Isoliquiritigenin Suppresses Breast Tumor Development by Enhancing Host Antitumor Immunity.

Isoliquiritigen (ISL), a constituent of licorice, has been shown to possess antitumorigenic effects in diverse cancer types. In this study, we observed that ISL suppressed breast tumor development significantly more effectively in immunocompetent mice than in immunocompromised ones. In exploring the cause of such a discrepancy, we detected robust tumor infiltration of CD8[Formula: see text] T lymphocytes in mice treated with ISL, not seen in tumors derived from vehicle-treated mice. Moreover, we found a dramatic reduction in PD-L1 in both experimental breast tumors and cultured breast cancer cells upon ISL treatment. In further experiments, we showed that ISL selectively elevated miR-200c in breast cancer and confirmed that PD-L1 mRNA is the target of miR-200c in both murine and human breast cancer cells. ISL suppression of PD-L1 was functionally linked to miR-200c/ZEB1/2 because (1) ISL diminished ZEB1/2; (2) knockdown of ZEB1/2 led to the disappearance of PD-L1; and (3) miR-200c antagomiR disabled ISL to reduce PD-L1. We found evidence that ISL reduced the level of PD-L1 by simultaneously intercepting the ERK and Src signaling pathways. In agreement with clinical finding that PD-L1 antibodies enhance efficacy of taxane-based therapy, we showed that ISL improved the tumoricidal effects of paclitaxel in an orthopedic murine breast tumor model. This study demonstrates that ISL-led tumor suppression acts through the augmentation of host antitumor immunity.

Exploring the link between chromosomal polymorphisms and reproductive abnormalities.

OBJECTIVE: This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. METHODS: We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. RESULTS: Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. CONCLUSION: Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation.

Designing Zero-Dimensional Cadmium-Based Organic-Inorganic Hybrids: The Role of Halogen Doping in Modulating Multifunctional Properties.

Advances in materials science are increasingly dependent on the development of multifunctional materials capable of improving system efficiency and reducing the environmental impact. In this study, two zero-dimensional (0D) cadmium-based organic-inorganic hybrid materials (BEMPD)2CdBr4 (BEMPD-Br, 1) and (BEMPD)2CdBr2Cl2 (BEMPD-ClBr, 2) (BEMPD = 1-(2-bromoethyl)-1-methylpiperidine) were prepared by halogen doping. Compound 2 is a mixed halide in which there are two halogen sites, Cl and Br, and in a disordered state, which has a regulatory effect on the structural distortion and properties of the compound. The Curie temperatures of compounds 1 and 2 are 348 and 390 K, respectively, and the UV-vis absorption spectra showed that the direct band gaps of compounds 1 and 2 were 4.68 and 4.8 eV, respectively. In addition, room-temperature photoluminescence experiments show broadband emission peaks at 717 and 683 nm for compounds 1 and 2, respectively, with fluorescence lifetimes of 2.414 and 3.915 µs. These 0D hybrids provide an avenue for the development of smart materials and optoelectronic devices, and also provide positive clues for manipulating the properties of organic-inorganic hybrid compounds.

[Spatiotemporal Characteristics and Influencing Factors of the Synergistic Effect of Pollution Reduction and Carbon Reduction in China].

Based on the use of the coupling coordination model to calculate the coupling coordination degree of carbon emission and pollutant control, the national, regional, and provincial spatiotemporal characteristics of the synergistic effect of pollution control and carbon emissions reduction in China were further analyzed, facilitating the crucial to identification of key areas. The fixed effects regression models and provincial panel data from 2006 to 2020 were used to explore factors contributing to better synergizing the reduction of pollution and carbon emissions in China. On this basis, the adjustment variable of R&D investment intensity was introduced, and the regulation effect model was constructed to further explore the influence mechanism of the synergistic effect of pollution reduction and carbon reduction. The results showed that： synergy exists between carbon emission reduction and the air pollution control system, the evolution of the synergistic effect of pollution reduction and carbon reduction in China presented an inverted "U"-shaped trend from 2006 to 2020, and there was spatial aggregation and a spatial spillover effect in pollution reduction and carbon reduction. The synergistic governance of carbon emission and pollutant control was still at a relatively low level. The carbon emission and air pollutant emission systems were still in an unstable and uncoordinated state. The results showed that： The degree of coordination of eastern China, central China, and western China decreased in turn. At the national level, energy consumption structure, per capita GDP, and the proportion of green investment were the main factors affecting the synergistic effect of pollution reduction and carbon. The heterogeneity of the influencing factors existed in the central, eastern, and western regions on industrial structure, energy consumption structure, energy utilization efficiency, per capita GDP, urbanization rate, the proportion of green investment, and transportation structure. The intensity of R&D played a significant moderating effect in the whole country, eastern, and central regions. However, no significant moderating effect was identified in the western region. In the eastern region, the urbanization rate, the proportion of green investment, and the transportation structure could not have a significant effect on the synergistic effect of pollution reduction and carbon reduction alone, and it must be coordinated with the intensity of R&D.

Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations: a functional magnetic resonance imaging study.

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). CONCLUSION: fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

Immobilizing lead in aqueous solution and loess soil using microbially induced carbonate/phosphate precipitation (MICP/MIPP) under harsh pH environments.

The bioaccumulation of heavy metals due to metallurgical and smelting activities threatens human health. Although microbial-induced carbonate/phosphate precipitation (MICP/MIPP) technology has been applied to heavy metal remediation, the relative merits of MICP and MIPP, especially under extreme pH environments, have not yet been documented. In this study, Sporosarcina pasteurii (SP)-based MICP and Bacillus megaterium (BM)-based MIPP were applied to immobilize lead (Pb) in aqueous solution and loess soil. The results showed that the BM retained a strong phosphorolysis ability when under strongly acidic conditions, while the ureolysis ability of SP approached zero. Furthermore, the bioprecipitates obtained under BM-based MIPP had a denser appearance, presumably due to the enrichment of calcite and apatite crystals. The results also showed that Pb immobilization was achieved through bacterial adsorption, the chelate function of sodium glycerophosphate (SGP), large organic matter complexation, and biomineralization through the MICP/MIPP mechanism. Under SP-based MICP, SP and large organic matter immobilized Pb2+ at rates of 17.6 % and 31.7 %, respectively, while under BM-based MIPP, BM, organic matter, and SGP immobilized Pb2+ at rates of 21.5 %, 23.4 %, and 48.5 % respectively. The MICP and MIPP mechanisms dominated Pb immobilization at rates of 78.6 % and 99.6 %, respectively.

Study of condensable particulate matter from stationary combustion sources: Source profiles, emissions, and impact on ambient fine particulate matter.

Although significant progress has been made in controlling emissions from stationary combustion sources in China over the past decade, understanding of condensable particulate matter (CPM) emissions from these sources and their impact on ambient PM2.5 remains limited. In this study, we established the source profiles and emission inventories of CPM from coal-fired industrial boilers (CFIBs), coal-fired power plants (CFPPs), and iron and steel industry (ISIs) for the Yangtze River Delta (YRD) region of China; furthermore, the air quality model (Community Multiscale Air Quality, CMAQ) was used to evaluate the impact of CPM emissions from these three types of stationary combustion sources on ambient PM2.5 during Feb. 2018, a month characterized by elevated PM2.5 concentrations. The results indicated that CPM emissions from these three sources in the YRD region before and after the implementation of the ultra-low emissions (ULE) policy amounted to 109,839 and 43,338 tons, respectively, with particularly high emission intensity along the Yangtze River. The implementation of CFPPs ULE policy was shown to reduce the impact of CPM emissions from these three stationary sources on monthly PM2.5 concentrations from 0.92 µg/m3 to 0.41 µg/m3 (with a maximum of 5.35 µg/m3). This reduction exceeded the 0.31 µg/m3 decrease in PM2.5 concentrations resulting from the emission reductions of conventional pollutants (FPM, SO2 and NOx). CPM emissions from these three stationary sources were found to increase the PM2.5 by 0.68 µg/m3 during pollution periods. The largest components of PM2.5 contributed by CPM emissions from stationary combustion sources were sulfate, organic carbon, and nitrate, accounting for 21.4 %, 21.1 %, and 18.2 %, respectively. Particularly, contributions from CPM emissions to PM2.5 varied by altitude, with a relatively large impact at altitudes between 220 and 460 m. Attention should be given to CPM emission control, with particular priority placed on implementing ULE measures for ISIs and CFIBs.

Studies on the Anti-Inflammatory Effect of Xiaoyao Pills in The Treatment of Postmenopausal Osteoporosis in Mice.

Osteoporosis is a common metabolic disease of elderly and postmenopausal women, with no obvious symptoms during its early stages. In the latter stages of this condition, the patients are prone to fractures, and this can seriously affect their health and quality of life. The worldwide increase in life expectancy has made osteoporosis a global concern. The Xiaoyao pills were previously used in the treatment of depression. In addition, the drug appeared to have estrogen-like activity, which affected the expression of ALP, an early osteoblast-specific marker, and COL-1, a major component of bone extracellular matrix. Xiaoyao pills were assessed for their effects on postmenopausal osteoporosis (PMOM) in mice. The target information of each herbal component of Xiaoyao pills was accessed through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Information from GeneCards, OMIM, PharmGkb, TTD, DrugBank, and other websites was used to construct the regulatory network of the herbal complex through Cytoscape and String network to assess the protein interactions. Mice were ovariectomized, and treated with high and low doses of Xiaoyao pills and these were compared to controls. Their symptoms were assessed by immunocytochemistry of bone tissues. The results suggested that Xiaoyao pills had the ability to alleviate the symptoms of PMOM in ovariectomized mice through the IL-17 signaling pathway. This drug has the potential to become a novel therapeutic agent for the treatment of osteoporosis.

Investigation of guanidino acetic acid and rumen-protected methionine induced improvements in longissimus lumborum muscle quality in beef cattle.

This study examined the impact of dietary guanidino acetic acid (GAA) and rumen-protected methionine (RPM) on beef quality in Simmental bulls. For 140 days, forty-five bulls (453.43 ± 29.05 kg) were randomly divided into control (CON), 0.1% GAA (GAA), and 0.1% GAA + 0.1% RPM (GAM) groups with 15 bulls in each group and containing 3 pen with 5 bulls in each pen. Significant improvements in eye muscle area, pH48h, redness (a*) value, and crude protein (CP) content of longissimus lumborum (LL) muscles were observed in the GAA and GAM groups (P < 0.05). Conversely, the lightness (L*) value, drip loss, cooking loss, and moisture contents decreased (P < 0.05). Additionally, glutathione (GSH) and glutathione peroxidase (GSH-PX) concentrations of LL muscles in GAM were higher (P < 0.05), while malondialdehyde (MDA) content of LL muscles in GAA and GAM groups were lower (P < 0.05). Polyunsaturated fatty acids (PUFA) profiles were enriched in beef from GAM group (P < 0.05). The addition of GAA and RPM affected the expression of genes in LL muscle, such as HMOX1, EIF4E, SCD5, and NOS2, which are related to hypoxia metabolism, protein synthesis, and unsaturated fatty acid synthesis-related signaling pathways. In addition, GAA and RPM also affected the content of a series of metabolites such as L-tyrosine, L-tryptophan, and PC (O-16:0/0:0) involved in amino acid and lipid metabolism-related signaling pathways. In summary, GAA and RPM can improve the beef quality and its nutritional composition. These changes may be related to changes in gene expression and metabolic pathways related to protein metabolism and lipid metabolism in beef.

An additional proofreader contributes to DNA replication fidelity in mycobacteria.

The removal of mis-incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the ε-exonuclease DnaQ is a well-established proofreader in the model organism Escherichia coli, it has been shown that proofreading in a majority of bacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase, despite the presence of a DnaQ homolog that is structurally and functionally distinct from E. coli DnaQ. However, the biological functions of this type of noncanonical DnaQ remain unclear. Here, we provide independent evidence that noncanonical DnaQ functions as an additional proofreader for mycobacteria. Using the mutation accumulation assay in combination with whole-genome sequencing, we showed that depletion of DnaQ in Mycolicibacterium smegmatis leads to an increased mutation rate, resulting in AT-biased mutagenesis and increased insertions/deletions in the homopolymer tract. Our results showed that mycobacterial DnaQ binds to the ß clamp and functions synergistically with the PHP domain proofreader to correct replication errors. Furthermore, the loss of dnaQ results in replication fork dysfunction, leading to attenuated growth and increased mutagenesis on subinhibitory fluoroquinolones potentially due to increased vulnerability to fork collapse. By analyzing the sequence polymorphism of dnaQ in clinical isolates of Mycobacterium tuberculosis (Mtb), we demonstrated that a naturally evolved DnaQ variant prevalent in Mtb lineage 4.3 may enable hypermutability and is associated with drug resistance. These results establish a coproofreading model and suggest a division of labor between DnaQ and PHP domain proofreader. This study also provides real-world evidence that a mutator-driven evolutionary pathway may exist during the adaptation of Mtb.

Pathway-Adapted Biosensor for High-Throughput Screening of O-Methyltransferase and its Application in Vanillin Synthesis.

Vanillin is a widely used flavoring compound in the food, pharmaceutical, and cosmetics area. However, the biosynthesis of vanillin from low-cost shikimic acid is significantly hindered by the low activity of the rate-limiting enzyme, caffeate O-methyltransferase (COMT). To screen COMT variants with improved conversion rates, we designed a biosensing system that is adaptable to the COMT-mediated vanillin synthetic pathway. Through the evolution of aldehyde transcriptional factor YqhC, we obtained a dual-responsive variant, MuYqhC, which positively responds to the product and negatively responds to the substrate, with no response to intermediates. Using the MuYqhC-based vanillin biosensor, we successfully identified a COMT variant, Mu176, that displayed a 7-fold increase in the conversion rate compared to the wild-type COMT. This variant produced 2.38 mM vanillin from 3 mM protocatechuic acid, achieving a conversion rate of 79.33%. The enhanced activity of Mu176 was attributed to an enlarged binding pocket and strengthened substrate interaction. Applying Mu176 to Bacillus subtilis increased the level of vanillin production from shikimic acid by 2.39-fold. Further optimization of the production chassis, increasing the S-adenosylmethionine supply and the precursor concentration, elevated the vanillin titer to 1 mM, marking the highest level of vanillin production from shikimic acid in Bacillus. Our work highlights the significance of the MuYqhC-based biosensing system and the Mu176 variant in vanillin production.

Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

INTRODUCTION: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. MATERIALS AND METHODS: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. RESULTS: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (ß = 0.923;p = 0.031). CONCLUSION: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

The application of proximal tibial anterior closing wedge osteotomy in anterior cruciate ligament reconstruction.

Introduction: Posterior tibial slope (PTS) plays a vital role in knee stability. PTS of more than 12° may be considered with increased strain on the native anterior cruciate ligament (ACL) fibers. To handle the instability caused by changes in PTS degree, Proximal Tibial Anterior Closing Wedge Osteotomy (PT-ACWO) is adopted by surgeons. Methods: Between October 2015 and October 2019, our department conducted a retrospective analysis of patients who experienced anterior cruciate ligament reconstruction (ACLR) graft failures, with a particular focus on pathological PTS. The time from initial ACLR to revision ranged from 1 to 10 years, with a mean of 2.5 years. Radiological assessments of PTS were conducted, and outcomes were quantified using the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The surgical technique and the use of 3D Patient-Specific Instrumentation (PSI) were outlined. Preoperative imaging included the use of Kirschner wires to establish tibial plateau reference points, and 3D-PSI was employed to guide the location and depth of the tibial osteotomy, which was performed obliquely. In a notable instance, a novel tibial tunnel was mapped out, and ortho-bridge system (OBS) fixation was utilized to ensure adequate space for the new tunnel. Results: In a cohort of seven patients with a mean follow-up of 28.1 months, a significant reduction in PTS was noted postoperatively (median [interquartile range, IQR], from 15.27° [13.46°, 16.60°] to 6.25° [5.89°, 6.78°]; P = 0.002). IKDC score improved to 85.10 (80.25, 88.10), P < 0.001; the Lysholm score to 88.00 (73.00, 90.50), P < 0.001; and the Tegner score to 8.00 (7.20, 8.05), P = 0.025 at final follow-up. Skin incision healing delays occurred in two instances, yet achieved closure by six weeks. Radiographs at three months demonstrated faster bone healing in oblique osteotomies than transverse ones. Knee joint stability was maintained, with no additional complications or evidence of instability noted. Magnetic resonance imaging (MRI) confirmed graft integrity in all patients, without signs of enlargement or mispositioning at last observation. Conclusion: An augmented PTS angle exceeding 12 may constitute a potential etiology for the failure of ACLR grafts. In such patients, the implementation of ACLR combined with PT-ACWO could mitigate the risk of surgical failure during initial ACLR or subsequent revision procedures.

Blood trihalomethane and urinary haloacetic acid concentrations in relation to hypertension: An observational study among 1162 healthy men.

Disinfection byproducts (DBPs) have demonstrated cardiovascular and reproductive toxicity. However, the associations and mechanisms of DBP exposure in relation to hypertension among healthy young men, which are critical for gaining new insights into the prevention and treatment of male subfertility, remain unclear. In 2017-2018, we recruited 1162 healthy Chinese men. A single blood sample was collected and measured for trihalomethane (THM) concentrations (n = 956). Up to 2930 repeated urinary samples were collected at baseline and during follow-up periods and determined for haloacetic acid concentrations. Oxidative stress (OS) biomarkers were measured in within-subject pooled urinary samples (n = 1003). In total, 403 (34.68 %) participants were diagnosed with stage 1-2 hypertension (≥130/80 mmHg) and 108 (9.29 %) stage 2 hypertension (≥140/90 mmHg). In adjusted models, blood bromodichloromethane (BDCM) concentrations were positively associated with the risk of stage 1-2 and stage 2 hypertension [ORs= 1.48 (95 % CI: 1.15, 1. 91) and 1.65 (95 % CI: 1.08, 2.51), respectively, per 2.7-fold increase in BDCM concentrations]. Additionally, we found positive associations between DBP exposure biomarkers and urinary concentrations of 4-hydroxy-2-nonenal-mercapturic acid and 8-hydroxy-2-deoxyguanosine. However, these OS biomarkers were unrelated to hypertension. Our results suggest that BDCM exposure may be associated with a greater risk of hypertension among healthy young men.

Piperazine ferulate inhibits diabetic nephropathy by suppressing AGE/RAGE-mediated inflammatory signaling in rats and podocytes.

Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.

Crossmodal hierarchical predictive coding for audiovisual sequences in the human brain.

Predictive coding theory suggests the brain anticipates sensory information using prior knowledge. While this theory has been extensively researched within individual sensory modalities, evidence for predictive processing across sensory modalities is limited. Here, we examine how crossmodal knowledge is represented and learned in the brain, by identifying the hierarchical networks underlying crossmodal predictions when information of one sensory modality leads to a prediction in another modality. We record electroencephalogram (EEG) during a crossmodal audiovisual local-global oddball paradigm, in which the predictability of transitions between tones and images are manipulated at both the stimulus and sequence levels. To dissect the complex predictive signals in our EEG data, we employed a model-fitting approach to untangle neural interactions across modalities and hierarchies. The model-fitting result demonstrates that audiovisual integration occurs at both the levels of individual stimulus interactions and multi-stimulus sequences. Furthermore, we identify the spatio-spectro-temporal signatures of prediction-error signals across hierarchies and modalities, and reveal that auditory and visual prediction errors are rapidly redirected to the central-parietal electrodes during learning through alpha-band interactions. Our study suggests a crossmodal predictive coding mechanism where unimodal predictions are processed by distributed brain networks to form crossmodal knowledge.

Effectiveness Spatiotemporal of Pressure Unloading and Gas Extraction in Remote Upper Protected Seam Mining.

Severe gas hazards are increasing in deep mining areas, and there exists an enormous traditional challenge for protected seam mining. In this work, we conducted a multifaceted investigation into the spatiotemporal effectiveness exerted by pressure unloading from a distant safeguarded stratum in concert with the application of gas extraction methodologies. The stress and displacement evolution in the protected coal seam (PCS) are analyzed by applying Flac3D, and then positives are verified by the measurement of coal seam deformation and investigation of the unloading boundary. The results show that diminution coefficient of 0.62, and record an expansive deformation rate of 5.83%. The opportune temporal window for effective gas drainage is discerned, with its time window spans from 58 to 67 days as the expanse between 350 and 400 m progresses at the working face. Continuous and effective gas extraction occurs when transverse cracks in the PCS reach an optimal state of pressure relief. The final cumulative gas extraction was 320,300 m3 with an extraction efficiency of 34.3%. A residual gas volume of 3.68 m3/t and a residual gas pressure of 0.5 MPa reflect the efficient gas extraction.

Personalized treatment using predictive biomarkers in solid organ malignancies: A review.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

Long-Term Survival Trend of Gynecological Cancer: A Systematic Review of Population-Based Cancer Registration Data.

Gynecological cancer significantly affect the health of women. This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers. We searched PubMed, Embase, Web of Science, SinoMed, and SEER for survival analyses of cancer registration data of cervical, endometrial, and ovarian cancers published between 1980 and 2022. Globally, the highest 5-year observed survival rate for cervical cancer was 76.5% in Anshan, Liaoning, China (2008-2017). The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland (1995-1999, 82.5%) and Singapore (1988-1992, 62.0%). The 5-year relative survival rate of cervical cancer patients was higher in Haining, Zhejiang, China (2011-2014, 85.8%). Korea ranked first at 89.0% and 64.5% for endometrial and ovarian cancers, respectively. Survival rates have improved for cervical, endometrial, and ovarian cancers. Patients aged ≥ 75 years and those with advanced-stage disease had the worst 5-year survival rates. Survival rates were better for squamous cell carcinoma in cervical cancer, for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer, and for germ cell and sex-cord stromal tumors in ovarian cancer. Over the past four decades, the survival rates of gynecological cancers have increased globally, with notable increases in cervical and endometrial cancers. Survival rates are higher in developed countries, with a slow-growing trend. Future studies should focus on improving survival, especially in ovarian cancer patients.