Potential risk assessment and occurrence characteristic of heavy metals based on artificial neural network model along the Yangtze River Estuary, China.

Pollution from heavy metals in estuaries poses potential risks to the aquatic environment and public health. The complexity of the estuarine water environment limits the accurate understanding of its pollution prediction. Field observations were conducted at seven sampling sites along the Yangtze River Estuary (YRE) during summer, autumn, and winter 2021 to analyze the concentrations of seven heavy metals (As, Cd, Cr, Pb, Cu, Ni, Zn) in water and surface sediments. The order of heavy metal concentrations in water samples from highest to lowest was Zn > As > Cu > Ni > Cr > Pb > Cd, while that in surface sediments samples was Zn > Cr > As > Ni > Pb > Cu > Cd. Human health risk assessment of the heavy metals in water samples indicated a chronic and carcinogenic risk associated with As. The risks of heavy metals in surface sediments were evaluated using the geo-accumulation index (Igeo) and potential ecological risk index (RI). Among the seven heavy metals, As and Cd were highly polluted, with Cd being the main contributor to potential ecological risks. Principal component analysis (PCA) was employed to identify the sources of the different heavy metals, revealing that As originated primarily from anthropogenic emissions, while Cd was primarily from atmospheric deposition. To further analyze the influence of water quality indicators on heavy metal pollution, an artificial neural network (ANN) model was utilized. A modified model was proposed, incorporating biochemical parameters to predict the level of heavy metal pollution, achieving an accuracy of 95.1%. This accuracy was 22.5% higher than that of the traditional model and particularly effective in predicting the maximum 20% of values. Results in this paper highlight the pollution of As and Cd along the YRE, and the proposed model provides valuable information for estimating heavy metal pollution in estuarine water environments, facilitating pollution prevention efforts.

Breaking the poverty trap in an ecologically fragile region through ecological engineering: A close-up look at long-term changes in ecosystem services.

Ecological vulnerability and poverty are interrelated and must be addressed together. The resolution of this issue will help us to meet the challenges during the process of implementing concrete actions for realizing the 2030 UN sustainable development goals (SDGs). Ecological restoration projects (ERPs) can enhance ecosystem services (ESs) while providing policy support for improving people's livelihoods. However, processes and mechanisms of ERPs on the ecological environment and socioeconomic development in poverty-stricken and ecologically fragile areas have rarely been studied. To address these issues, we conducted a comparative analysis on the changes of land use and land cover (LULC), ecosystem services (ESs), and socioeconomic development in Bijie City, a karst rocky desertification area in southwest China, before and after the implementation of ERPs in 2000, as well as the complex relationship between these factors. ERPs have affected LULCs, ESs, socioeconomics, and poverty reduction significantly since 2000. Specifically, the total ecosystem service value (ESV) in the study area has increased by more than 3 times in the past 30 years, with the ESV of tourism services and carbon storage increasing the most, from CNY 0.001 and 337.07 billion in 1990 to CNY 11.07 and 108.97 billion in 2019, respectively. The correlation between ESs is mainly synergistic, while the tradeoff between carbon storage and water yield is in a fluctuating upward trend. LULC conversion of cropland to green, and cropland to water, wetland and shrubs has positive effects on carbon storage and water yield, respectively. During study period, GDP, urbanization increased by over 70 times, 5 times, respectively, whereas poverty population, poverty incidence, and employment rate of various sectors (i.e., agriculture, forest, animal, and fishery, or AFAF) decreased by 96.4%, 97.7%, and 18.24%, respectively. Our findings emphasized that ERPs can effectively help poor and ecologically fragile areas to get out of the poverty trap and achieve the "win-win" goals of ecological and socio-economic sustainable development. These results have profound environmental management references to China and other developing countries around the world in realizing ecological restoration, poverty reduction, and the SDGs.

Probiotic consumption and hepatic steatosis: results from the NHANES 2011-2016 and Mendelian randomization study.

Background: Recent research showed that probiotics treatment may reduce insulin resistance, regulate lipid metabolism, raise liver enzyme levels, and ameliorate inflammation in individuals with metabolic associated fatty liver disease (MAFLD). However, the possible effects of probiotic use on the progression of hepatic steatosis (HS) have not been identified. The purpose of this study was to investigate this in a large population database. Methods: The cross-sectional research was conducted among adults with complete data on probiotic yogurt consumption and HS in the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Probiotic yogurt consumption was assessed using a dietary supplement questionnaire, while HS was evaluated with HS index (HSI). To explore their relationship, weighted univariate regression analysis, subgroup analysis, and interaction analysis were conducted. To evaluate the causal association between yogurt consumption and NAFLD, mendelian randomization analysis (MR) were performed. A restricted cubic spline (RCS) was used to analyze the relationship curve between the leves of yogurt consumption and hepatic steatosis. Results: A total of 7,891 participants were included in the study represented 146.7 million non-institutionalized residents of the United States, of whom 4,322 (54.77%) were diagnosed with HS. Multivariable logistic regression showed probiotic yogurt consumption had significantly inverse relationship for HS (OR = 0.84, 95% CI: 0.72-0.97, p = 0.02) after adjusting for all covariates. Once more, the independent relationship between probiotic yogurt consumption and HS was verified by subgroup analysis and interaction analysis. The MR analysis results indicate that there is no causal relationship between yogurt consumption and NAFLD. The RCS model demonstrated a robust J-shaped link between yogurt consumption and HS, revealing a significant decrease in risk within the lower range of yogurt consumption, which attained the lowest risk close to 0.4 cup. Conclusion: According to the NHANES data, the consumption of probiotics and yogurt has a beneficial effect on HS, whereas the MR results indicated it was not related to NAFLD. The RCS analysis indicates a J-shaped relationship between yogurt consumption and HS, which may account for the inconsistency in the results. Based on these findings, we recommend that adults take half a cup of yogurt daily.

Typical antibiotic resistance genes and their association with driving factors in the coastal areas of Yangtze River Estuary.

The massive use of antibiotics has led to the escalation of microbial resistance in aquatic environment, resulting in an increasing concern regarding antibiotic resistance genes (ARGs), posing a serious threat to ecological safety and human health. In this study, surface water samples were collected at eight sampling sites along the Yangtze River Estuary. The seasonal and spatial distribution patterns of 10 antibiotics and target genes in two major classes (sulfonamides and tetracyclines) were analyzed. The findings indicated a high prevalence of sulfonamide and tetracycline resistance genes along the Yangtze River Estuary. Kruskal-Wallis analysis revealed significant seasonal variations in the abundance of all target genes. The accumulation of antibiotic resistance genes in the coastal area of the Yangtze River Estuary can be attributed to the influence of urban instream runoff and the discharge of effluents from wastewater treatment plants. ANISOM analysis indicated significant seasonal differences in the microbial community structure. VPA showed that environmental factors contribute the most to ARG variation. PLS-PM demonstrate that environmental factors and microbial communities pose direct effect to ARG variation. Analysis of driving factors influencing ARGs in this study may shed new insights into the mechanism of the maintenance and propagation of ARGs.

Carbon fluxes of China's coastal wetlands and impacts of reclamation and restoration.

Coastal wetlands play an important role in regulating atmospheric carbon dioxide (CO2) concentrations and contribute significantly to climate change mitigation. However, climate change, reclamation, and restoration have been causing substantial changes in coastal wetland areas and carbon exchange in China during recent decades. Here we compiled a carbon flux database consisting of 15 coastal wetland sites to assess the magnitude, patterns, and drivers of carbon fluxes and to compare fluxes among contrasting natural, disturbed, and restored wetlands. The natural coastal wetlands have the average net ecosystem exchange of CO2 (NEE) of -577 g C m-2 year-1, with -821 g C m-2 year-1 for mangrove forests and -430 g C m-2 year-1 for salt marshes. There are pronounced latitudinal patterns for carbon dioxide exchange of natural coastal wetlands: NEE increased whereas gross primary production (GPP) and respiration of ecosystem decreased with increasing latitude. Distinct environmental factors drive annual variations of GPP between mangroves and salt marshes; temperature was the dominant controlling factor in salt marshes, while temperature, precipitation, and solar radiation were co-dominant in mangroves. Meanwhile, both anthropogenic reclamation and restoration had substantial effects on coastal wetland carbon fluxes, and the effect of the anthropogenic perturbation in mangroves was more extensive than that in salt marshes. Furthermore, from 1980 to 2020, anthropogenic reclamation of China's coastal wetlands caused a carbon loss of ~3720 Gg C, while the mangrove restoration project during the period of 2021-2025 may switch restored coastal wetlands from a carbon source to carbon sink with a net carbon gain of 73 Gg C. The comparison of carbon fluxes among these coastal wetlands can improve our understanding of how anthropogenic perturbation can affect the potentials of coastal blue carbon in China, which has implications for informing conservation and restoration strategies and efforts of coastal wetlands.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Comparison of Two Surgical Approaches for Periacetabular Osteotomy: A Retrospective Study of Patients with Developmental Dysplasia of the Hip.

OBJECTIVE: Given the intricate challenges and potential complications associated with periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH). Our study aimed to compare the clinical and imaging benefits and drawbacks of two surgical approaches, the modified Stoppa combined iliac spine approach and the modified Smith-Peterson approach, for treating PAO and to provide guidance for selecting clinical approaches. METHODS: A retrospective analysis of 56 patients with 62 DDHs was conducted from June 2018 to January 2022. The experimental group underwent surgery via the modified Stoppa combined iliac spine approach, while the control group underwent surgery via the modified Smith-Peterson approach for periacetabular osteotomy and internal fixation. Basic statistical parameters, including age, sex, BMI, and preoperative imaging data, were analyzed. Differences in surgical time, intraoperative blood loss, and postoperative imaging data were compared, as were differences in preoperative and postoperative imaging data between the two groups. RESULTS: There were 28 hips in the experimental group and 34 in the control group. Moreover, there was no significant difference in the basic parameters between the experimental and control groups. Before and after the operation, for the LCE angle, ACE angle, and Tonnis angle, there was no significant difference in acetabular coverage (p > 0.05). However, there were significant differences between the two groups in terms of the above four indicators before and after the operation (p < 0.05). After the operation, the experimental group exhibited significant increases in both lateral and anterior acetabular coverage of the femoral head. However, the experimental group had longer operation times and greater bleeding volumes than did the control group. Despite this, the experimental group demonstrated significant advantages in protecting the lateral femoral cutaneous nerve compared to the control group. CONCLUSION: The modified Stoppa combined iliac spine approach can be considered a practical approach for PAO and is more suitable for patients with DDH who plan to be treated by one operation than the classic modified Smith-Peterson approach for PAO.

Nitrogen isotopic characteristics of aerosol ammonium in a Chinese megacity indicate the reduction from vehicle emissions during the lockdown period.

The role of agricultural versus vehicle emissions in urban atmospheric ammonia (NH3) remains unclear. The lockdown due to the outbreak of COVID-19 provided an opportunity to assess the role of source emissions on urban NH3. Concentrations and δ15N of aerosol ammonium (NH4+) were measured before (autumn in 2017) and during the lockdown (summer, autumn, and winter in 2020), and source contributions were quantified using SIAR. Despite the insignificant decrease in NH4+ concentrations, significantly lower δ15N-NH4+ was found in 2020 (0.6 ± 1.0‰ in PM2.5 and 1.4 ± 2.1‰ in PM10) than in 2017 (15.2 ± 6.7‰ in PM2.5), which indicates the NH3 from vehicle emissions has decreased by∼50% during the lockdown while other source emissions are less affected. Moreover, a reversed seasonal pattern of δ15N-NH4+ during the lockdown in Changsha has been revealed compared to previous urban studies, which can be explained by the dominant effect of non-fossil fuel emissions due to the reductions of vehicle emissions during the lockdown period. Our results highlight the effects of lockdown on aerosol δ15N-NH4+ and the importance of vehicle emissions to urban atmospheric NH3, providing conclusive evidence that reducing vehicle NH3 emissions could be an effective strategy to reduce PM2.5 in Chinese megacities.

Overexpressing lipid raft protein STOML2 modulates the tumor microenvironment via NF-κB signaling in colorectal cancer.

Colorectal cancer (CRC) is characterized by a complex tumor inflammatory microenvironment, while angiogenesis and immunosuppression frequently occur concomitantly. However, the exact mechanism that controls angiogenesis and immunosuppression in CRC microenvironment remains unclear. Herein, we found that expression levels of lipid raft protein STOML2 were increased in CRC and were associated with advanced disease stage and poor survival outcomes. Intriguingly, we revealed that STOML2 is essential for CRC tumor inflammatory microenvironment, which induces angiogenesis and facilitates tumor immune escape simultaneously both in vitro and in vivo. Moreover, tumors with STOML2 overexpression showed effective response to anti-angiogenesis treatment and immunotherapy in vivo. Mechanistically, STOML2 regulates CRC proliferation, angiogenesis, and immune escape through activated NF-κB signaling pathway via binding to TRADD protein, resulting in upregulation of CCND1, VEGF, and PD-L1. Furthermore, treatment with NF-κB inhibitor dramatically reversed the ability of proliferation and angiogenesis. Clinically, we also observed a strong positive correlation between STOML2 expression and Ki67, CD31, VEGFC and PD-1 of CD8+T cell expression. Taken together, our results provided novel insights into the role of STOML2 in CRC inflammatory microenvironment, which may present a therapeutic opportunity for CRC.

Predictions of heavy metal concentrations by physiochemical water quality parameters in coastal areas of Yangtze river estuary.

Due to the degradation-resistant and strong toxicity, heavy metals pose a serious threat to the safety of water environment and aquatic ecology. Rapid acquisition and prediction of heavy metal concentrations are of paramount importance for water resource management and environmental preservation. In this study, heavy metal concentrations (Cr, Ni, Cu, Pb, Zn, Cd) and physicochemical parameters of water quality including Temperature (Temp), pH, Oxygen redox potential (ORP), Dissolved oxygen (DO), Electrical conductivity (EC), Electrical resistivity (RES), Total dissolved solids (TDS), Salinity (SAL), Cyanobacteria (BGA-PE), and turbidity (NTU) were measured at seven stations in the Yangtze river estuary. Principal Component Analysis (PCA) and Spearman correlation analysis were employed to analyze the main factors and sources of heavy metals. Results of PCA revealed that the main sources of Cr, Ni, Zn, and Cd were steel industry wastewater, domestic and industrial sewage, whereas shipping and vessel emissions were typically considered sources of Pb and Cu. Spearman correlation analysis identified Temp, pH, ORP, EC, RES, TDS, and SAL as the key physicochemical parameters of water quality, exhibiting the strongest correlation with heavy metal concentrations in sediment and water samples. Based on these results, multiple linear regression as well as non-linear models (SVM and RF) were constructed for predicting heavy metal concentrations. The results showed that the results of the nonlinear model were more suitable for predicting the concentrations of most heavy metals than the linear model, with average R values of the SVM test set and RF test set being 0.83 and 0.90. The RF model showed better applicability for simulating the concentration of heavy metals along the Yangtze river estuary. It was demonstrated that non-linear research methods provided efficient and accurate predictions of heavy metal concentrations in a simple and rapid manner, thereby offering decision-making support for watershed managers.

Development and Validation of Nomograms to Predict Risk and Prognosis in Salivary Gland Carcinoma Patient with Distant Metastases.

Background: Salivary gland carcinoma (SGC) patients with distant metastasis (DM) are rare, and understanding this disease is insufficient. Nomograms can predict the prognostic probability of patients, while few studies have examined diagnostic and prognostic factors in SGC patients with DM. The purpose of this study was to establish and validate the risk and prognostic nomograms of SGC patients with DM. Methods: Based on the SEER database, we analyzed the data of SGC patients between 2004 and 2015. Logistic regression analyses and Cox proportional hazards regression analyses were used to identify risk and prognostic factors for DM in SGC patients. Based on the Akaike information criterion (AIC) value and likelihood ratio test, the best-fitting model was selected to build risk and prognostic nomograms, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) survival curves. ROC curves were also used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system. Results: 7418 SGC patients were included in the study, and 307 (4.14%) of them were diagnosed with DM. This study identified that there are variables (age ≥ 80, no-parotid gland primary site, histologic type of mucoepidermoid carcinoma and squamous cell carcinoma, T stage ≥ T2, N staged ≥ N1, histologic grade ≥ III, and tumor size ≥ 41 mm) associated with the occurrence of DM in SGC patients. Therefore, we constructed diagnostic and prognostic nomograms after incorporating these variables. ROC curves illustrated the better predictive efficacy of 2 nomograms over the AJCC staging system. DCA curves, calibration curves, and K-M survival curves showed that 2 nomograms can accurately predict the occurrence and prognosis of DM among SGC patients in training and validation sets. Conclusion: It was shown that the nomograms were highly discriminative in predicting the diagnosis and prognosis of SGC patients with DM, and could identify high-risk patients, thereby providing SGC patients with individualized treatment plans.

Fibular free flap necrosis after mandibular reconstruction surgery with osteoradionecrosis: Establishment and verification of an early warning model.

OBJECTIVE: Fibular free flap necrosis (FFFN) is the most common complication in patients with osteoradionecrosis (ORN) after mandibular reconstruction surgery. However, there are no effective forecasting tools at present. This research is aimed to establish and verify a nomogram model to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients. METHODS: A total of 193 ORN patients with mandibular reconstruction using fibular free flap (150 cases in the model group and 43 cases in the validation group) were enrolled in this study. In the model group, the variables were optimized by lasso regression. Then the prediction model was established by binary logistic regression analysis, and the nomogram was drawn. The bootstrap self-sampling method was used for internal verification. Moreover, 43 cases in the validation group were used for external validation. RESULTS: The results of lasso regression and binary logistic regression analysis showed that the radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and American society of anesthesiologists (ASA) III were the independent risk factors for FFFN after mandibular reconstruction surgery in ORNJ patients (P<0.05). Based on the above-mentioned risk factors, the nomogram model was established. The AUC values of the model group and the validation group were 0.936 and 0.964, respectively. The curve analysis showed that when the probability thresholds of the model group and the validation group were 5.699%∼98.229% and 0.413%∼99.721%, respectively. So the patient's clinical net profit rate was the highest. CONCLUSION: A nomogram combining the factors of radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and ASA III provided a comparatively effective way to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients, which has distinct applied clinical value.

Deciphering cell wall sensors enabling the construction of robust P. pastoris for single-cell protein production.

Single-cell protein (SCP) production in the methylotrophic yeast Pichia pastoris has the potential to achieve a sustainable protein supply. However, improving the methanol fermentation efficiency and reducing carbon loss has been a long-standing challenge with far-reaching scientific and practical implications. Here, comparative transcriptomics revealed that PAS_0305, a gene directly associated with cell wall thickness under methanol stress, can be used as a target for unlocking cell wall sensors. Intracellular trehalose accumulation confirmed that cell wall sensors were activated after knocking out PAS_0305, which resulted in increased cell wall permeability. Genome-wide signal perturbations were transduced through the HOG module and the CWI pathway, which was confirmed to connected by Pbs2-Mkk. As a consequence of CWI pathway activation, ΔPAS_0305 elicited a rescue response of cell wall remodeling by increasing the ß-1,3-glucan content and decreasing the chitin/mannose content. Remarkably, perturbations in global stress signals led to a fine-tuning of the metabolic network of ΔPAS_0305, resulting in a superior phenotype with highest crude protein and methanol conversion rate of 67.21% and 0.46 gDCW/g. Further genome-scale metabolic models were constructed to validate the experimental results, confirming that unlocking cell wall sensors resulted in maximized flux from methanol towards SCP and effectively addressing the issue of carbon loss in methanol fermentation. This work sheds new light on the potential of manipulating cellular signaling pathways to optimize metabolic networks and achieve exceptional phenotypic characteristics, providing new strategies for constructing versatile cell factories in P. pastoris.

Occurrence of sulfonamides and tetracyclines in the coastal areas of the Yangtze River (China) Estuary.

Antibiotics have attracted global attention due to the ecological risks to environment. In this paper, solid-phase extraction and ultra-performance liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) were utilized to analyze the fugitive characteristics of 10 antibiotics of sulfonamides (sulfadiazine, sulfamethazine, sulfadimidine, sulfathiazole, sulfapyridine, sulfamethoxazole) and tetracyclines (tetracycline, oxytetracycline, chlortetracycline and doxycycline) in the coastal waters and surfece sediments of the Yangtze River Estuary and the ecological risks of antibiotics in water were estimated using ecological risk assessment method. The results have showed that 7 of the 10 antibiotics were detected in the water, with total concentrations ranging from 0.652 to 434.47 ng/L. 8 antibiotics were detected in the sediment, with total concentrations ranging from 0.091 to 499.23 ng/g. The main antibiotic species detected in the sediment and water varied seasonally. Higher concentrations in spatially distributed areas where rivers meet and where human activities have a more significant impact. The ecological risks were found to be higher in spring and autumn than those in winter and summer. Spatial variation in individual microbial communities was not evident in the sediments. The relationship between antibiotics and microorganisms in the environment was predominantly positive. Physical and chemical factors were significantly correlated for both antibiotics and microbial communities. This study can provide research ideas for other types of antibiotics and provide a basis for the prevention of antimicrobial resistance (AMR).

Targeted degradation of naphthalene by peroxymonosulfate activation using molecularly imprinted biochar.

Polycyclic aromatic hydrocarbons (PAHs) in aquatic environments are threatening ecosystems and human health. In this work, an effective and environmentally friendly catalyst based on biochar and molecular imprinting technology (MIT) was developed for the targeted degradation of PAHs by activating peroxymonosulfate. The results show that the adsorption amount of naphthalene (NAP) by molecularly imprinted biochar (MIP@BC) can reach 82% of the equilibrium adsorption capacity within 5 min, and it had well targeted adsorption for NAP in the solution mixture of NAP, QL and SMX. According to the comparison between the removal rates of NAP and QL by MIP@BC/PMS or BC/PMS system in respective pure solutions or mixed solutions, the MIP@BC/PMS system can better resist the interference of competing pollutants (i.e., QL) compared to the BC/PMS system; that is, MIP@BC had a good ability to selectively degrade NAP. Besides, the removal rate of NAP by MIP@BC/PMS gradually decreased as pH increased. The addition of Cl- greatly promoted the targeted removal of NAP in the MIP@BC/PMS system, while HCO3- and CO32- both had an inhibitory effect. Furthermore, SO4•-, O2•- and 1O2 produced by BC activating PMS dominated the NAP degradation, and it was inferred that the vacated imprinted cavities after NAP degradation can continue to selectively adsorb NAP and this could facilitate the reusability of the material. This study can promote the research on the targeted degradation of PAHs through the synergism of biochar/PMS advanced oxidation processes and MIT.

Economical production of Pichia pastoris single cell protein from methanol at industrial pilot scale.

BACKGROUND: Methanol, synthesized from CO2, is a potentially sustainable one-carbon (C1) resource for biomanufacturing. The use of methanol as a feedstock to produce single cell protein (SCP) has been investigated for decades as an alternative to alleviate the high global demand for animal-derived proteins. The methylotrophic yeast Pichia pastoris is an ideal host for methanol-based SCP synthesis due to its natural methanol assimilation ability. However, improving methanol utilization, tolerance to higher temperature, and the protein content of P. pastoris are also current challenges, which are of great significance to the economical industrial application using methanol as a feedstock for SCP production. RESULTS: In the present work, adaptive laboratory evolution (ALE) has been employed to overcome the low methanol utilization efficiency and intolerance to a higher temperature of 33 °C in P. pastoris, associated with reduced carbon loss due to the lessened detoxification of intracellular formaldehyde through the dissimilation pathway and cell wall rearrangement to temperature stress resistance following long-term evolution as revealed by transcriptomic and phenotypic analysis. By strengthening nitrogen metabolism and impairing cell wall synthesis, metabolic engineering further increased protein content. Finally, the engineered strain via multi-strategy produced high levels of SCP from methanol in a pilot-scale fed-batch culture at 33 °C with a biomass of 63.37 g DCW/L, methanol conversion rate of 0.43 g DCW/g, and protein content of 0.506 g/g DCW. SCP obtained from P. pastoris contains a higher percentage of protein compared to conventional foods like soy, fish, meat, whole milk, and is a source of essential amino acids, including methionine, lysine, and branched-chain amino acids (BCAAs: valine, isoleucine, leucine). CONCLUSIONS: This study clarified the unique mechanism of P. pastoris for efficient methanol utilization, higher temperature resistance, and high protein synthesis, providing a P. pastoris cell factory for SCP production with environmental, economic, and nutritional benefits.

An endoplasmic reticulum stress-related signature could robustly predict prognosis and closely associate with response to immunotherapy in pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Endoplasmic reticulum stress (ERS) plays an essential role in PDAC progression. Here, we aim to identify the ERS-related genes in PDAC and build reliable risk models for diagnosis, prognosis and immunotherapy response of PDAC patients as well as investigate the potential mechanism. METHODS: We obtained PDAC cohorts with transcriptional profiles and clinical data from the ArrayExpress, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Univariate Cox regression, LASSO regression and multivariate Cox regression analyses were used to construct an ERS-related prognostic signature. The CIBERSORT and ssGSEA algorithms were applied to explore the correlation between the prognostic signature and immune cell infiltration and immune-related pathways. The GDSC database and TIDE algorithm were used to predict responses to chemotherapy and immunotherapy, identifying potential drugs for treating patients with PDAC. RESULTS: We established and validated an ERS-related prognostic signature comprising eight genes (HMOX1, TGFB1, JSRP1, GAPDH, CAV1, CHRNE, CD74 and ERN2). Patients with higher risk scores displayed worse outcomes than those with lower risk scores. PDAC patients in low-risk groups might benefit from immunotherapy. Dasatinib and lapatinib might have potential therapeutic implications in high-risk PDAC patients. CONCLUSION: We established and validated an ERS-related prognostic signature comprising eight genes to predict the overall survival outcome of PDAC patients, which closely correlating with the response to immunotherapy and sensitivity to anti-tumor drugs, as well as could be beneficial for formulating clinical strategies and administering individualized treatments.

Temporal dynamics of ecosystem, inherent, and underlying water use efficiencies of forests, grasslands, and croplands and their responses to climate change.

BACKGROUND: Understanding temporal trends and varying responses of water use efficiency (WUE) to environmental changes of diverse ecosystems is key to predicting vegetation growth. WUE dynamics of major ecosystem types (e.g., forest, grassland and cropland) have been studied using various WUE definitions/metrics, but a comparative study on WUE dynamics and their driving forces among different ecosystem types using multiple WUE metrics is lacking. We used eddy covariance measurements for 42 FLUXNET2015 sites (396 site years) from 1997 to 2014, as well as three commonly used WUE metrics (i.e., ecosystem, inherent, and underlying WUE) to investigate the commonalities and differences in WUE trends and driving factors among deciduous broadleaf forests (DBFs), evergreen needleleaf forests (ENFs), grasslands, and croplands. RESULTS: Our results showed that the temporal trends of WUE were not statistically significant at 73.8% of the forest, grassland and cropland sites, and none of the three WUE metrics exhibited better performance than the others in quantifying WUE. Meanwhile, the trends observed for the three WUE metrics were not significantly different among forest, grassland and cropland ecosystems. In addition, WUE was mainly driven by atmospheric carbon dioxide concentration at sites with significant WUE trends, and by vapor pressure deficit (VPD) at sites without significant trends (except cropland). CONCLUSIONS: Our findings revealed the commonalities and differences in the application of three WUE metrics in disparate ecosystems, and further highlighted the important effect of VPD on WUE change.

Long-term satellite observations show continuous increase of vegetation growth enhancement in urban environment.

Urbanization shows continuous expansion and development, ushering in the co-evolution of urban environments and vegetation over time. Recent remote sensing-based studies have discovered prevalent vegetation growth enhancement in urban environments. However, whether there is a temporal evolution of the growth enhancement remains unknown and unexplored. Here we expanded the existing framework for assessing the long-term impact of urbanization on vegetation greenness (enhanced vegetation index, EVI) using long time series of remote sensing images and applied it in Changsha, the capital city of Hunan province in China. Results showed that vegetation growth experienced widespread enhancement from 2000 to 2017, and increased 1.8 times from 2000 to 2017, suggesting strong continuous adaptive capability of vegetation to urban conditions. Although the overall impact of urbanization was negative due to the replacement of vegetated surfaces, the growth enhancement nevertheless offset or compensated the direct loss of vegetated cover during urbanization in the magnitude of 28 % in 2000 to 44 % in 2017. Our study also revealed large spatial heterogeneity in vegetation growth response among various districts at different urbanization levels and found an emergent trend under the observed spatial heterogeneity toward an asymptotic maximum with urbanization, showing EVI converges to 0.22 in highly urbanized areas. We further found that the positive effect of urbanization on vegetation growth is a function of urbanization intensity and time, which implies that the effect of the urban environment on vegetation can be simulated and predicted, and can be verified in more cities in the future. Our study is the first to successfully quantify long-term spatial patterns on the co-evolution of urbanization and vegetation, providing a new understanding of the continuous adaptive responses of vegetation growth to urbanization and shedding light on predicting biological responses to future environmental change.

The Utility of Peripherally Restricted Kappa-Opioid Receptor Agonists for Inhibiting Below-Level Pain After Spinal Cord Injury in Mice.

Pain after spinal cord injury (SCI) can be difficult to treat. Drugs that target the opioid receptor (OR) outside the central nervous system (CNS) have gained increasing interest in pain control owing to their low risk of central side effects. Asimadoline and ICI-204448 are believed to be peripherally restricted KOR agonists withlimited access to the CNS. This study examined whether they can attenuate pain hypersensitivity in mice subjected to a contusive T10 SCI. Subcutaneous (s.c.) injection of asimadoline (5, 20 mg/kg) and ICI-204448 (1, 10 mg/kg) inhibited heat hypersensitivity at both doses, but only attenuated mechanical hypersensitivity at the high dose. However, the high-dose asimadoline adversely affected animals' exploratory performance in SCI mice and caused aversion, suggesting CNS drug penetration. In contrast, high-dose ICI-204448 did not impair exploration and remained effective in reducing both mechanical and heat hypersensitivities after SCI. Accordingly, we chose to examine the potential peripheral neuronal mechanism for ICI-204448-induced pain inhibition by conducting in vivo calcium imaging of dorsal root ganglion (DRG) in Pirt-GCaMP6s+/- mice. High-dose ICI-204448 (10 mg/kg, s.c.) attenuated the increased fluorescence intensity of lumbar DRG neurons activated by a noxious pinch (400 g) stimulation in SCI mice. In conclusion, systemic administration of ICI-204448 achieved SCI pain inhibition at doses that did not induce notable side effects and attenuated DRG neuronal excitability which may partly contribute to its pain inhibition. These findings suggest that peripherally restricted KOR agonists may be useful for treating SCI pain, but the therapeutic window must be carefully examined.