Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.

Critical review on salt tolerance improvement and salt accumulation inhibition strategies of osmotic membrane bioreactors.

The osmotic Membrane Bioreactor (OMBR) is a novel wastewater treatment and resource recovery technology combining forward osmosis (FO) and membrane bioreactor (MBR). It has attracted attention for its low energy consumption and high contaminant removal performance. However, in the long-term operation, OMBR faces the problem of salt accumulation due to high salt rejection and reverse salt flux, which affects microbial activity and contaminants removal efficiency. This review analyzed the feasibility of screening salt-tolerant microorganisms and determining salinity thresholds to improve the salt tolerance of OMBR. Combined with recent research, the inhibition strategies for salt accumulation were reviewed, including the draw solution, FO membrane, operating conditions and coupling with other systems. It is hoped to provide a theoretical basis and practical guidance for the further development of OMBR. Finally, future research directions were prospected. This review provided new insights for achieving stable operation of OMBR and will promote its wide application.

KLRG1-expressing CD8+ T cells are exhausted and polyfunctional in patients with chronic hepatitis B.

Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.

Insight into the microbial community of denitrification process using different solid carbon sources: Not only bacteria.

There is a lack of understanding about the bacterial, fungal and archaeal communities' composition of solid-phase denitrification (SPD) systems. We investigated four SPD systems with different carbon sources by analyzing microbial gene sequences based on operational taxonomic unit (OTU) and amplicon sequence variant (ASV). The results showed that the corncob-polyvinyl alcohol sodium alginate-polycaprolactone (CPSP, 0.86±0.04 mg NO3--N/(g·day)) and corncob (0.85±0.06 mg NO3--N/(g·day)) had better denitrification efficiency than polycaprolactone (PCL, 0.29±0.11 mg NO3--N/(g·day)) and polyvinyl alcohol-sodium alginate (PVA-SA, 0.24±0.07 mg NO3--N/(g·day)). The bacterial, fungal and archaeal microbial composition was significantly different among carbon source types such as Proteobacteria in PCL (OTU: 83.72%, ASV: 82.49%) and Rozellomycota in PVA-SA (OTU: 71.99%, ASV: 81.30%). ASV methods can read more microbial units than that of OTU and exhibit higher alpha diversity and classify some species that had not been identified by OTU such as Nanoarchaeota phylum, unclassified_ f_ Xanthobacteraceae genus, etc., indicating ASV may be more conducive to understand SPD microbial communities. The co-occurring network showed some correlation between the bacteria fungi and archaea species, indicating different species may collaborate in SPD systems. Similar KEGG function prediction results were obtained in two bioinformatic methods generally and some fungi and archaea functions should not be ignored in SPD systems. These results may be beneficial for understanding microbial communities in SPD systems.

Carbon wet deposition flux and river carbon output in a forest watershed in permafrost region of the Da Xing'an Mountains.

Carbon wet deposition and river carbon output in river basins are important components of global carbon cycle. The assessment of both properties is of great significance for regional carbon budget. However, research on these topics in high-latitude permafrost regions in China is still lacking. We conducted dynamic monitoring of carbon wet deposition and carbon output in the river from May 28th to October 30th, 2022, in Laoyeling watershed, a typical forested watershed in the Da Xing'an Mountains permafrost region. We analyzed the variations of carbon component concentrations and fluxes in precipitation and river water, and estimated the contribution of carbon wet deposition to carbon output in the watershed. The results showed that wet deposition fluxes of dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and total dissolved carbon (TDC) in the Laoyeling watershed were 1354.86, 684.59, and 2039.45 kg·km-2, respectively. The fluxes of DOC, DIC, TDC, particulate organic carbon (POC), particulate inorganic carbon (PIC), and total carbon (TC) in the river were 601.75, 1977.30, 2579.05, 125.13, 21.99, and 2726.17 kg·km-2, respectively. The contribution of TDC wet deposition to the river TDC output was 9941.89 kg, accounting for 17.6% of total output. The DIC concentration in the river showed significant seasonal differences, with increased runoff resulting from precipitation leading to a decrease in DIC concentration in the river and showing a clear dilution effect, while the concentrations of DOC, POC, and PIC increased, mainly due to erosion effect. In conclusion, carbon wet deposition flux in the Laoyeling watershed was mainly determined by precipitation, and its contribution to river carbon output was relatively small compared to other factor. Runoff was the dominant factor affecting river carbon output. The results would provide important insights into carbon cycling and carbon budget balance in permafrost regions under climate change.

Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its nutrient-scavenging ability, crucial for tumor progression. Here, we investigated the roles of caveolae-mediated endocytosis (CME) in PDAC progression. Analysis of patient data across diverse datasets revealed a strong association of high caveolin-1 (Cav-1) expression with higher histologic grade, the most aggressive PDAC molecular subtypes, and worse clinical outcomes. Cav-1 loss markedly promoted longer overall and tumor-free survival in a genetically engineered mouse model. Cav-1-deficient tumor cell lines exhibited significantly reduced proliferation, particularly under low nutrient conditions. Supplementing cells with albumin rescued the growth of Cav-1-proficient PDAC cells, but not in Cav-1-deficient PDAC cells under low glutamine conditions. In addition, Cav-1 depletion led to significant metabolic defects, including decreased glycolytic and mitochondrial metabolism, and downstream protein translation signaling pathways. These findings highlight the crucial role of Cav-1 and CME in fueling pancreatic tumorigenesis, sustaining tumor growth, and promoting survival through nutrient scavenging.

Research on the Application and Mechanisms of Electroactive Microorganisms in Toxicants Monitoring: A Review.

A biological treatment is the core process for removing organic pollutants from industrial wastewater. However, industrial wastewater often contains large amounts of toxic and harmful pollutants, which can inhibit the activity of microorganisms in a treatment system, precipitate the deterioration of effluent quality, and threaten water ecological security from time to time. In most of the existing anaerobic biological treatment processes, toxic effects on microorganisms are determined according to the amounts of end-products of the biochemical reactions, and the evaluation results are relatively lacking. When microorganisms contact toxic substances, changes in biological metabolic activity precede the accumulation of reaction products. As sensitive units, electroactive microorganisms can generate electrical signals, a change in which can directly reflect the toxicity level. The applications of electroactive microorganisms for the toxicity monitoring of wastewater are very promising. Further attention needs to be paid to considering the appropriate evaluation index, the influence of the environment on test results, mechanisms, and other aspects. Therefore, we reviewed the literature regarding the above aspects in order to provide a research foundation for the practical application of electroactive microorganisms in toxicant monitoring.

Long non-coding RNA DANCR increases spinal cord neuron apoptosis and inflammation of spinal cord injury by mediating the microRNA-146a-5p/MAPK6 axis.

OBJECTIVE: This research was to unravel the impact of the lncRNA differentiation antagonizing non-protein coding RNA (DANCR)/microRNA (miR)-146a-5p/mitogen-activated protein kinase 6 (MAPK6) axis on spinal cord injury (SCI). METHODS: SCI mouse models were established and injected with si-DANCR or miR-146a-5p agomir. The recovery of motor function was assessed by Basso Mouse Scale. SCI was pathologically evaluated, and serum inflammatory factors were measured in SCI mice. Mouse spinal cord neurons were injured by H2O2 and transfected, followed by assessment of proliferation and apoptosis. DANCR, miR-146a-5p, and MAPK6 in tissues and cells were detected, as well as their relationship. RESULTS: DANCR increased and miR-146a-5p decreased in SCI. Silencing DANCR or enhancing miR-146a-5p stimulated the proliferation of mouse spinal cord neurons and reduced apoptosis. DANCR was bound to miR-146a-5p to target MAPK6. DANCR affected the proliferation and apoptosis of spinal cord neurons by mediating the miR-146a-5p/MAPK6 axis. Downregulating DANCR or upregulating miR-146a-5p improved inflammation, the destruction of spinal cord tissue structure, and apoptosis in SCI mice. CONCLUSION: DANCR affects spinal cord neuron apoptosis and inflammation of SCI by mediating the miR-146a-5p/MAPK6 axis.

Food therapy of scutellarein ameliorates pirarubicin­induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress.

Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart­related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti­inflammatory, antioxidant, cardio­cerebral vascular protective and anti­apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP­induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin­1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.

Differences in greenhouse gas emissions and microbial communities between underground and conventionally constructed wastewater treatment plants.

Large quantities of greenhouse gases (GHGs) are emitted into the atmosphere during wastewater treatment. In this study, GHG and microbial samples were collected from four wastewater treatment plants (WWTPs), and their differences and relationships were assessed. The study showed that, compared with conventionally constructed WWTPs, well-established gas collection systems in underground WWTPs facilitate comprehensive collection and accurate accounting of GHGs. In aboveground WWTPs, capped anoxic ponds promote methane production releasing it at 2-8 times the rate of uncapped emissions, in contrast to nitrous oxide emissions. Moreover, a stable subsurface environment allows for smaller fluctuations in daily GHG emissions and higher microbial diversity and abundance. This study highlights differences in GHG emission fluxes and microbial communities in differently constructed WWTPs, which are useful for control and accurate accounting of GHG emissions.

Fabrication of the flower-like Z-scheme heterojunction photocatalyst Bi-BiOI/UiO 66 for enhanced photodegradation of acetaminophen in simulated wastewater.

Acetaminophen is a representative contaminant of emerging persistent organic pollutants that can cause environmental problems when it enters municipal wastewater. An innovative flower-like Z-scheme photocatalyst Bi-BiOI/UiO 66 heterojunction composite was designed and constructed via a one-step solvothermal method. Investigations demonstrated that the Z-scheme structure strongly contributes to increasing the degradation efficiency of micropollutants. The results indicate that the bandgap energy (Eg) of the Bi-BiOI/UiO 66 composite decreases significantly from 3.22 eV to 2.43 eV, in comparison with that of pure copper-based UiO 66. Under suitable conditions (5 mg/L Ace, pH 3, 0.05 g/L), the organic pollutants in the water can be removed completely. A k value of 5.67 × 10-2 min-1 for the Bi-BiOI/UiO 66 heterojunction composite was found to effectively represent the acetaminophen photodegradation process. The reaction mechanism of acetamide in aqueous solution is also discussed. The Bi in Bi-BiOI can use surface plasmon resonance to form an electric field and accelerate the separation of photogenerated electrons and holes. This study highlights the potential of a novel photocatalyst for practical application.

Simultaneous Wastewater Treatment and Resources Recovery by Forward Osmosis Coupled with Microbial Fuel Cell: A Review.

Osmotic microbial fuel cells (OsMFCs) with the abilities to simultaneously treat wastewater, produce clean water, and electricity provided a novel approach for the application of microbial fuel cell (MFC) and forward osmosis (FO). This synergistic merging of functions significantly improved the performances of OsMFCs. Nonetheless, despite their promising potential, OsMFCs currently receive inadequate attention in wastewater treatment, water reclamation, and energy recovery. In this review, we delved into the cooperation mechanisms between the MFC and the FO. MFC facilitates the FO process by promoting water flux, reducing reverse solute flux (RSF), and degrading contaminants in the feed solution (FS). Moreover, the water flux based on the FO principle contributed to MFC's electricity generation capability. Furthermore, we summarized the potential roles of OsMFCs in resource recovery, including nutrient, energy, and water recovery, and identified the key factors, such as configurations, FO membranes, and draw solutions (DS). We prospected the practical applications of OsMFCs in the future, including their capabilities to remove emerging pollutants. Finally, we also highlighted the existing challenges in membrane fouling, system expansion, and RSF. We hope this review serves as a useful guide for the practical implementation of OsMFCs.

Survival comparison of pulmonary neuroendocrine carcinoma, adenocarcinoma with neuroendocrine differentiation, and adenocarcinoma.

Background: Pulmonary adenocarcinoma with neuroendocrine differentiation (ADE_ned) is a relatively uncommon pathological classification, and there exists considerable debate regarding its prognosis and treatment. The purpose of this study was to analyze the survival difference between patients with neuroendocrine carcinoma (NEC), adenocarcinoma (ADE), or ADE_ned and to investigate the prognostic factors influencing the outcomes of individuals diagnosed with pulmonary ADE_ned. Methods: We retrieved information on 316 cases of ADE_ned, 188,823 cases of ADE, and 71,154 cases of NEC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. To account for potential confounding variables, propensity score matching (PSM) was employed. Comparative analyses were conducted to estimate the overall survival (OS) and cancer-specific survival (CSS). Finally, the Cox regression models were used to identify prognostic factors associated with pulmonary ADE_ned. Results: Prior to PSM, patients with lung ADE_ned had a worse OS rate than did those with lung ADE or NEC (5-year OS rate: 13.3% vs. 26.6% vs. 15.6%; P<0.001 and P=0.009, respectively). In terms of CSS, the 5-year CSS rate of patients with ADE_ned was superior to that of NEC but inferior to that of ADE (28.7% vs. 26.8% vs. 43.8%; P=0.006 and P<0.001, respectively). Following PSM, the 5-year survival rate of patients with ADE_ned remained lower than that of individuals with ADE or NEC in terms of OS (13.3% vs. 24.4% vs. 23.0%; P<0.001 and P<0001, respectively) and CSS (28.8% vs. 58.6% vs. 43.1%; P<0.001 and P=0.006, respectively). Finally, the results of the competitive risk regression analysis demonstrated that several variables, including sex, T stage, N stage, M stage, and surgery, were found to be independent prognostic factors for patients diagnosed with pulmonary ADE_ned (all P values <0.05). Conclusions: Patients with lung ADE_ned had a significantly poorer survival outcome compared to those with lung ADE or NEC. Furthermore, sex, tumor-node-metastasis (TNM) stage, and surgery were found to be independent prognostic indicators for cases with lung ADE_ned.

Various solitons induced by relative phase in the nonlinear Schrödinger Maxwell-Bloch system.

We study the effect of relative phase on the characteristics of rogue waves and solitons described by rational solutions in the nonlinear Schrödinger Maxwell-Bloch system. We derived the rational rogue wave and soliton solutions with adjustable relative phase and present the parameter range of different types of rogue waves and solitons. Our findings show that the relative phase can alter the distribution of rational solitons and even change the type of rational solitons, leading to a rich array of rational soliton types by adjusting the relative phase. However, the relative phase does not affect the structure of the rogue wave, because the relative phase of the rogue wave changes during evolution. In particular, we confirm that the rational solitons with varying relative phases and the rogue waves at corresponding different evolution positions share the same distribution mode. This relationship holds true for rogue waves or breathers and their stable counterparts solitons or periodic waves in different nonlinear systems. The implications of our study are significant for exploring fundamental excitation elements in nonlinear systems.

The Application of Membrane Separation Technology in the Pharmaceutical Industry.

With the advancement in membrane technology, membrane separation technology has been found increasingly widespread applications in the pharmaceutical industry. It is utilized in drug separation and purification, wastewater treatment, and the recycling of wastewater resources. This study summarizes the application history of membrane technology in the pharmaceutical industry, presents practical engineering examples of its applications, analyzes the various types of membrane technologies employed in the pharmaceutical sector, and finally, highlights the application cases of renowned international and Chinese membrane technology companies in the pharmaceutical field.

Mitigation of reverse osmosis membrane fouling by coagulation pretreatment to remove silica and transparent exopolymer particles.

The dissolution of silica and transparent exopolymer particles (TEP) can deposit on the membrane surface and cause serious membrane fouling in reverse osmosis (RO) technology. Coagulation, as a common pretreatment process for RO, can effectively intercept pollutants and alleviate membrane fouling. In this study, FeCl3 and AlCl3 coagulants and polyacrylamide (PAM) flocculants were used to explore the optimal coagulation conditions to reduce the concentration of silica and TEP in the RO process. The results showed that the two coagulants had the best removal effect on pollutants when the pH was 7 and the dosage was 50 mg/L. Considering the proportion of reversible fouling after coagulation, the removal rate of pollutants, and the residual amount of coagulation metal ions, the best PAM dosage was 5 mg/L for FeCl3 and 1 mg/L for AlCl3. After coagulation pretreatment, the Zeta potential decreased, and the particle size distribution increased, making pollutants tend to aggregate, thus effectively removing foulants. The removal mechanisms of pollutants by coagulation pretreatment were determined to be adsorption, electric neutralization and co-precipitation. This study determined the best removal conditions of silica and TEP by coagulation and explored the removal mechanism.

Impact analysis of operating conditions on carbon dioxide reduction in microbial electrosynthesis: Insight into the substance utilization and microbial response.

Microbial electrosynthesis (MES) is facing a series of problems including low energy utilization and production efficiency of high value-added products, which seriously hinder its practical application. In this study, a more practical direct current power source was used and the anaerobic activated sludge from wastewater treatment plants was inoculated to construct the acetic acid-producing MES. The operating conditions of acetic acid production were further optimized and the specific mechanisms involving the substance utilization and microbial response were revealed. The optimum conditions were the potential of 3.0 V and pH 6.0. Under these conditions, highly electroactive biofilms formed and all kinds of substances were effectively utilized. In addition, dominant bacteria (Acetobacterium, Desulfovibrio, Sulfuricurvum, Sulfurospirillum, and Fusibacter) had high abundances. Under optimal conditions, acetic acid-forming characteristic genera (Acetobacterium) had the highest relative abundance (Biocathode-25.82 % and Suspension-17.24 %). This study provided references for the optimal operating conditions of MES and revealed the corresponding mechanisms.

Differences in the Effect of Mn2+ on the Reverse Osmosis Membrane Fouling Caused by Different Types of Organic Matter: Experimental and Density Functional Theory Evidence.

Landfill leachate from some sites contains a high concentration of Mn2+, which may cause reverse osmosis (RO) membrane fouling during RO treatment. In this study, the effect of Mn2+ on RO membrane fouling caused by typical organic pollutants (humic acid (HA), protein (BSA), and sodium alginate (SA)) was systematically investigated, and it was found that Mn2+ exacerbates RO membrane fouling caused by HA, SA, and HBS (mixture of HA + BSA + SA). When the Mn2+ concentration was 0.5 mM and 0.05 mM separately, the membrane fouling caused by HA and SA began to become significant. On the other hand, with for HBS fouling only, the water flux decreased significantly by about 21.7% and further decreased with an increasing Mn2+ concentration. However, Mn2+ has no direct effect on BSA. The effect degrees to which Mn2+ affected RO membrane fouling can be expressed as follows: HBS > SA > HA > BSA. The density functional theory (DFT) calculations also gave the same results. In modeling the reaction of the complexation of Mn2+ with the carboxyl group in these four types of organic matter, BSA has the highest energy (-55.7 kJ/mol), which predicts that BSA binding to Mn2+ is the most unstable compared to other organic matter. The BSA carboxylate group also has the largest bond length (2.538-2.574 Å) with Mn2+ and the weakest interaction force, which provides a theoretical basis for controlling RO membrane fouling exacerbated by Mn2+.

A Comprehensive Analysis of the Impact of Inorganic Matter on Membrane Organic Fouling: A Mini Review.

Membrane fouling is a non-negligible issue affecting the performance of membrane systems. Particularly, organic fouling is the most persistent and severe form of fouling. The complexation between inorganic and organic matter may exacerbate membrane organic fouling. This mini review systematically analyzes the role of inorganic matter in membrane organic fouling. Inorganic substances, such as metal ions and silica, can interact with organic foulants like humic acids, polysaccharides, and proteins through ionic bonding, hydrogen bonding, coordination, and van der Waals interactions. These interactions facilitate the formation of larger aggregates that exacerbate fouling, especially for reverse osmosis membranes. Molecular simulations using molecular dynamics (MD) and density functional theory (DFT) provide valuable mechanistic insights complementing fouling experiments. Polysaccharide fouling is mainly governed by transparent exopolymer particle (TEP) formations induced by inorganic ion bridging. Inorganic coagulants like aluminum and iron salts mitigate fouling for ultrafiltration but not reverse osmosis membranes. This review summarizes the effects of critical inorganic constituents on fouling by major organic foulants, providing an important reference for membrane fouling modeling and fouling control strategies.

Fusobacterium nucleatum-triggered neutrophil extracellular traps facilitate colorectal carcinoma progression.

BACKGROUND: Fusobacterium nucleatum (Fn) acts as a procarcinogenic bacterium in colorectal carcinoma (CRC) by regulating the inflammatory tumor microenvironment (TME). Neutrophil extracellular traps (NETs), which can be generated by persistent inflammation, have been recently considered to be significant contributors in promoting cancer progression. However, whether NETs are implicated in Fn-related carcinogenesis is still poorly characterized. Here, we explored the role of NETs in Fn-related CRC as well as their potential clinical significance. METHODS: Fn was measured in tissue specimens and feces samples from CRC patients. The expression of NET markers were also detected in tissue specimens, freshly isolated neutrophils and blood serum from CRC patients, and the correlation of circulating NETs levels with Fn was evaluated. Cell-based experiments were conducted to investigate the mechanism by which Fn modulates NETs formation. In addition, we clarified the functional mechanism of Fn-induced NETs on the growth and metastasis of CRC in vitro and in vivo experiments. RESULTS: Tissue and blood samples from CRC patients, particularly those from Fn-infected CRC patients, exhibited greater neutrophil infiltration and higher NETs levels. Fn infection induced abundant NETs production in in vitro studies. Subsequently, we demonstrated that Fn-induced NETs indirectly accelerated malignant tumor growth through angiopoiesis, and facilitated tumor metastasis, as manifested by epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinase (MMP)-mediated basement membrane protein degradation, and trapping of CRC cells. Mechanistically, the Toll-like receptor (TLR4)-reactive oxygen species (ROS) signaling pathway and NOD-like receptor (NOD1/2)-dependent signaling were responsible for Fn-stimulated NETs formation. More importantly, circulating NETs combined with carcinoembryonic antigen (CEA) could predict CRC occurrence and metastasis, with areas under the ROC curves (AUCs) of 0.92 and 0.85, respectively. CONCLUSIONS: Our findings indicated that Fn-induced NETs abundance by activating TLR4-ROS and NOD1/2 signalings in neutrophils facilitated CRC progression. The combination of circulating NETs and CEA was identified as a novel screening strategy for predicting CRC occurrence and metastasis.