Mainstream Treatment Research Articles

Mechanical Behavior of Polymer Braided Stent at Rapid Radial Loading

Stent implantation is the mainstream treatment for high-incidence vascular diseases. The stent is implanted into the blocked vessel with minimal trauma to restore blood flow. Polymer braided stents with superior biocompatibility and flexibility have broad application prospects in stent implantation. An ideal polymer stent should have suitable radial supporting capacity to withstand the cyclic radial load from vessels. Especially in the case of accelerated vasoconstriction caused by emotional excitement, drinking or fever, etc. However, there are currently limited studies on the mechanical properties of stent at rapid radial loading. In this work, the radial supporting capacity and fatigue properties of polymer stent at rapid loading rate were investigated by experiment and simulation. With the increase of radial loading rate, the stent has different deformation tendency and fatigue resistance. This study is helpful to study the structural changes of the polymer braided stent at different loading rates, and provide ideas for the evaluation and the optimization of the polymer braided stent.

Ascorbic acid predominantly kills cancer stem cell-like cells in the hepatocellular carcinoma cell line Li-7 and is more effective at low cell density and in small spheroids

The development of therapies that target cancer stem cells (CSCs) is an important challenge in cancer research. The antioxidant system is enhanced in CSCs, which may lead to resistance to existing therapies. Ascorbic acid (AA) has the potential to act as both an antioxidant and a pro-oxidant agent, but its effects on CSCs are a subject of current research. Here, we investigated the effect of AA focusing specifically on CSCs with the hepatocellular carcinoma cell line Li-7. The Li-7 cell line is heterogenous consisting of CD166- and CD166+ cells; CD166- cells include CSC-like cells (CD13+CD166- cells) and CD13−CD166- cells that can revert to CD13+CD166- cells. The addition of AA to the culture medium caused cell death in both cell populations in CD166- cells in a concentration dependent manner. In contrast, AA administration had a limited effect on CD166+ non-CSC cells. The level of reactive oxygen species after AA treatment was elevated only in CD166- cells. The effect of AA only occurred at low cell densities in 2D and 3D cultures. In a mouse tumor model injected with Li-7 cells, intraperitoneal administration of AA failed to prevent tumor formation but appeared to delay tumor growth. Our findings shed light on why AA administration has not become a mainstream treatment for cancer treatment; however, they also show the possibility that AA can be used in therapies to suppress CSCs.

Abstract 1179: A single-cell atlas of human gastric malignancy reveals CD8+ T cell rejuvenation as a mediator of immunotherapeutic response

Abstract Immune checkpoint inhibition (ICI) has emerged as a mainstream treatment for patients with advanced stage gastric cancer (GC). Cellular heterogeneity in the tumor microenvironment (TME) has a profound impact on the therapeutic responses to ICI. Here we characterize the kinetics of tumor-infiltrating immune populations in GC patients treated with anti-PD-1 using single-cell RNA and TCR sequencing (scRNA/TCR-seq), including primary tumors and metastases. Integrated with public GC scRNA-seq datasets, we construct the largest multi-omic atlas of GC cell states to date that captures the full trajectory of GC malignancy and comprises >320,000 cells derived from 73 samples. We demonstrate the rejuvenation of exhausted CD8+ T cells into a proliferative state marked by the loss of LAYN expression as a major mediator of ICI response in the TME. In parallel, we observe enhanced immunogenicity of cancer cells in post-ICI tumors, thus highlighting the coordination between tumor-intrinsic and microenvironmental factors elicited by ICI. Our study provides a valuable resource of investigating the tumor response to anti-PD-1 treatment and suggests novel strategies for combination therapy and patient stratification. Citation Format: Han Liang, Jian Chen, Yikai Luo, Muxing Kang, Wei Liu, Lie Wang. A single-cell atlas of human gastric malignancy reveals CD8+ T cell rejuvenation as a mediator of immunotherapeutic response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1179.

Abstract 5862: Retrotransposable elements mediate the drug-tolerant persistence in claudin-low breast cancer chemo-treatment

Abstract The emergence of acquired drug resistance through treatment remains a critical threat to efficient cancer therapies, which most often lead to relapse and metastasis. The development of resistance is an evolutionary adaptation process that heavily depends on tumor heterogeneity (underpinned by cellular plasticity). Therefore, a longitudinal deconvolution of treatment adaptation is critical to uncover the driving-force mechanisms underpinning resistance adaptation. In the clinic, chemotherapy remains the mainstream treatment for TNBC, and one of the primary chemo-agents is doxorubicin. Although the initial responsive rate of doxorubicin-based chemotherapies is up to 70%, it is well recognized that TNBC cells usually generate an adaptive response and result in acquired drug-resistance and multi-drug resistant phenotypes. Although numerous mechanisms of chemo-resistance evolution have been proposed, most of these studies focused on the initial and terminal states, from which we could not deconvolute the adaptation routes and might miss the transient fate-switching events. We hypothesize that the claudin-low TNBC chemo-resistant cells may derive from the early-stage reversible chemo-tolerant persistent state, and early-stage state-switching mediated by epigenetic landscape reprogramming might determine the adaptation through treatment. We developed an in vitro “pulsing-treatment” model to test the hypothesis, which could mimic the clinical treatment and provide therapeutically relevant insights into the acute drug-induced stress response and regrowth. Unexpectedly, we found that the human endogenous retrovirus-like elements (HERVs) show an aberrant bursting in the adaptation. To further interrogate the adaptation, we did the longitudinal single-cell multi-omics sequencing. With a novel bioinformatic workflow, we integrated the HERV’s expression information with protein-coding genes profiling and chromatin accessibility. The preliminary result indicated that a subpopulation of HERV-high cells might transiently mediate the persistence of cancer cells at the early stage of the treatment, which coupled with whole transcriptomic and chromatin landscape reprogramming, and molecular subtype switching. In this study, we employed a new strategy to investigate the longitudinal adaptation route through treatment and uncover a non-canonical element, which shed new light on drug resistance research and novel target screening. Citation Format: Zijian Zhang, Yiyang Wang, Xinlong Luo, Xiaomei Zhan, Jun Ding, Tao P. Wu. Retrotransposable elements mediate the drug-tolerant persistence in claudin-low breast cancer chemo-treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5862.

Enhancing nitrogen removal efficiency for anammox granular sludge at low temperature by fulvic acids from different sources

The stable and efficient operation of the anaerobic ammonia oxidation (anammox) process in mainstream wastewater treatment at low temperatures still faces significant challenges. In this study, the effect of mineral fulvic acid (MFA) and biochemical fulvic acid (BFA) on the nitrogen removal efficiency of the anammox reactor at low temperature (20 °C) was investigated. The results demonstrated that both MFA and BFA could improve the nitrogen removal performance of the anammox reactor, with MFA exhibiting a more pronounced promotional effect than BFA. At concentrations of 30 mg total organic carbon (TOC)/L for both MFA and BFA, the nitrogen removal rate (NRR) increased by 26.68 % and 21.93 %, respectively. MFA and BFA stimulated the secretion of extracellular polymeric substances (EPS), preventing the disintegration of granular sludge at low temperatures, with a notable increase in the particle size of granular sludge, especially at high concentrations of MFA. Moreover, serving as electron shuttles, MFA demonstrated superior electron transfer ability compared to BFA, significantly enhancing the metabolic activity of anammox bacteria (AnAOB) under low temperatures. In addition, compared with BFA, MFA exhibited the potential to promote the growth of Candidatus_Kuenenia, offering a beneficial contribution to improving the nitrogen removal performance of the anammox reactor at low temperatures.

Algal-bacterial shortcut nitrogen removal model with seasonal light variations.

The algal-bacterial shortcut nitrogen removal (ABSNR) process can be used to treat high ammonia strength wastewaters without external aeration. However, prior algal-bacterial SNR studies have been conducted under fixed light/dark periods that were not representative of natural light conditions. In this study, laboratory-scale photo-sequencing batch reactors (PSBRs) were used to treat anaerobic digester sidestream under varying light intensities that mimicked summer and winter conditions in Tampa, FL, USA. A dynamic mathematical model was developed for the ABSNR process, which was calibrated and validated using data sets from the laboratory PSBRs. The model elucidated the dynamics of algal and bacterial biomass growth under natural illumination conditions as well as transformation processes for nitrogen species, oxygen, organic and inorganic carbon. A full-scale PSBR with a 1.2 m depth, a 6-day hydraulic retention time (HRT) and a 10-day solids retention time (SRT) was simulated for treatment of anaerobic digester sidestream. The full-scale PSBR could achieve >90% ammonia removal, significantly reducing the nitrogen load to the mainstream wastewater treatment plant (WWTP). The dynamic simulation showed that ABSNR process can help wastewater treatment facilities meet stringent nitrogen removal standards with low energy inputs.

Enhanced nitrogen removal via partial nitrification/denitrification coupled Anammox using three stage anoxic/oxic biofilm process with intermittent aeration

Pre-capturing organics in municipal wastewater for biogas production, combined with Anammox-based nitrogen removal process, improves the sustainability of sewage treatment. Thus, enhancing nitrogen removal via Anammox in mainstream wastewater treatment becomes very crucial. In present study, a three-stage anoxic/oxic (AO) biofilm process with intermittent aeration was designed to strengthen partial nitrification/denitrification coupling Anammox (PNA/PDA) in treatment of low C/N wastewater, which contained chemical oxygen demand (COD) of 79.8 mg/L and total inorganic nitrogen (TIN) of 58.9 mg/L. With a hydraulic retention time of 8.0 h, the process successfully reduced TIN to 10.6 mg/L, achieving a nitrogen removal efficiency of 83.3 %. The 1st anoxic zone accounted for 32.0 % TIN removal, with 10.3 % by denitrification and 21.7 % by PDA, meanwhile, the 2nd and 3rd anoxic zones contributed 19.4 % and 4.5 % of TIN removal, primarily achieved through PDA (including endogenous PD coupling Anammox). The 1st and 2nd intermittent zones accounted for 27.2 % and 17.0 % of TIN removal, respectively, with 13.7 %-21.3 % by PNA and 3.2 %-5.3 % by PDA. Although this process did not pursue nitrite accumulation in any zone (< 1.5 mg-N/L), PNA and PDA accounted for 35.1 % and 52.1 % of TIN removal, respectively. Only 0.21 % of removed TIN was released as nitrous oxide. The AnAOB of Candidatus Brocadia was enriched in each zone, with a relative abundance of 0.66 %-2.29 %. In intermittent zones, NOB had been partially suppressed (AOB/NOB = 0.73–0.88), mainly due to intermittent aeration and effective nitrite utilization by AnAOB since its population size was much greater than NOB. Present study indicated that the three-stage AO biofilm process with intermittent aeration could enhance nitrogen removal via PNA and PDA with a low N2O emission factor.

Meta-analysis of the clinical efficacy of the Gamma3 nail vs Gamma3U-blade system in the treatment of intertrochanteric fractures.

The traditional Gamma3 nail is a mainstream treatment for femoral intertrochanteric fractures. Literature reports that the Gamma3U-blade system can increase the stability of the Gamma3 nail and reduce complication incidence. However, comparative studies between the Gamma3U-blade and Gamma3 systems are limited; hence, this meta-analysis was performed to explore the clinical efficacy of these two surgical methods. To investigate the clinical efficacy of Gamma3 and Gamma3 U-blade for intertrochanteric fractures. A computerized search for Chinese and English literature published from 2010 to 2022 was conducted in PubMed, Cochrane, CNKI, Wanfang, and VIP databases. The search keywords were gamma 3, gamma 3 U blade, and intertrochanteric fracture. Additionally, literature tracking was performed on the references of published literature. The data were analyzed using Revman 5.3 software. Two individuals checked the inputs for accuracy. Continuous variables were described using mean difference and standard deviation, and outcome effect sizes were expressed using ratio OR and 95% confidence interval (CI). High heterogeneity was considered at (P < 0.05, I2 > 50%), moderate heterogeneity at I2 from 25% to 50%, and low heterogeneity at (P ≥ 0.05, I2 < 50%). Following a comprehensive literature search, review, and analysis, six articles were selected for inclusion in this study. This selection comprised five articles in English and one in Chinese, with publication years spanning from 2016 to 2022. The study with the largest sample size, conducted by Seungbae in 2021, included a total of 304 cases. Statistical analysis: A total of 1063 patients were included in this meta-analysis. The main outcome indicators were: Surgical time: The Gamma3U blade system had a longer surgical time compared to Gamma3 nails (P = 0.006, I2 = 76%). Tip-apex distance: No statistical significance or heterogeneity was observed (P = 0.65, I2 = 0%). Harris Hip score: No statistical significance was found, and low heterogeneity was detected (P = 0.26, I2 = 22%). Union time: No statistical significance was found, and high heterogeneity was detected (P = 0.05, I2 = 75%). Our study indicated that the Gamma3 system reduces operative time compared to the Gamma3 U-blade system in treating intertrochanteric fractures. Both surgical methods proved to be safe and effective for this patient group. These findings may offer valuable insights and guidance for future surgical protocols in hip fracture patients.

Achieving stable advanced nitrogen removal from mainstream municipal wastewater using integrated strategies in partial nitrification anammox (PNA) granular hybrid system

Partial nitrification anammox (PNA) is a promising technology for energy saving and nitrogen removal. The bottlenecks limiting the widespread application of PNA in mainstream municipal wastewater treatment include the difficulty in stably suppressing nitrite-oxidizing bacteria (NOB) and failure to meet discharge standards for total nitrogen (TN) due to high nitrate concentration in the effluent. To this end, this study aims to stably suppress NOB using integrated strategies (including the inoculated activated sludge pretreatment with FNA, low DO, residual ammonia nitrogen, and floc sludge discharge) while also investigating the feasibility and performance of coupling PNA with endogenous partial denitrification/anammox (EPDA) in a PNA granular hybrid system. During the 300 days of operation, the integrated strategies effectively stabilized the suppression of NOB, decreasing its abundance from 1.22 % to 0.55 %, and the final activity was reduced to 0.36 ± 0.12 mg-N/L/h. Meanwhile, the relative abundance of AnAOB as the dominant microbial community increased from 9.16 % to 24 %, with its activity reaching 2.84 ± 0.16 mg-N/L/h, limiting the supply of nitrite and ensuring the stable suppression of NOB. Typical cycle tests showed that EPDA and PNA were successfully coupled during the aeration stage with a nitrogen removal contribution rate of 80.55 %, ultimately achieving the average effluent TN and PO43--P were 4.22 mg/L and 0.09 mg/L, respectively. The metagenomic and metatranscriptomic sequencing results revealed that anammox bacteria (AnAOB) coexisted with ammonia-oxidizing bacteria (AOB), NOB, and endogenous denitrifying bacteria (EDB), and AnAOB played a primary role in the nitrogen removal process of mainstream PNA. This study brings mainstream PNA closer to widespread application and provides significant technical support for its engineering implementation.

Primary adipocytes as targetable drug depot to prevent post-surgical cancer recurrence

Surgery followed by adjuvant chemotherapy or radiation therapy remains the mainstream treatment for breast cancer in the clinic. However, cancer recurrence post surgery is still common. In view of the clinical practice that autologous fat tissue grafting is often used to facilitate breast reconstruction after lumpectomy, here we develop an in vivo targetable adipocyte-based drug depot for the prevention of post-surgical cancer recurrence. We show that primary adipocytes can be metabolically labeled with clickable chemical tags (e.g., azido groups), for subsequent conjugation of dibenzocyclooctyne (DBCO)-bearing cargo via efficient click chemistry. The conjugated cargo can retain well on the adipocyte membrane. By incorporating a cleavable linker between DBCO and cargo, the conjugated cargo can be gradually released from the surface of adipocytes to effect on neighboring cells. In the context of breast cancer surgery, azido-labeled adipocytes grafted to the surgical site can capture circulating DBCO-drugs for improved prevention of 4T1 triple-negative breast cancer (TNBC) recurrence and metastasis. This targetable and refillable adipocyte-based drug depot holds great promise for drug delivery, transplantation, and other applications.

Early Weight-bearing Rehabilitation Protocol After Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) injury is one of the common sports injuries. Anterior cruciate ligament reconstruction (ACLR) is the mainstream treatment for ACL injury, aiming to regain normal anatomical structure and stability of the knee joint and promote the patient's return to sports. Under the guidance of the concept of enhanced recovery after surgery, early weight-bearing rehabilitation (EWB) is an important factor affecting patient function and quality of life. However, there is no consensus on whether EWB rehabilitation can be performed after ACL surgery. This study aims to explore the safety and feasibility of EWB after ACL surgery. The study implemented a gradual EWB rehabilitation program in the experimental group, including weight-shifting training, balance training, and gait training on the affected lower limb, and assessed wound healing and stability of the knee joint. The study found that EWB after ACLR is safe and feasible. EWB rehabilitation not only does not pose a negative effect on the patient's knee pain, swelling, wound healing, and stability, but also helps to improve knee active flexion and quality of life faster and better. The EWB program in this study is simple, safe, and effective, and it provides strong theoretical guidance and practical demonstration for accelerated rehabilitation after ACLR.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Surgical outcomes after reoperation for patients with recurrent presacral tumors: a retrospective study

BackgroundRelevant reports on the surgical resection and prognosis of recurrent presacral tumors are limited. The objective of this study was to explore the outcomes associated with surgical resection of recurrent presacral tumors.MethodsThe data of patients with recurrent presacral tumors who received surgical resection in our hospital between June 2009 and November 2018 were retrospectively analyzed.ResultsThirty-one patients, comprising 22 females and 9 males, with recurrent presacral lesions were included in our study. A posterior approach was utilized in 27 patients, an anterior approach in 1 patient, and a combined approach in 3 patients. Intraoperative complications occurred in 13 patients (41.9%), while postoperative complications occurred in 6 patients (19.4%). The length of hospital stay was significantly shorter in patients who underwent the posterior approach compared to those who underwent the anterior and combined approaches (P = 0.002). The operative time for the posterior approach was significantly shorter compared to both the anterior and combined approaches (P = 0.006). Temporary tamponade was performed for hemostasis in 4 patients, while staged resection was performed in 2 patients during the surgical treatment process. After a median follow-up period of 115.5 months, 5 patients with recurrent malignant presacral tumors succumbed to tumor recurrence after reoperation in our hospital.ConclusionsSurgical resection remains the mainstream treatment for recurrent presacral tumors. The outcomes for recurrent benign presacral tumors after surgery demonstrate favorable results, whereas further enhancements are required to improve the outcomes for recurrent malignant presacral tumors after surgery.

Iron-electrolysis assisted anammox/denitrification system for intensified nitrate removal and phosphorus recovery in low-strength wastewater treatment

Two iron-electrolysis assisted anammox/denitrification (EAD) systems, including the suspended sludge reactor (ESR) and biofilm reactor (EMR) were constructed for mainstream wastewater treatment, achieving 84.51±4.38 % and 87.23±3.31 % of TN removal efficiencies, respectively. Sludge extracellular polymeric substances (EPS) analysis, cell apoptosis detection and microbial analysis demonstrated that the strengthened cell lysate/apoptosis and EPS production acted as supplemental carbon sources to provide new ecological niches for heterotrophic bacteria. Therefore, NO3−-N accumulated intrinsically during anammox reaction was reduced. The rising cell lysis and apoptosis in the ESR induced the decline of anammox and enzyme activities. In contrast, this inhibition was scavenged in EMR because of the more favorable environment and the significant increase in EPS. Moreover, ESR and EMR achieved efficient phosphorus removal (96.98±5.24 % and 96.98±4.35 %) due to the continued release of Fe2+ by the in-situ corrosion of iron anodes. The X-ray diffraction (XRD) indicated that vivianite was the dominant P recovery product in EAD systems. The anaerobic microenvironment and the abundant EPS in the biofilm system showed essential benefits in the mineralization of vivianite.

Empowering Pacific Patients on the Weight Loss Surgery Pathway: A Co-designed Evaluation Study

PurposeDespite having the highest medical needs by population for weight loss treatment, Pacific patients in Aotearoa New Zealand face substantial levels of attrition in publicly funded weight loss surgery programs. In collaboration with the Auckland City Hospital bariatric surgery team, a Pacific-led preoperative weight loss surgery program was co-designed, delivered, and evaluated between 2020 and 2023.Materials and MethodsThis was a single-arm, prospective co-designed evaluation study that took place at Auckland City Hospital in Aotearoa New Zealand. Participants were Pacific patients (n = 14) referred to the weight loss surgery program. Survey and video diaries were analyzed to determine if the program had the potential to increase Pacific patient retention through the preoperative stage of weight loss surgery, increase surgery completion rates, and improve the quality of treatment experiences.ResultsNine out of 14 participants attended all preoperative sessions. Six participants subsequently underwent weight loss surgery. Program components that had positive impacts on patient success and satisfaction were accessibility, information quality, having Pacific role models, cultural safety, and the group support system. The patients found the program to be culturally anchored and there was support for the implementation of the program going forward.ConclusionThis study demonstrated how a culturally anchored intervention can increase patient retention for those patients who may not respond to mainstream treatment. Adjusting existing preoperative weight loss surgery programs to integrate Pacific-led models of healthcare has the potential to increase Pacific patient resiliency to follow through with surgery.Graphical

Towards the co-benefits of carbon capture, utilization and sequestration: A life cycle assessment study for steel slag disposal

Achieving decarbonization in the steel industry is of paramount importance for global carbon neutrality. Given the unavoidable generation of calcium-containing steel slag and carbon-rich flue gas emissions in the steelmaking process, steel slag carbonation is considered a CCUS technology capable of achieving pollution and carbon reduction in the steel industry. This study conducts a life cycle assessment (LCA) of the environmental impacts generated within the system boundaries of mainstream hot braising steel slag treatment and a novel carbonation steel slag approach. Results of the research demonstrate that the carbonation route based on carbon capture, utilization, and storage (CCUS) technology reduces the global warming potential (GWP) by 480% compared to the mainstream hot braising route, yielding −76.78 kg CO2 eq./t steel slag. The carbonation route also mitigates the environmental impact of pollutant emissions; however, it introduces a burden shifting associated with energy and resource consumption. Furthermore, to tackle the challenges of industrial application of steel slag carbonation, this study has explored upgrading schemes and proposed a future carbonation steel slag route that achieves process upgrades. By enabling carbonation of flue gas and improving carbonation efficiency, this route is forecasted to elevate the potential of carbon footprint reduction from 5% to 15% throughout the entire life cycle of steelmaking process. The study confirms that steel slag carbonation is a viable carbon-negative technology, delivering a substantiated CCUS solution for achieving co-benefits of pollution and carbon reduction in the steel industry.

Comammox and unknown ammonia oxidizers contribute to nitrite accumulation in an integrated A-B stage process that incorporates side-stream EBPR (S2EBPR)

A novel integrated pilot-scale A-stage high rate activated sludge, B-stage short-cut biological nitrogen removal and side-stream enhanced biological phosphorus removal (A/B-shortcut N-S2EBPR) process for treating municipal wastewater was demonstrated with the aim to achieve simultaneous and carbon- and energy-efficient N and P removal. In this studied period, an average of 7.62 ± 2.17 mg-N/L nitrite accumulation was achieved through atypical partial nitrification without canonical known NOB out-selection. Network analysis confirms the central hub of microbial community as Nitrospira, which was one to two orders of magnitude higher than canonical aerobic oxidizing bacteria (AOB) in a B-stage nitrification tank. The contribution of comammox Nitrospira as AOB was evidenced by the increased amoB/nxr ratio and higher ammonia oxidation activity. Furthermore, oligotyping analysis of Nitrospira revealed two dominant sub-clusters (microdiveristy) within the Nitrospira. The relative abundance of oligotype II, which is phylogenetically close to Nitrospira_midas_s_31566, exhibited a positive correlation with nitrite accumulation in the same operational period, suggesting its role as comammox Nitrospira. Additionally, the phylogenetic investigation suggested that heterotrophic organisms from the family Comamonadacea and the order Rhodocyclaceae embedding ammonia monooxygenase and hydroxylamine oxidase may function as heterotrophic nitrifiers. This is the first study that elucidated the impact of integrating the S2EBPR on nitrifying populations with implications on short-cut N removal. The unique conditions in the side-stream reactor, such as low ORP, favorable VFA concentrations and composition, seemed to exert different selective forces on nitrifying populations from those in conventional biological nutrient removal processes. The results provide new insights for integrating EBPR with short-cut N removal process for mainstream wastewater treatment.

How to Manage Advanced Differentiated Thyroid Cancer: Step-by-Step Analysis from Two Italian Tertiary Referral Centers

Background: Differentiated thyroid carcinoma (DTC) has an excellent prognosis; however, advanced disease is associated with a worse prognosis and is relatively common. Surgery followed by RAI treatment remains the mainstream treatment for a large majority of patients with high- and intermediate-risk DTC, but its benefits should be carefully weighed against the potential for harm. The aim of this paper is to critically review the experience in treating advanced DTC at two tertiary referral centers in Italy. Methods: Retrospective analysis of 300 patients who underwent surgery for ADTC over 30 years. Results: The complication rate was 50.33%. A total of 135 patients (45%) remained at regular follow-up, 118 (87.4%) were alive, while 17 (12.6%) were deceased. The mean overall survival at 12 years was 84.8% with a mean of 238 months. Eleven patients (8.1%) experienced a relapse after a median of 13 months. Conclusions: ADTC patients adequately treated can achieve prolonged survival even in the case of metastasis or disease relapse. Patients with ADTC should be referred to high-volume centers with the availability of an extended multidisciplinary team to receive tailored treatment.

Functional differentiation of size-fractionated biomass in the mixotrophic mainstream UASB-anammox process

The soluble organic matter in sewage is one of the major obstacles to the stable operation of mainstream anammox, which would induce the excessive proliferation of heterotrophic bacteria. Given its excellent volumetric nitrogen removal rate (>2.0 kg N m−3 d−1) in mainstream treatment at 15 °C, the physicochemical properties and microbial ecology of size-fractionated aggregates in mixotrophic anammox-UASB system were investigated to develop strategies for population management. The presence of glucose or acetate (COD/N = 1.0) decreased the contribution of anammox by approximately 30 %, thereby causing the increase of effluent TN concentrations to over 12 mg N L−1, in which NH4+-N accounted for ∼85 %. Interestingly, the relative abundance of anammox bacteria were increased from 1.0 % in flocs (<0.2 mm) to 34.9 % in big granules (>0.8 mm) of the acetate-fed reactor, while the abundance of denitrifying bacteria was decreased from 74.0 % in flocs to 12.0 % in big granules. Similar trend was also observed for the glucose-fed reactor. As a result, the expressions of anammox functional genes, specific anammox activity, extracellular polymeric substances and heme c contents were all increased with the increase of particle sizes. Notably, in contrast to the glucose-fed biomass, the acetate-fed biomass showed significant potential of denitratation. Accordingly, the screen with a size of around 0.2 mm may be an effective tool to uncouple the retention times of denitrifying bacteria and anammox bacteria. These results provided direct evidences for functional differentiation of size-fractionated biomass and would guide us to balance their functions for a satisfactory effluent quality.

Tumor-Microenvironment-Activatable Nanoparticle Mediating Immunogene Therapy and M2 Macrophage-Targeted Inhibitor for Synergistic Cancer Immunotherapy.

Immunotherapy has achieved prominent clinical efficacy in combating cancer and has recently become a mainstream treatment strategy. However, achieving broad efficacy with a single modality is challenging, and the heterogeneity of the tumor microenvironment (TME) restricts the accuracy and effectiveness of immunotherapy strategies for tumors. Herein, a TME-responsive targeted nanoparticle to enhance antitumor immunity and reverse immune escape by codelivering interleukin-12 (IL-12) expressing gene and colony-stimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (PLX) is presented. The introduction of disulfide bonds and cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) peptides conferred reduction reactivity and tumor targeting to the nanoparticles, respectively. It is hypothesized that activating host immunity by the local expression of IL-12, while modulating the tumor-associated macrophages (TAM) function through blocking CSF-1/CSF-1R signaling, could constitute a feasible approach for cancer immunotherapy. The fabricated functional nanoparticle successfully ameliorated the TME by stimulating the proliferation and activation of T lymphocytes, promoting the repolarization of TAMs, reducing myeloid-derived suppressor cells (MDSCs), and promoting the maturation of dendritic cells (DC) as well as the secretion of antitumor cytokines, which efficiently suppressed tumor growth and metastasis. Finally, substantial changes in the TME were deciphered by single-cell analysis including infiltration of different cells, transcriptional states, secretory signaling and cell-cell communications. These findings provide a promising combinatorial immunotherapy strategy through immunomodulatory nanoparticles.