TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

Enhancing urban blue-green landscape quality assessment through hybrid genetic algorithm-back propagation (GA-BP) neural network approach: a case study in Fucheng, China.

This study employs an artificial neural network optimization algorithm, enhanced with a Genetic Algorithm-Back Propagation (GA-BP) network, to assess the service quality of urban water bodies and green spaces, aiming to promote healthy urban environments. From an initial set of 95 variables, 29 key variables were selected, including 17 input variables, such as water and green space area, population size, and urbanization rate, six hidden layer neurons, such as patch number, patch density, and average patch size, and one output variable for the comprehensive value of blue-green landscape quality. The results indicate that the GA-BP network achieves an average relative error of 0.94772%, which is superior to the 1.5988% of the traditional BP network. Moreover, it boasts a prediction accuracy of 90% for the comprehensive value of landscape quality from 2015 to 2022, significantly outperforming the BP network's approximate 70% accuracy. This method enhances the accuracy of landscape quality assessment but also aids in identifying crucial factors influencing quality. It provides scientific and objective guidance for future urban landscape structure and layout, contributing to high-quality urban development and the creation of exemplary living areas.

Ammonia-dependent reducing power redistribution for purple phototrophic bacteria culture-based biohydrogen production.

The global energy crisis has intensified the search for sustainable and clean alternatives, with biohydrogen emerging as a promising solution to address environmental challenges. Leveraging photo fermentation (PF) process, purple phototrophic bacteria (PPB) can harness reducing power derived from organic substrates to facilitate hydrogen production. However, existing studies report much lower H2 yields than theoretical value when using acetate as carbon source and ammonia as nitrogen source, primarily attributed to the widely employed pulse-feeding mode which suffers from ammonia inhibition effect on nitrogenase. To address this issue, a continuous feeding mode was applied to avoid ammonia accumulation in this study. On the other hand, other pathways like carbon fixation and polyhydroxyalkanoate (PHA) formation could compete reducing power with H2 production. However, the reducing power allocation under continuous feeding mode is not yet clear. In this study, the reducing power allocation and hydrogen production performance were evaluated under various ammonia loading, using acetate as carbon source and infrared LED at around 50 W·m-2 as light source. The results show that (a) The absence of ammonia resulted in the best performance for hydrogen production, with 44 % of the reducing power distributed to H2 and the highest H2 volumetric productivity, while the allocation of reducing power to hydrogen production stopped when ammonia loading was above 7.6 mg NH4-N·L-1·d-1; (b) when PPB required to eliminate reducing power under ammonia limited conditions, PHA production was the preferred pathway followed by the hydrogen production pathway, but once PHA accumulation reached saturation, hydrogen generation pathway dominated; (c) under ammonia limited conditions, the TCA cycle was more activated rendering higher NADH (i.e. reducing power) production compared with that under ammonia sufficient conditions which was verified by metagenomics analysis, and all the hydrogen production, PHA accumulation and carbon fixation pathways were highly active to dissipate reducing power. This work provides the insight of reducing power distribution and PPB biohydrogen production variated by ammonia loading under continuous feeding mode.

Establishing an efficient membrane bioreactor for simultaneous pollutant removal and purple bacteria production under salinity stress.

Recovering resources from wastewater to alleviate the energy crisis has become the prevailing trend of technological development. Purple phototrophic bacteria (PPB), a group of fast-growing microbes, have been widely noticed for their potential in producing value-added products from waste streams. However, saline contents in these waste streams, such as food processing wastewater pose a big challenge, which not only restrain the pollutant removal efficiency, but also hinder the growth of functional microbes. To overcome this, a photo anaerobic membrane bioreactor cultivating PPB (PPB-MBR) was constructed and its performance upon long-term salinity stress was investigated. PPB-MBR achieved desirable pollutants removal performance with the average COD and NH4+ removal efficiency being 87% (±8%, n = 87) and 89% (±10%, n = 87), respectively during long-term exposure to salinity stress of 1-80 g NaCl L-1. PPB were predominant during the entire operation period of 87 days (60%-80%), obtaining maximum biomass yield of 0.67 g biomass g-1 CODremoved and protein productivity of 0.18 g L-1 d-1 at the salinity level of 20 g NaCl L-1 and 60 g NaCl L-1, respectively. The sum of value-added products in proportion to the biomass reached 58% at maximum at the salinity level of 60 g NaCl L-1 with protein, pigments and trehalose contributing to 44%, 8.7%, and 5%, respectively. Based on economic analysis, the most cost-saving scenario treating food processing wastewater was revealed at salinity level of around 20 g NaCl L-1. However, more optimization tools are needed to boost the production efficiency so that the profit from value-added products can outweigh the additional cost by excess salinity in the future implication.

Evaluation of dietary quality of patients with severe cerebrovascular disease by diet balance index-16.

OBJECTIVE: To assess the dietary quality of patients with severe cerebrovascular disease using Diet Balance Index-16 (DBI-16) and to provide scientific evidence for the establishment of targeted dietary intervention and related dietary nutritional education for patients. METHODS: The general information of 214 hospitalized patients with severe cerebrovascular disease, including gender and age etc., were investigated by a self-made questionnaire on health risk factors, and the dietary quality conditions of patients was evaluated by DBI-16 scoring method. RESULTS: The dietary quality of patients with severe cerebrovascular disease had low levels of imbalanced conditions, accompanied with low levels of inadequate intake and excessive intake. The degree of excessive intake in female patients was clearly less than that in male patients. The degree of inadequate intake and total scores in patients younger than 55 years old was lower than those in the other two groups. The intake of vegetables, fruits, milk and soybeans in most of patients did not reach the recommended nutrient intake and the animal product amount was insufficient. In addition, the intake of low quality food and condiments such as oil and salt were excessive in patients with severe cerebrovascular disease. Dietary pattern A was the main model. CONCLUSIONS: The overall diet structure of patients with severe cerebrovascular disease is not rational. It is recommended to appropriately balance the intake of grains and animal products, increase the intake of milk, soybeans, vegetables and fruits, and strictly control the amount of oil and salt.

The Wnt/ß-catenin signalling pathway in Haematological Neoplasms.

Leukaemia and lymphoma are common malignancies. The Wnt pathway is a complex network of proteins regulating cell proliferation and differentiation, as well as cancer development, and is divided into the Wnt/ß-catenin signalling pathway (the canonical Wnt signalling pathway) and the noncanonical Wnt signalling pathway. The Wnt/ß-catenin signalling pathway is highly conserved evolutionarily, and activation or inhibition of either of the pathways may lead to cancer development and progression. The aim of this review is to analyse the mechanisms of action of related molecules in the Wnt/ß-catenin pathway in haematologic malignancies and their feasibility as therapeutic targets.

Biliverdin Reductase A Protects Lens Epithelial Cells against Oxidative Damage and Cellular Senescence in Age-Related Cataract.

Age-related cataract (ARC) is the common cause of blindness globally. Reactive oxygen species (ROS), one of the greatest contributors to aging process, leads to oxidative damage and senescence of lens epithelial cells (LECs), which are involved in the pathogenesis of ARC. Biliverdin reductase A (BVRA) has ROS-scavenging ability by converting biliverdin (BV) into bilirubin (BR). However, little is known about the protective effect of BVRA against ARC. In the present study, we measured the expression level of BVRA and BR generation in human samples. Then, the antioxidative property of BVRA was compared between the young and senescent LECs upon stress condition. In addition, we evaluated the effect of BVRA on attenuating H2O2-induced premature senescence in LECs. The results showed that the mRNA expression level of BVRA and BR concentration were decreased in both LECs and lens cortex of age-related nuclear cataract. Using the RNA interference technique, we found that BVRA defends LECs against oxidative stress via (i) restoring mitochondrial dysfunction in a BR-dependent manner, (ii) inducing heme oxygenase-1 (HO-1) expression directly, and (iii) promoting phosphorylation of ERK1/2 and nuclear delivery of nuclear factor erythroid 2-related factor 2 (Nrf2). Intriguingly, the antioxidative effect of BVRA was diminished along with the reduced BR concentration and repressed nuclear translocation of BVRA and Nrf2 in senescent LECs, which would be resulted from the decreased BVRA activity and impaired nucleocytoplasmic trafficking. Eventually, we confirmed that BVRA accelerates the G1 phase transition and prevents against H2O2-induced premature senescence in LECs. In summary, BVRA protects LECs against oxidative stress and cellular senescence in ARC by converting BV into BR, inducing HO-1 expression, and activating the ERK/Nrf2 pathway. This trial is registered with ChiCTR2000036059.

The Above-Ground Part of Submerged Macrophytes Plays an Important Role in Ammonium Utilization.

As a paradoxical nutrient in water ecosystems, ammonium can promote plants growth under moderate concentration, but excess of it causes phytotoxic effects. Previous research has revealed that glutamate dehydrogenase in the above-ground part of submerged macrophytes plays an important role in ammonium detoxification. However, the strategies of ammonium utilization at the whole plant level of submerged macrophytes are still unclear and the role of the above-ground part in nutrient utilization has not been clearly elucidated in previous studies, hence, directly influencing the application of previous theory to practice. In the present research, we combined the methods of isotopic labeling and enzyme estimation to investigate strategies of ammonium utilization by the submerged macrophytes. The results showed that when [NH4 +-N] was 50 mg L-1, 15N taken up through the above-ground parts was 13.24 and 17.52 mg g-1 DW, while that of the below-ground parts was 4.24 and 8.54 mg g-1 DW in Potamogeton lucens and Myriophyllum spicatum, respectively. The ratios of 15N acropetal translocation to uptake were 25.75 and 35.69%, while those of basipetal translocation to uptake were 1.93 and 4.09% in P. lucens and M. spicatum, respectively. Our results indicated that the above-ground part was not only the main part for ammonium uptake, but also the major pool of exogenous ammonium. Besides, the dose-response curve of GDH (increased by 20.9 and 50.2% under 15 and 50 mg L-1 [NH4 +-N], respectively) exhibited by the above-ground parts of M. spicatum indicates that it is the main site for ammonium assimilation of the tolerant species. This study identifies the ammonium utilization strategy of submerged macrophytes and reveals the important role of the above-ground part in nutrient utilization providing new insight into the researches of nutrient utilization by plants and theoretical supports for water restoration by phytoremediation.

Regulating light, oxygen and volatile fatty acids to boost the productivity of purple bacteria biomass, protein and co-enzyme Q10.

Purple non­sulfur bacteria (PNSB) possess significant potential for bioresource recovery from wastewater. Effective operational tools are needed to boost productivity and direct the PNSB biomass towards abundant value-added substances (e.g., protein and co-enzyme Q10, CoQ10). This study aimed to investigate the impact of light, oxygen and volatile fatty acids (VFAs) on PNSB growth (i.e., Rhodobacter sphaeroides) and productivity of protein and CoQ10. Overall, the biomass yields and specific growth rates of PNSB were in the ranges of 0.57-1.08 g biomass g-1 CODremoved and 0.48-0.71 d-1, respectively. VFAs did not influence the biomass yield, yet acetate and VFA mixtures enhanced the specific growth rate with a factor of 1.2-1.5 compared to propionate and butyrate. The most PNSB biomass (1.08 g biomass g-1 CODremoved and 0.71 d-1) and the highest biomass quality (protein content of 609 mg g-1 dry cell weight (DCW) and CoQ10 content of 13.21 mg g-1 DCW) were obtained in the presence of VFA mixtures under natural light and microaerobic (low light alternated with darkness; dissolved oxygen (DO) between 0.5 and 1 mg L-1) conditions (vs. light anaerobic and dark aerobic cultivations). Further investigation on VFAs dynamics revealed that acetate was most rapidly consumed by PNSB in the individual VFA feeding (specific uptake rate of 0.76 g COD g-1 DCW d-1), while acetate as a co-substrate in the mixed VFAs feeding might accelerate the consumption of propionate and butyrate through providing additional cell metabolism precursor. Enzymes activities of succinate dehydrogenase and fructose-1,6-bisphosphatase as well as the concentration of photo pigments confirmed that light, oxygen and VFAs regulated the key enzymes in the energy metabolism and biomass synthesis to boost PNSB growth. These results provide a promising prospect for utilization of fermented waste stream for the harvest of PNSB biomass, protein and CoQ10.

Spectral bands of incandescent lamp leading to variable productivity of purple bacteria biomass and microbial protein: Full is better than segmented.

Purple non­sulfur bacteria (PNSB) are competent microorganisms capable of producing value-added products from waste streams. Light source is one of the most influential factors determining the efficiency of this process. Previous studies mostly focused on optimizing light intensity, while the impact of spectral bands on PNSB growth is still unknown. To fill the knowledge gap, this study investigated the responses of PNSB (i.e., Rhodobacter sphaeroides) growth, protein content and enzyme activity to various spectral bands of an incandescent lamp for the first time. It was found that the full spectrum of the incandescent lamp was propitious to cultivate PNSB than segmented spectral bands, as demonstrated by the maximum biomass yield of 1.05 g biomass g-1 CODremoved, specific growth rate of 0.53 d-1 and protein concentration of 0.48 g L-1. The production of biomass and protein under infrared (IR) spectral band were slightly lower than those under full spectrum, but 3.2 and 1.7 times higher than the average values (0.14 g L-1 and 0.07 g L-1) under visible spectral bands, respectively. The variation trends of enzymatic activities, such as fructose-1,6-bisphosphatase (FBP) and photopigments were consistent with that of PNSB biomass upon varying spectral bands, suggesting that the spectral bands might induce a variable PNSB biomass via affecting the Calvin cycle and photophosphorylation process. These results provide a new perspective that spectrum bands of light sources should be considered in the process optimization.

A mechanistic model for denitrifying anaerobic methane oxidation coupled to dissimilatory nitrate reduction to ammonium.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) is an important process linking nitrogen and carbon cycle. It is recently demonstrated that n-DAMO archaea are able to couple n-DAMO to dissimilatory nitrate reduction to ammonium (DNRA). In this work, a mathematical model is developed to describe DNRA by n-DAMO archaea for the first time. The anabolic and catabolic processes of n-DAMO archaea, n-DAMO bacteria and anaerobic ammonium oxidation (Anammox) bacteria are involved. The different impacts of exogenous and endogenous nitrite on DNRA and n-DAMO microbes are considered. The developed model is calibrated and validated using experimental data collected from a sequencing batch reactor (SBR) and a counter-diffusion membrane biofilm bioreactor (MBfR). The model outputs fit well with the profiles of nitrogen (N) dynamics and biomass changes in both reactors, demonstrating its good predictive ability. The developed model is further used to simulate the counter-diffusion MBfR incorporating n-DAMO and Anammox process to treat sidestream wastewater. The simulated distribution profiles of N removal/production rates by different microbes along biofilm depth reveal that DNRA by n-DAMO archaea plays an important role in N transformation of the integrated n-DAMO and Anammox process. It is further suggested that the counter-diffusion MBfR under the investigated conditions should be operated at proper hydraulic retention times (HRTs) (i.e. 6h and 8h) with exogenous NO2- in the range of 0-10 mg N/L or at HRTs >3h with the absence of exogenous NO2- in order to achieve dischargeable effluent.

An AI-based auxiliary empirical antibiotic therapy model for children with bacterial pneumonia using low-dose chest CT images.

PURPOSE: To construct an auxiliary empirical antibiotic therapy (EAT) multi-class classification model for children with bacterial pneumonia using radiomics features based on artificial intelligence and low-dose chest CT images. MATERIALS AND METHODS: Data were retrospectively collected from children with pathogen-confirmed bacterial pneumonia including Gram-positive bacterial pneumonia (122/389, 31%), Gram-negative bacterial pneumonia (159/389, 41%) and atypical bacterial pneumonia (108/389, 28%) from January 1 to June 30, 2019. Nine machine-learning models were separately evaluated based on radiomics features extracted from CT images; three optimal submodels were constructed and integrated to form a multi-class classification model. RESULTS: We selected five features to develop three radiomics submodels: a Gram-positive model, a Gram-negative model and an atypical model. The comprehensive radiomics model using support vector machine method yielded an average area under the curve (AUC) of 0.75 [95% confidence interval (CI), 0.65-0.83] and accuracy (ACC) of 0.58 [sensitivity (SEN), 0.57; specificity (SPE), 0.78] in the training set, and an average AUC of 0.73 (95% CI 0.61-0.79) and ACC of 0.54 (SEN, 0.52; SPE, 0.75) in the test set. CONCLUSION: This auxiliary EAT radiomics multi-class classification model was deserved to be researched in differential diagnosing bacterial pneumonias in children.

Identification of PSMD7 as a prognostic factor correlated with immune infiltration in head and neck squamous cell carcinoma.

BACKGROUND: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Proteasome 26S subunit, non-ATPase 7 (PSMD7) is an ATP-independent component of the 19S regulatory subunit. The prognostic value of PSMD7 and the association with immune infiltration in HNSCC remains unclear. METHODS: The Sangerbox, Oncomine, UALCAN and Human Protein Atlas (HPA) databases were used to examine PSMD7 expression profiles in HNSCC. The CVCDAP was used to analysis the association of PSMD7 with the prognosis of patients with HNSCC. The mechanism was investigated with gene set enrichment analysis (GSEA). The association between expression of PSMD7 and immune infiltration in HNSCC was investigated using the Tumor Immune Estimation Resource (TIMER), TISIDB database and CIBERSORT algorithm. RESULTS: PSMD7 expression was significantly up-regulated in HNSCC compared with relative normal tissues. In addition, up-regulated PSMD7 expression was associated with various clinicopathological parameters. High expression of PSMD7 suggested inferior survival of HNSCC patients. GSEA and CERES score indicated that PSMD7 was closely correlated with tumor-related signaling pathways and cell survival. Functional analyses revealed that PSMD7 was positively correlated with various infiltration levels. Moreover, PSMD7 influenced the prognosis of HNSCC patients partially via immune infiltration. CONCLUSION: Our findings suggest that PSMD7 is associated poor prognosis in patients with HNSCC and plays an important role in tumor-related immune infiltration.

Consumer health information needs in China - a case study of depression based on a Social Q&A community.

BACKGROUND: The social Q&A community quickly becomes a popular platform for consumers to find health information because of its convenience and interactivity. METHODS: Based on the 10,861 depression questions collected in the Zhihu, the largest Q&A platform in China, we divided the healthy information needs description into nine categories with Latent Dirichlet Allocation (LDA). We also divided the healthy information needs type into Physiological, affective and cognitive needs based on the Wilson model. RESULTS: The results show that the largest categories are depression symptom and social activities while the less concerned health information is prevention and medical insurance. More attention is paid to cognitive needs. We also find there is no strong correlation between attention and needs type. CONCLUSIONS: The purpose of this paper is to refine the consumer health information needs types to better understand the consumer health information characteristic in China.

Black carbon and mercury in the surface sediments of Selin Co, central Tibetan Plateau: Covariation with total carbon.

Tibetan Plateau (TP) is an important geographical region for investigating the long-range transport of pollutants as limited emission sources exist in this region. In this study, based on analysis of 61 surface samples, we report the spatial distribution and concentrations of BC, Hg, total organic carbon (TOC) and inorganic carbon (IC) in surface sediments of Selin Co, the largest lake in central Tibet. The mean BC and Hg concentrations were 0.62 ± 0.34 mg/g and 32.03 ± 9.88 ng/g (range: 0.03-1.47 mg/g and 13.83-51.81 ng/g respectively), which were lower than the values from other lakes in the Himalayan-Tibetan Plateau (HTP). BC and Hg exhibited similar spatial distribution in the surface sediments. Similarly, the mean TOC and IC were 2.19 ± 1.46% and 3.13 ± 1.07% (range: 0.0007-7.78% and 0.30-5.30% respectively). BC/TOC ratio, as well as char/soot ratio, suggests biomass burning as a major source of BC in the sediments via the influence of long-range transport. The positive correlation between the concentrations of BC and Hg suggests similar emission sources or transport pathway. Concentrations of BC and Hg were higher in fine grain particles (size <~50 µm) which were capable of transport and deposit in the deeper part of the lake, as suggested by a significant relationship between water depth and particle size. This study elucidates the extent of pollution in very recent ages and also could serve as the basis for paleo-environmental studies in future.

Investigation into Information Release of Chinese Government and Departments on COVID-19.

Information release is an important way for governments to deal with public health emergencies, and plays an irreplaceable role in promoting epidemic prevention and control, enhancing public awareness of the epidemic situation and mobilizing social resources. Focusing on the coronavirus disease 2019 (COVID-19) epidemic in China, this investigation chose 133 information release accounts of the Chinese government and relevant departments at the national, provincial, and municipal levels, including Ministries of the State Council, Departments of Hubei Province Government, and Bureaus of Wuhan Government, covering their portals, apps, Weibos, and WeChats. Then, the characteristics such as scale, agility, frequency, originality, and impact of different levels, departments, and channels of the information releases by the Chinese government on the COVID-19 epidemic were analyzed. Finally, the overall situation was concluded by radar map analysis. It was found that the information release on the COVID-19 epidemic was coordinated effectively at different levels, departments, and channels, as evidenced by the complementarity between channels, the synergy between the national and local governments, and the coordination between departments, which guaranteed the rapid success of the epidemic prevention and control process in China. This investigation could be a reference for epidemic prevention and control for governments and international organizations, such as the World Health Organization (WHO), during public health emergencies, e.g. the COVID-19 pandemic.

Association between folate intake and risk of head and neck squamous cell carcinoma: An overall and dose-response PRISMA meta-analysis.

The results of published studies about the relationships between folate intake and risk of head and neck squamous cell carcinoma (HNSCC) remained inconsistent. Hence, a comprehensive and dose-response meta-analysis was performed to clarify the association between folate intake and HNSCC risk.The electric searches of Pubmed, Medline, and EMBASE databases were performed to identify the studies examining the relationship between folate intake and HNSCC risk on April 5, 2017. According to the inclusion criteria, finally 9 studies were included in this meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Dose-response analysis was conducted to quantitate the relationship between dietary folate intake and HNSCC risk.The pooled OR for assessing the risk of HNSCC and folate intake in the highest level versus lowest level was 0.505 (95% CI 0.387-0.623). The linearity model of dose-response analysis indicated that with increased 100 µg/d folate intake, the risk of HNSCC decreased 4.3% degree (OR 0.957, 95% CI 0.935-0.980).These results indicate that folate is a protective nutrient against HNSCC carcinogenesis.