Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial.

Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with <20 sites (HR 0.69, 95% CI 0.46-1.03). Patients with a complete resection had the most favorable outcome, with a median OS of 73.0 months. Twenty-four of 182 (13.2%) patients remained relapse free and alive >60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .

Analysis of Imaging and Pathologic Features in Eosinophilic Solid and Cystic Renal Cell Carcinoma.

OBJECTIVE: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is rare and difficult to diagnose. Therefore, we aim to investigate the imaging and pathologic features of ESC-RCC. METHODS: Fifteen cases of ESC-RCC with pathologically confirmed diagnoses were retrospectively collected: CT was performed in 15 cases and MRI in 9 cases. RESULTS: In these patients (6 males and 9 females) (age: mean, 53.3 ± 14.7 years; range, 27-72 years), all tumors were unilateral, renal, and solitary with no clinical symptoms and were classified into-type 1: cystic-solid component, with equal cystic and solid components, was the most common (8/15, 53.3%); type 2: predominantly cystic with a small solid component (4/15, 26.7%); and type 3: predominantly solid (3/15, 20%). The solid component showed equal/slightly higher density on the CT-plain-scan, equal/slightly high signal on the T1-weighted image (T1WI), and low signal on the T2-weighted image (T2WI). Ten cases showed progressive enhancement, while 5 showed a fast-wash-in and fast-wash-out enhancement. One patient experienced hemorrhage, while the others showed no signs of hemorrhage, necrosis, fat, or calcification. Pathologically, the tumor showed cystic solidity, with eosinophilic cytoplasm and granular basophilic-colored spots with focal or diffuse expression of CK20. Ten patients had componential nephrectomy and 5 had radical nephrectomy. No recurrence or metastasis was noted in any case at the follow-up (8-49 months). CONCLUSION: This study describes the imaging and pathologic features of a rare type of renal cancer and proposes 3 imaging types to enhance physicians' diagnosis of this disease and guide clinical diagnosis and treatment.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

A multifactor hybrid model for carbon price interval prediction based on decomposition-integration framework.

Carbon price is a pivotal element in the carbon trading sector. Accurate estimation of carbon price can offer precise guidance for the carbon market participants. This study introduces a novel prediction model encompassing both point and interval prediction for the carbon price. Firstly, to distill the volatility traits inherent in carbon price, the successive variational mode decomposition is utilized to adaptively decompose the carbon price into regular sequences. Secondly, to obtain the optimal input variables, the partial autocorrelation function and random forest are employed to filter the influencing factors and historical carbon price. Then, to avoid single model constraint, a combination model of categorical boosting and kernel extreme learning machine optimized by the sparrow search algorithm is employed for the point prediction, and the shapley additive explanation is employed to elucidate the model prediction process. Finally, to provide more efficient information, the adaptive bandwidth kernel density estimation is applied to the interval prediction. The data from Hubei carbon market is adopted as a case study, and the results indicate that the mean absolute error, mean absolute percentage error, root mean square error and R2 of the proposed model are 0.1022, 0.0022, 0.1262 and 0.9921, respectively. The historical carbon price, Brent crude oil futures settlement price and European Union allowance futures carbon price have a positive impact on carbon price, and Hushen 300 has a negative impact on carbon price. Compared with the constant kernel density estimation, the proposed model achieves higher interval coverage probability and lower interval width. Thus, the application of the hybrid model can promote the operational efficiency of the carbon market and facilitate the implementation of carbon emission reduction policies.

Mrakia polaris sp. nov. and Mrakia amundsenii sp. nov. (Mrakiaceae, Cystofilobasidiales), two novel psychrophilic yeast species isolated from Arctic habitats.

Four yeast strains belonging to the basidiomycetous yeast genus Mrakia were isolated from diverse habitats in the Ny-Ålesund region (Svalbard, High Arctic): two from vascular plants, one from seawater and one from freshwater. Phylogenetic analysis, based on the ITS region and the D1/D2 domain of the 28S rRNA gene, identified these four strains as representing two novel species within the genus Mrakia. The names Mrakia polaris sp. nov. (MycoBank number: MB 852063) and Mrakia amundsenii sp. nov. (MycoBank number: MB 852064) are proposed. These two new species show distinct psychrophilic adaptations, as they exhibit optimal growth at temperatures between 10 and 15°C, while being unable to grow at 25°C. The holotype of M. polaris sp. nov. is CPCC 300345T, and the holotype of M. amundsenii sp. nov. is CPCC 300572T.

Clinical characteristics of liver transplant recipients with COVID-19 and analysis of risk factors for the severe disease.

INTRODUCTION: Liver transplant (LT) recipients were at a high risk of infection during the coronavirus disease 2019 (COVID-19) pandemic. Our purpose was to compare the clinical characteristics of severe and non-severe groups of LT recipients with COVID-19, and to analyze their risk factors for severe disease. METHODOLOGY: 79 LT recipients with COVID-19 were divided into a non-severe group (n = 60) and a severe group (n = 19), and differences in clinical characteristics, laboratory tests, and chest computed tomography (CT) performance were analyzed. Logistic regression was used to identify risk factors with severe COVID-19. Receiver operating characteristic (ROC) curves were plotted and the area under curve (AUC) values were calculated to assess the predictive value for severe COVID-19. RESULTS: Age was statistically different (p < 0.001) between the two groups. The difference in neutrophil-to-lymphocyte ratio (NLR), serum creatinine (Scr), D-dimer, urea, C-reactive protein (CRP), lactate dehydrogenase (LDH), and the number of lung segments involved in inflammation between the two groups were statistically significant (p < 0.05). The results revealed that age (OR = 1.255, 95% CI 1.079-1.460), NLR (OR = 1.172, 95% CI 1.019-1.348), and Scr (OR = 1.041, 95% CI 1.016-1.066) were independent risk factors for severe COVID-19. The ROC results showed that high values for age, NLR and Scr predicted severe COVID-19, with AUC values of 0.775, 0.841 and 0.820, respectively, and 0.925 for the three factors combined. CONCLUSIONS: Advanced age, and elevated NLR and Scr are independent risk factors for severe COVID-19 in LT recipients.

The relationship between childhood adversity and sleep quality among rural older adults in China: the mediating role of anxiety and negative coping.

BACKGROUND: Studies have revealed the effects of childhood adversity, anxiety, and negative coping on sleep quality in older adults, but few studies have focused on the association between childhood adversity and sleep quality in rural older adults and the potential mechanisms of this influence. In this study, we aim to evaluate sleep quality in rural older adults, analyze the impact of adverse early experiences on their sleep quality, and explore whether anxiety and negative coping mediate this relationship. METHODS: Data were derived from a large cross-sectional study conducted in Deyang City, China, which recruited 6,318 people aged 65 years and older. After excluding non-agricultural household registration and lack of key information, a total of 3,873 rural older adults were included in the analysis. Structural equation modelling (SEM) was used to analyze the relationship between childhood adversity and sleep quality, and the mediating role of anxiety and negative coping. RESULTS: Approximately 48.15% of rural older adults had poor sleep quality, and older adults who were women, less educated, widowed, or living alone or had chronic illnesses had poorer sleep quality. Through structural equation model fitting, the total effect value of childhood adversity on sleep quality was 0.208 (95% CI: 0.146, 0.270), with a direct effect value of 0.066 (95% CI: 0.006, 0.130), accounting for 31.73% of the total effect; the total indirect effect value was 0.142 (95% CI: 0.119, 0.170), accounting for 68.27% of the total effect. The mediating effects of childhood adversity on sleep quality through anxiety and negative coping were significant, with effect values of 0.096 (95% CI: 0.078, 0.119) and 0.024 (95% CI: 0.014, 0.037), respectively. The chain mediating effect of anxiety and negative coping between childhood adversity and sleep quality was also significant, with an effect value of 0.022 (95% CI: 0.017, 0.028). CONCLUSIONS: Anxiety and negative coping were important mediating factors for rural older adult's childhood adversity and sleep quality. This suggests that managing anxiety and negative coping in older adults may mitigate the negative effects of childhood adversity on sleep quality.

Engineering Spin Polarization of the Surface-Adsorbed Fe Atom by Intercalating a Transition Metal Atom into the MoS2 Bilayer for Enhanced Nitrogen Reduction.

The precise control of spin states in transition metal (TM)-based single-atom catalysts (SACs) is crucial for advancing the functionality of electrocatalysts, yet it presents significant scientific challenges. Using density functional theory (DFT) calculations, we propose a novel mechanism to precisely modulate the spin state of the surface-adsorbed Fe atom on the MoS2 bilayer. This is achieved by strategically intercalating a TM atom into the interlayer space of the MoS2 bilayer. Our results show that these strategically intercalated TM atoms can induce a substantial interfacial charge polarization, thereby effectively controlling the charge transfer and spin polarization on the surface Fe site. In particular, by varying the identity of the intercalated TM atoms and their vacancy filling site, a continuous modulation of the spin states of the surface Fe site from low to medium to high can be achieved, which can be accurately described using descriptors composed of readily accessible intrinsic properties of materials. Using the electrochemical dinitrogen reduction reaction (eNRR) as a prototypical reaction, we discovered a universal volcano-like relation between the tuned spin and the catalytic activity of Fe-based SACs. This finding contrasts with the linear scaling relationships commonly seen in traditional studies and offers a robust new approach to modulating the activity of SACs through interfacial engineering.

Sphingomonas lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic cyanobacterium.

An alpha-proteobacterial strain JXJ CY 53 T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53 T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C18:1ω7c and C16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761 T and Sphingomonas hankookensis KCTC 22579 T, respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53 T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53 T = KCTC 72813 T = CGMCC 1.17657 T). JXJ CY 53 T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53 T dissolved organic carbon for growth, and control the growth of JXJ CY 53 T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs).

Co-occurrence patterns of gut microbiome, antibiotic resistome and the perturbation of dietary uptake in captive giant pandas.

The microbiome is a key source of antibiotic resistance genes (ARGs), significantly influenced by diet, which highlights the interconnectedness between diet, gut microbiome, and ARGs. Currently, our understanding is limited on the co-occurrence among gut microbiome, antibiotic resistome in the captive giant panda and the perturbation of dietary uptake, especially for the composition and forms in dietary nutrition. Here, a qPCR array with 384 primer sets and 16 S rRNA gene amplicon sequencing were used to characterize the antibiotic resistome and microbiomes in panda feces, dietary bamboo, and soil around the habitat. Diet nutrients containing organic and mineral substances in soluble and insoluble forms were also quantified. Organic and mineral components in water-unextractable fractions were 7.5 to 139 and 637 to 8695 times higher than those in water-extractable portions in bamboo and feces, respectively, while the latter contributed more to the variation (67.5 %) of gut microbiota. Streptococcus, Prevotellaceae, and Bacteroides were the dominant genera in giant pandas. The ARG patterns in panda guts showed higher diversity in old individuals but higher abundance in young ones, driven directly by the bacterial community change and mobile genetic element mediation and indirectly by dietary intervention. Our results suggest that dietary nutrition mainly accounts for the shift of gut microbiota, while bacterial community and mobile genetic elements influenced the variation of gut antibiotic resistome.

Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Modulation of growth, microcystin production, and algal-bacterial interactions of the bloom-forming algae Microcystis aeruginosa by a novel bacterium recovered from its phycosphere.

Harmful algal blooms (HABs) in natural waters are of escalating global concern due to their detrimental impact on environmental health. Emerging evidence indicates that algae-bacteria symbionts can affect HAB features, though much about this interplay remains largely unexplored. The current study isolated a new species of Mucilaginibacter (type strain JXJ CY 39T) from culture biomass of the bloom-causing Microcystis aeruginosa FACHB-905 (Maf) from Lake Dianchi, China. Strain JXJ CY 39T was an aerobic, Gram-stain-negative rod bacterium that grew at 5-38°C, pH 4.0-11.0, and 0-3.0% NaCl. Taxonomic evaluation proposed a new species, with Mucilaginibacter lacusdianchii sp. nov., as the species epithet. Experimental results revealed that strain JXJ CY 39T spurred the growth of Maf by supplying soluble phosphorus and nitrogen during cultivation, despite the unavailability of soluble phosphorus and nitrogen. Additionally, by producing the plant hormone indole-3-acetate, strain JXJ CY 39T possibly impacted Maf's functionality. Results from co-culture experiments with other strains from Maf biomass showed possible effects of strain JXJ CY 39T on the relationship between Maf and other cohabiting bacteria, as well as microcystin toxin production characteristics. Although Maf could foster the growth of strain JXJ CY 39T by supplying organic carbon, the strain's growth could be regulated via specific chemical compounds based on antibiotic assays. Community composition analysis disclosed that this Mucilaginibacter strain positively affected Maf's growth and modified densities and types of bacteria linked to Maf. Overall, these results suggest that the interactions between important HAB-causing organisms and their attached bacteria are complex, dynamic, and may influence the growth characteristics of algae.

Long-term PM1 exposure and hypertension hospitalization: A causal inference study on a large community-based cohort in South China.

Limited evidence exists on the effect of submicronic particulate matter (PM1) on hypertension hospitalization. Evidence based on causal inference and large cohorts is even more scarce. In 2015, 36,271 participants were enrolled in South China and followed up through 2020. Each participant was assigned single-year, lag0-1, and lag0-2 moving average concentration of PM1 and fine inhalable particulate matter (PM2.5) simulated based on satellite data at a 1-km resolution. We used an inverse probability weighting approach to balance confounders and utilized a marginal structural Cox model to evaluate the underlying causal links between PM1 exposure and hypertension hospitalization, with PM2.5-hypertension association for comparison. Several sensitivity studies and the analyses of effect modification were also conducted. We found that a higher hospitalization risk from both overall (HR: 1.13, 95% CI: 1.05-1.22) and essential hypertension (HR: 1.15, 95% CI: 1.06-1.25) was linked to each 1 µg/m3 increase in the yearly average PM1 concentration. At lag0-1 and lag0-2, we observed a 17%-21% higher risk of hypertension associated with PM1. The effect of PM1 was 6%-11% higher compared with PM2.5. Linear concentration-exposure associations between PM1 exposure and hypertension were identified, without safety thresholds. Women and participants that engaged in physical exercise exhibited higher susceptibility, with 4%-22% greater risk than their counterparts. This large cohort study identified a detrimental relationship between chronic PM1 exposure and hypertension hospitalization, which was more pronounced compared with PM2.5 and among certain groups.

Investigation of the migration of natural organic matter-iron-antimony nano-colloids in acid mine drainage.

Colloids can potentially affect the efficacy of traditional acid mine drainage (AMD) treatment methods such as precipitation and filtration. However, it is unclear how colloids affect antimony (Sb) migration in AMD, especially when natural organic matter (NOM) is present. To conduct an in-depth investigation on the formation and migration behavior of NOM, iron (Fe), Sb and NOM-Fe-Sb colloids in AMD, experiments were performed under simulated AMD conditions. The results demonstrate significant variations in the formation of NOM-Fe-Sb colloids (1-3-450 nm) as the molar ratio of carbon to iron (C/Fe) increases within acidic conditions (pH = 3). Increasing the C/Fe molar ratio from 0.1 to 1.2 resulted in a decrease in colloid formation but an increase in particulate fraction. The distribution of colloidal Sb, Sb(III), and Fe(III) within the NOM-Fe-Sb colloids decreased from 68 % to 55 %, 72 % to 57 %, and 68 % to 55 %, respectively. Their distribution in the particulate fraction increased from 28 % to 42 %, 21 % to 34 %, and 8 % to 27 %. XRD, FTIR, and SEM-EDS analyses demonstrated that NOM facilitates the formation and crystallization of Fe3O4 and FeSbO4 crystalline phases. The formation of the colloids depended on pH. Our results indicate that NOM-Fe-Sb colloids can form when the pH ≤ 4, and the proportion of colloidal Sb fraction within the NOM-Fe-Sb colloids increased from 9 % to a maximum of 73 %. Column experiments show that the concentration of NOM-Fe-Sb colloids reaches its peak and remains stable at approximately 3.5 pore volumes (PVs), facilitating the migration of Sb in the porous media. At pH ≥ 5, stable NOM-Fe-Sb colloids do not form, and the proportion of colloidal Sb fraction decreases from 7 % to 0 %. This implies that as pH increases, the electrostatic repulsion between colloidal particles weakens, resulting in a reduction in the colloidal fraction and an increase in the particulate fraction. At higher pH values (pH ≥ 5), the repulsive forces between colloidal particles nearly disappear, promoting particle aggregation. The findings of this study provide important scientific evidence for understanding the migration behavior of NOM-Fe-Sb colloids in AMD. As the pH gradually shifts from acidic to near-neutral pH during the remediation process of AMD, these results could be applied to develop new strategies for this purpose.

Aucubin alleviates doxorubicin-induced cardiotoxicity through crosstalk between NRF2 and HIPK2 mediating autophagy and apoptosis.

BACKGROUND: Doxorubicin (DOX) is widely used for the treatment of a variety of cancers. However, its clinical application is limited by dose-dependent cardiotoxicity. Recent findings demonstrated that autophagy inhibition and apoptosis of cardiomyocytes induced by oxidative stress dominate the pathophysiology of DOX-induced cardiotoxicity (DIC), however, there are no potential molecules targeting on these. PURPOSE: This study aimed to explore whether aucubin (AU) acting on inimitable crosstalk between NRF2 and HIPK2 mediated the autophagy, oxidative stress, and apoptosis in DIC, and provide a new and alternative strategy for the treatment of DIC. METHODS AND RESULTS: We first demonstrated the protection of AU on cardiac structure and function in DIC mice manifested by increased EF and FS values, decreased serum CK-MB and LDH contents and well-aligned cardiac tissue in HE staining. Furthermore, AU alleviated DOX-induced myocardial oxidative stress, mitochondrial damage, apoptosis, and autophagy flux dysregulation in mice, as measured by decreased ROS, 8-OHdG, and TUNEL-positive cells in myocardial tissue, increased SOD and decreased MDA in serum, aligned mitochondria with reduced vacuoles, and increased autophagosomes. In vitro, AU alleviated DOX-induced oxidative stress, autophagy inhibition, and apoptosis by promoting NRF2 and HIPK2 expression. We also identified crosstalk between NRF2 and HIPK2 in DIC as documented by overexpression of NRF2 or HIPK2 reversed cellular oxidative stress, autophagy blocking, and apoptosis aggravated by HIPK2 or NRF2 siRNA, respectively. Simultaneously, AU promoted the expression and nuclear localization of NRF2 protein, which was reversed by HIPK2 siRNA, and AU raised the expression of HIPK2 protein as well, which was reversed by NRF2 siRNA. Crucially, AU did not affect the antitumor activity of DOX against MCF-7 and HepG2 cells, which made up for the shortcomings of previous anti-DIC drugs. CONCLUSION: These collective results innovatively documented that AU regulated the unique crosstalk between NRF2 and HIPK2 to coordinate oxidative stress, autophagy, and apoptosis against DIC without compromising the anti-tumor effect of DOX in vitro.

Concurrent enhancement of biomass production and phycocyanin content in salt-stressed Arthrospira platensis: A glycine betaine- supplementation approach.

In industrial-scale cultivation of microalgae, salinity stress often stimulates high-value metabolites production but decreases biomass yield. In this research, we present an extraordinary response of Arthrospira platensis to salinity stress. Specifically, we observed a significant increase in both biomass production (2.58 g L-1) and phycocyanin (PC) content (22.31%), which were enhanced by 1.26-fold and 2.62-fold, respectively, compared to the control, upon exposure to exogenous glycine betaine (GB). The biochemical analysis reveals a significant enhancement in carbonic anhydrase activity and chlorophyll a level, concurrent with reductions in carbohydrate content and reactive oxygen species (ROS) levels. Further, transcriptomic profiling indicates a downregulation of genes associated with the tricarboxylic acid (TCA) cycle and an upregulation of genes linked to nitrogen assimilation, hinting at a rebalanced carbon/nitrogen metabolism favoring PC accumulation. This work thus presents a promising strategy for simultaneous enhancement of biomass production and PC content in A. platensis and expands our understanding of PC biosynthesis and salinity stress responses in A. platensis.

Value of diffusion kurtosis MR imaging and conventional diffusion weighed imaging for evaluating response to first-line chemotherapy in unresectable pancreatic cancer.

OBJECTIVE: To investigate the diagnostic value of diffusion kurtosis magnetic resonance imaging (DKI) and conventional diffusion-weighted imaging (DWI) for evaluating the response to first-line chemotherapy in unresectable pancreatic cancer. MATERIALS AND METHODS: We retrospectively analyzed 21 patients with clinically and pathologically confirmed unresected pancreatic cancer who received palliative chemotherapy. Three-tesla MRI examinations containing DWI sequences with b values of 0, 100, 700, 1400, and 2100 s/mm2 were performed before and after chemotherapy. Parameters included the apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), and mean diffusional kurtosis (MK). The performances of the DWI and DKI parameters in distinguishing the response to chemotherapy were evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Overall survival (OS) was calculated from the date of first treatment to the date of death or the latest follow-up date. RESULTS: The ADCchange and MDchange were significantly higher in the responding group (PR group) than in the nonresponding group (non-PR group) (ADCchange: 0.21 ± 0.05 vs. 0.11 ± 0.09, P = 0.02; MDchange: 0.37 ± 0.24 vs. 0.10 ± 0.12, P = 0.002). No statistical significance was shown when comparing ADCpre, ADCpost, MKpre, MKpost, MKchange, MDpre, and MDpost between the PR and non-PR groups. The ROC curve analysis indicated that MDchange (AUC = 0.898, cutoff value = 0.7143) performed better than ADCchange (AUC = 0.806, cutoff value = 0.1369) in predicting the response to chemotherapy. CONCLUSION: The ADCchange and MDchange demonstrated strong potential for evaluating the response to chemotherapy in unresectable pancreatic cancer. The MDchange showed higher specificity in the classification of PR and non-PR than the ADCchange. Other parameters, including ADCpre, ADCpost, MKpre, MKpost, MKchange, MDpre, and MDpost, are not suitable for response evaluation. The combined model SUMchange demonstrated superior performance compared to the individual DWI and DKI models. Further experiments are needed to evaluate the potential of DWI and DKI parameters in predicting the prognosis of patients with unresectable pancreatic cancer.

Sleep duration and mortality in patients with chronic noncommunicable disease: a population-based cohort study.

BACKGROUND: Inadequate sleep behaviors may confer a higher risk of premature death, however, evidence in patients with chronic noncommunicable disease (NCD) is scarce. To investigate the relationship between sleep duration and mortality from all-cause and heart diseases in NCD patients from a prospective cohort. METHODS: Totally, 14,171 participants with at least one NCD, including 8275 with hypertension, 7547 with high cholesterol, 4065 with diabetes, and 5815 with chronic renal failure were enrolled from the National Health and Nutrition Examination Survey during 2005-2014. Cox proportional hazard models were performed to estimate the hazard ratio (HR) for sleep duration and mortality after adjusting for potential confounding factors. RESULTS: After a median follow-up of 9 years, 2514 all-cause deaths were identified. Compared with sleeping 7-8 h/day, sleeping over 8 h/day was significantly associated with a higher risk of all-cause mortality, where the multivariable-HRs were 1.29 (1.11, 1.50) for hypertension, 1.23 (1.01, 1.51) for high cholesterol, 1.44 (1.13, 1.82) for diabetes, and 1.36 (1.10, 1.68) for chronic renal failure. Similar patterns were observed for heart disease mortality. A nonlinear association was detected between sleep duration and mortality in patients with NCD. Age modified the association in patients with hypertension (P-interaction: 0.036). Trouble sleeping modified the association in patients with diabetes (P-interaction: 0.042). CONCLUSIONS: Long sleep duration was associated with higher risks of all-cause and heart disease mortality in patients with chronic NCD. Our findings highlight that improving sleep behaviors may decrease the risk of premature deaths and help to NCD tertiary prevention.

Short-term effects of air pollutants on hospital admissions for asthma among older adults: a multi-city time series study in Southwest, China.

Background: This study aimed to explore the relationship between air pollution and hospital admissions for asthma in older adults, and to further assess the health and economic burden of asthma admissions attributable to air pollution. Methods: We collected information on asthma cases in people over 65 years of age from nine cities in Sichuan province, as well as air pollution and meteorological data. The relationship between short-term air pollutant exposure and daily asthma hospitalizations was analyzed using the generalized additive model (GAM), and stratified by gender, age, and season. In addition, we assessed the economic burden of hospitalization for air pollution-related asthma in older adults using the cost of disease approach. Results: The single pollutant model showed that every 1 mg/m3 increase in CO was linked with an increase in daily hospitalizations for older adults with asthma, with relative risk values of 1.327 (95% CI: 1.116-1.577) at lag7. Each 10 µg/m3 increase in NO2, O3, PM10, PM2.5 and SO2, on asthma hospitalization, with relative risk values of 1.044 (95% CI: 1.011-1.078), 1.018 (95% CI: 1.002-1.034), 1.013 (95% CI: 1.004-1.022), 1.015 (95% CI: 1.003-1.028) and 1.13 (95% CI: 1.041-1.227), respectively. Stratified analysis shows that stronger associations between air pollution and asthma HAs among older adult in females, those aged 65-69 years, and in the warm season, although all of the differences between subgroups did not reach statistical significance. During the study period, the number of asthma hospitalizations attributable to PM2.5, PM10, and NO2 pollution was 764, 581 and 95, respectively, which resulted in a total economic cost of 6.222 million CNY, 4.73 million CNY and 0.776 million CNY, respectively. Conclusion: This study suggests that short-term exposure to air pollutants is positively associated with an increase in numbers of asthma of people over 65 years of age in Sichuan province, and short-term exposure to excessive PM and NO2 brings health and economic burden to individuals and society.

Potential causal links and mediation pathway between urban greenness and lung cancer mortality: Result from a large cohort (2009 to 2020).

Urban greenness, as a vital component of the urban environment, plays a critical role in mitigating the adverse effects of rapid urbanization and supporting urban sustainability. However, the causal links between urban greenness and lung cancer mortality and its potential causal pathway remain poorly understood. Based on a prospective community-based cohort with 581,785 adult participants in southern China, we applied a doubly robust Cox proportional hazard model to estimate the causal associations between urban greenness exposure and lung cancer mortality. A general multiple mediation analysis method was utilized to further assess the potential mediating roles of various factors including particulate matter (PM1, PM2.5-1, and PM10-2.5), temperature, physical activity, and body mass index (BMI). We observed that each interquartile range (IQR: 0.06) increment in greenness exposure was inversely associated with lung cancer mortality, with a hazard ratio (HR) of 0.89 (95 % CI: 0.83, 0.96). The relationship between greenness and lung cancer mortality might be partially mediated by particulate matter, temperature, and physical activity, yielding a total indirect effect of 0.826 (95 % CI: 0.769, 0.887) for each IQR increase in greenness exposure. Notably, the protective effect of greenness against lung cancer mortality could be achieved primarily by reducing the particulate matter concentration.