the CTV for the EBT plan was normalized to be equivalent to that of the IBT plan for the same patient. RESULTS: Twenty EBT plans were compared with 20 IBT plans. Results showed, the mean D90 value of clinical target volume (CTV) was 536.1 cGy for both treatment plans. For the mean dose of CTV, the EBT was significantly greater (738.3 vs. 684.3 cGy, p = 0.000). There was no significant difference in CTV coverage between the EBT and IBT plans. For high-dose areas (V200% and V150%), the EBTs were significantly greater. There were no significant differences in the maximum doses to the vaginal mucosa between the EBT and IBT, whether at the apex or in the middle segment. For the bladder and rectum, both the low-dose area and high-dose area were significantly lower in the EBT plans. For the conformity index, there was no significant difference between the EBT and IBT plans. For the dose homogeneity index, the EBT value was lower. CONCLUSION: In conclusion, under the premise of a three-dimensional brachytherapy plan, for patients receiving multichannel vaginal applicator brachytherapy, compared with IBT, EBT could reduce the dose to the surrounding organs at risk while maintaining the dose in the target area.

Comparative Effectiveness of Interventional Therapy versus Exercise Rehabilitation in Stable Angina Patients with Severe Coronary Artery Stenosis.

Background: Management strategies for stable angina include pharmacotherapy, revascularization, and exercise-based cardiac rehabilitation (CR). The optimal treatment for stable angina patients with severe coronary artery stenosis remains unclear. This study aimed to compare interventional therapy with exercise rehabilitation in this population. Methods: Fifty stable angina patients with severe coronary stenosis who underwent stent implantation were included in the optimal medical therapy (OMT) plus percutaneous coronary intervention (PCI) group, and 50 patients who did not undergo interventional treatment were included in OMT plus CR group receiving exercise rehabilitation guidance for one year. Cardiovascular composite endpoint events, cardiopulmonary fitness, and quality of life scale scores were assessed after one year. Results: No significant difference in incidence of cardiovascular composite endpoint events was observed between OMT plus PCI group with OMT plus CR group (20.0% vs 14.6%) after one year. Cardiopulmonary fitness represented as peak VO2 (19.2±3.5 vs 17.6±3.2 mL/kg/min), peak load (120±19 vs 108±20 W), and AT (13.5±1.5 vs 12.1±1.3 mL/kg/min) were significantly higher in the rehabilitation group than the intervention group after one year. Both groups showed improvement in their quality of life, but the rehabilitation group improved in more scales. Conclusion: Interventional therapy did not reduce cardiovascular events compared to exercise-based rehabilitation in stable angina patients with severe coronary artery stenosis, but the rehabilitation can improve cardiovascular fitness and quality of life more.

Genomic investigation of 18,421 lines reveals the genetic architecture of rice.

Understanding how numerous quantitative trait loci (QTL) shape phenotypic variation is an important question in genetics. To address this, we established a permanent population of 18,421 (18K) rice lines with reduced population structure. We generated reference-level genome assemblies of the founders and genotyped all 18K-rice lines through whole-genome sequencing. Through high-resolution mapping, 96 high-quality candidate genes contributing to variation in 16 traits were identified, including OsMADS22 and OsFTL1 verified as causal genes for panicle number and heading date, respectively. We identified epistatic QTL pairs and constructed a genetic interaction network with 19 genes serving as hubs. Overall, 170 masking epistasis pairs were characterized, serving as an important factor contributing to genetic background effects across diverse varieties. The work provides a basis to guide grain yield and quality improvements in rice.