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The linkage between N 2 O emissions and the abundance of nitrifier and denitrifier genes is unclear in the intensively managed calcareous fluvo-aquic soils of the North China Plain. We investigated the abundance of bacterial amoA for nitrification and narG, nirS, nirK , and nosZ for denitrification by in situ soil sampling to determine how the abundance of these genes changes instantly during N fertilization events and is related to high N 2 O emission peaks. We also investigated how long-term incorporated straw and/or manure affect(s) the abundance of these genes based on a seven-year field experiment. The overall results demonstrate that the long-term application of urea-based fertilizer and/or manure significantly enhanced the number of bacterial amoA gene copies leading to high N 2 O emission peaks after N fertilizer applications. These peaks contributed greatly to the annual N 2 O emissions in the crop rotation. A significant correlation between annual N 2 O emissions and narG, nirS , and nirK gene numbers indicates that the abundance of these genes is related to N 2 O emission under conditions for denitrification, thus partly contributing to the annual N 2 O emissions. These findings will help to draw up appropriate measures for mitigation of N 2 O emissions in this ‘hotspot’ region.

The rational for the study was to review the literature on the toxicity and corresponding mechanisms associated with lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As), individually and as mixtures, in the environment. Heavy metals are ubiquitous and generally persist in the environment, enabling them to biomagnify in the food chain. Living systems most often interact with a cocktail of heavy metals in the environment. Heavy metal exposure to biological systems may lead to oxidation stress which may induce DNA damage, protein modification, lipid peroxidation, and others. In this review, the major mechanism associated with toxicities of individual metals was the generation of reactive oxygen species (ROS). Additionally, toxicities were expressed through depletion of glutathione and bonding to sulfhydryl groups of proteins. Interestingly, a metal like Pb becomes toxic to organisms through the depletion of antioxidants while Cd indirectly generates ROS by its ability to replace iron and copper. ROS generated through exposure to arsenic were associated with many modes of action, and heavy metal mixtures were found to have varied effects on organisms. Many models based on concentration addition (CA) and independent action (IA) have been introduced to help predict toxicities and mechanisms associated with metal mixtures. An integrated model which combines CA and IA was further proposed for evaluating toxicities of non-interactive mixtures. In cases where there are molecular interactions, the toxicogenomic approach was used to predict toxicities. The high-throughput toxicogenomics combines studies in genetics, genome-scale expression, cell and tissue expression, metabolite profiling, and bioinformatics.

Results and discussion Ectopic tsRNA signatures in pancreatic cancer serum To explore whether serum tsRNAs could serve as novel biomarkers for PC, we performed preliminary screening by small RNA sequencing followed by qRT-PCR validation on individual basis. Elevated serum tRF-Pro-AGG-004 and tRF-Leu-CAG-002 originate from tumor cells To determine whether the high levels of the two tsRNAs in PC serum were induced by perturbations in PC tissues, we first examined the tissue and paired serum levels of tRF-Pro-AGG-004 and tRF-Leu-CAG-002 from the same patients in a independent clinical cohort (n = 20, Table S4) and observed an positive correlation (Fig. 2A). [...]treatment by two tsRNAs inhibitors in cells showed decreased tsRNAs levels in culture medium (Fig. 2C), suggesting that tsRNAs in culture medium were directly released from PC cells. Traditional pathological staging systems may have reached their limit for predicting outcomes, and new molecular biomarkers may add values. [...]we checked and scored the two-tsRNAs expression in 2 clinical PC cohorts by ISH analysis in standard process.

Background Exposure to cyclophosphamide (CTX) induces premature ovarian insufficiency (POI). Quercetin is a natural flavonoid that exhibits anti-inflammatory and antioxidant properties, and its antioxidant activity is correlated with POI. However, the mechanism underlying its protective role in CTX-induced ovarian dysfunction is unclear. This study aimed to explore whether quercetin can protect ovarian reserves by activating mitochondrial biogenesis and inhibiting pyroptosis. Methods Thirty-six female C57BL/6 mice were randomly subdivided into six groups. Except for the control group, all groups were injected with 90 mg/kg CTX to establish a POI model and further treated with coenzyme 10 or various doses of quercetin. The mice were sacrificed 48 h after 10 IU pregnant mare serum gonadotropin was injected four weeks after treatments. We used enzyme-linked immunosorbent assays to detect serum hormone expression and light and transmission electron microscopy to assess ovarian tissue morphology and mitochondria. Additionally, we tested oxidant and antioxidant levels in ovarian tissues and mitochondrial function in granulosa cells (GCs). The expression of mitochondrial biogenesis and pyroptosis-related proteins and mRNA was analyzed using western blotting and RT-qPCR. Results Quercetin elevated serum anti-Müllerian hormone, estradiol, and progesterone levels, decreased serum follicle-stimulating hormone and luteinizing hormone levels, and alleviated ovarian pathology. It reduced the mitochondrial DNA content and mitochondrial membrane potential. Furthermore, it upregulated ATP levels and the mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), mitochondrial transcription factor A, and superoxide dismutase 2. In addition, it suppressed NOD-like receptor pyrin domain containing 3, caspase-1, interleukin-1β, and gasdermin D levels in the GCs of POI mice. Conclusions Quercetin protected the ovarian reserve from CTX-induced ovarian damage by reversing mitochondrial dysfunction and activating mitochondrial biogenesis via the PGC1-α pathway. Moreover, quercetin may improve ovarian functions by downregulating pyroptosis in the CTX-induced POI model. Thus, quercetin can be considered a potential agent for treating POI.

Chinese medicinal retention enemas have gradually attracted the attention of clinicians as an alternative approach for tubal obstructive infertility. The purpose of this study was to investigate the efficacy and safety of conventional surgery combined with traditional Chinese medicinal retention enemas for the treatment of tubal obstructive infertility. Eight electronic databases were searched from their inception to November 30, 2022. To assess the efficacy and safety of different treatments, following outcomes were measured: clinical pregnancy rate, clinical total effective rate, incidence of ectopic pregnancy, the improvement of Traditional Chinese Medicinal (TCM) symptoms, the improvement of the signs of obstructive tubal infertility and side effects. A total of 23 Randomized Controlled Trials (RCTs) with 1909 patients met the inclusion criteria. The pooled results showed a higher pregnancy rate in the experimental group than in the control group (RR 1.75, 95% CI [1.58, 1.94], Z = 10.55, P<0.00001). The clinical total effective rate in the experimental group was higher than that in the control group (RR 1.28, 95% CI [1.23, 1.34], Z = 11.07, P<0.00001). The incidence of ectopic pregnancy in the experimental group was lower than that in the control group (RR 0.40, 95% CI [0.20, 0.77], Z = -2.73, P = 0.01). Based on current evidence, we concluded that conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility was superior to conventional surgery alone in improving the clinical pregnancy rate, improving clinical total effective rate, improving TCM symptoms, improving the signs of obstructive tubal infertility and lowering the incidence of ectopic pregnancy. However, further clinical trials with high-quality methodologies need to be conducted.

Immune checkpoint blockade therapy has demonstrated promising clinical outcomes for multiple cancer types. However, the emergence of resistance as well as inadequate biomarkers for patient stratification have largely limited the clinical benefits. Here, we showed that tumors with high TYRO3 expression exhibited anti-programmed cell death protein 1/programmed death ligand 1 (anti-PD-1/PD-L1) resistance in a syngeneic mouse model and in patients who received anti-PD-1/PD-L1 therapy. Mechanistically, TYRO3 inhibited tumor cell ferroptosis triggered by anti-PD-1/PD-L1 and facilitated the development of a protumor microenvironment by reducing the M1/M2 macrophage ratio, resulting in resistance to anti-PD-1/PD-L1 therapy. Inhibition of TYRO3 promoted tumor ferroptosis and sensitized resistant tumors to anti-PD-1 therapy. Collectively, our findings suggest that TYRO3 could serve as a predictive biomarker for patient selection and a promising therapeutic target to overcome anti-PD-1/PD-L1 resistance.

The urban heat island (UHI) phenomenon caused by rapid urbanization has become an important global ecological and environmental problem that cannot be ignored. In this study, the UHI effect was quantified using Landsat 8 image inversion land surface temperatures (LSTs). With the spatial scale of street units in Fuzhou City, China, using ordinary least squares (OLS) regression, geographically weighted regression (GWR) models, and multi-scale geographically weighted regression (MGWR), we explored the spatial heterogeneities of the influencing factors and LST. The results indicated that, compared with traditional OLS models, GWR improved the model fit by considering spatial heterogeneity, whereas MGWR outperformed OLS and GWR in terms of goodness of fit by considering the effects of different bandwidths on LST. Building density (BD), normalized difference impervious surface index (NDISI), and the sky view factor (SVF) were important influences on elevated LST, while building height (BH), forest land percentage (Forest_per), and waterbody percentage (Water_per) were negatively correlated with LST. In addition, built-up percentage (Built_per) and population density (Pop_Den) showed significant spatial non-stationary characteristics. These findings suggest the need to consider spatial heterogeneity in analyses of impact factors. This study can be used to provide guidance on mitigation strategies for UHIs in different regions.

Background: High-speed urbanization has brought about a number of ecological and environmental problems, as well as the use of remote sensing to monitor the urban ecological environment and explore the main factors affecting its changes. It is important to promote the sustainable development of cities. Methods: In this study, we quantify the ecological quality of the study area from 2000 to 2020 based on the remote sensing ecological index (RSEI) and analyze its drivers through Geodetector and geographically weighted regression. Results: The RSEI of Fuzhou City from 2000 to 2020 showed an increasing followed by a decreasing trend, with obvious spatial autocorrelation. The main driving factors causing the spatial divergence of the RSEI were elevation (q = 0.48–0.63), slope (0.42–0.59), and GDP (0.3–0.42), and the driving effect and range of each factor changed with time. Conclusion: In this paper, we explore changes in the ecological environment in Fuzhou City over the past 20 years, as well as the scope and magnitude of the drivers, providing an important reference basis to improve the ecological environment quality of the city.

Significance Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and mutations in fused in sarcoma (FUS) cause a subset of familial ALS. Mutant FUS forms cytoplasmic inclusions, but it is unclear whether loss of FUS function in the nucleus or toxicity gained in the cytoplasm is more critical in the ALS etiology. The physiological function of FUS is also uncharacterized. We found that a significant portion of FUS was bound to active chromatin and that ALS mutations dramatically reduced FUS chromatin binding. A high order FUS assembly is mediated by the N-terminal QGSY (glutamine-glycine-serine-tyrosine)-rich region and is required for FUS chromatin binding and the transcription activation by FUS. ALS mutations in FUS can cause its loss of function in the nucleus by disrupting this assembly and chromatin binding. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Fused in sarcoma (FUS) is a DNA/RNA binding protein and mutations in FUS cause a subset of familial ALS. Most ALS mutations are clustered in the C-terminal nuclear localization sequence of FUS and consequently lead to the accumulation of protein inclusions in the cytoplasm. It remains debatable whether loss of FUS normal function in the nucleus or gain of toxic function in the cytoplasm plays a more critical role in the ALS etiology. Moreover, the physiological function of FUS in the nucleus remains to be fully understood. In this study, we found that a significant portion of nuclear FUS was bound to active chromatin and that the ALS mutations dramatically decreased FUS chromatin binding ability. Functionally, the chromatin binding is required for FUS transcription activation, but not for alternative splicing regulation. The N-terminal QGSY (glutamine-glycine-serine-tyrosine)-rich region (amino acids 1–164) mediates FUS self-assembly in the nucleus of mammalian cells and the self-assembly is essential for its chromatin binding and transcription activation. In addition, RNA binding is also required for FUS self-assembly and chromatin binding. Together, our results suggest a functional assembly of FUS in the nucleus under physiological conditions, which is different from the cytoplasmic inclusions. The ALS mutations can cause loss of function in the nucleus by disrupting this assembly and chromatin binding.

Background Nutrition impact symptoms (NIS) are common among cancer patients and influence prognosis. This study aimed to investigate the prognostic significance of NIS in gastric cancer patients using data from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) database. Methods We conducted a retrospective cohort study using data from 2,673 adult patients with confirmed gastric cancer enrolled in the INSCOC database between January 2013 to February 2020. NIS, including appetite loss, vomiting, dysphagia, and early satiety, were assessed using the Patient-Generated Subjective Global Assessment (PG-SGA). Overall survival (OS) was the primary outcome, while quality of life (QoL) was the secondary outcome. Statistical analyses included Kaplan–Meier survival analysis, Cox proportional hazards regression, and propensity score matching (PSM) to reduce confounding. Results Patients with NIS had significantly worse OS compared to those without (median OS: 74.1 vs. 81.3 months, p  < 0.001). In multivariate analysis, NIS was an independent predictor of mortality (HR: 1.28, 95% CI: 1.11–1.48, p  = 0.001). Vomiting and dysphagia were particularly associated with increased mortality (HR: 1.22, p  = 0.038 and HR: 1.80, p  < 0.001, respectively). Interaction analysis revealed that the prognostic impact of NIS was influenced by chemotherapy (P for interaction = 0.002). NIS was also strongly associated with severe malnutrition. Sensitivity analysis confirmed the robustness of these findings, even after excluding short-term mortalities within 180 days. Conclusions NIS are significant independent predictors of poor prognosis in gastric cancer patients, contributing to malnutrition and reduced survival. These findings highlight the importance of early symptom recognition and nutritional intervention to potentially improve outcomes for gastric cancer patients. Trial registration https://www.chictr.org.cn/showproj.html?proj=31813 , identifier ChiCTR1800020329.