Treatment Cycles Research Articles

Abstract 2505: Immune dynamics and response predictors to regorafenib, ipilimumab, and nivolumab (RIN) treatment in chemotherapy resistant microsatellite stable (MSS) metastatic colorectal cancer (mCRC)

Abstract Background: In our previous study, RIN therapy in MSS mCRC patients, excluding those with liver metastases, yielded a notable 36.4% objective response rate. RIN treatment was observed to remodel the local tumor microenvironment by enhancing immune infiltration, especially in responders. Systemic immunity, as assessed through peripheral blood analysis, showed that responders had lower baseline immune activity, which increased markedly post-treatment. Patients with liver metastases demonstrated a reduced CD4/CD8 T cell ratio, indicative of immunosenescence. Methods: Building on our prior research, we analyzed blood samples from 29 chemotherapy-resistant MSS mCRC patients undergoing RIN therapy, collected at baseline and after two consecutive treatment cycles. Two 28-marker spectral flow cytometry panels were used to assess immune senescence and cytokine production in lymphocytes. Additionally, T cell receptor repertoires and transcriptional profiles were analyzed using RNA sequencing from sorted non-naïve T cells. Results: The study unveiled distinct immunological profiles in MSS mCRC patient responders vs non-responders to RIN treatment. Responders demonstrated increased numbers of newly expanding CD8 T cell clones on-treatment, indicative of an active immune responses. In contrast, non-responders displayed evidence of increased DNA damage in circulating lymphocytes (T, B, and NK cells), as marked by elevated γ-H2AX levels. We also identified divergent cytokine production profiles patterns at baseline: T cells in non-responders demonstrated increased capacity for production of IL-2, IL-10, IL-4/-13, and IL-22, while production of IFN-γ in both T cells and NK cells correlated with improved outcomes. Notably, patients with liver metastases exhibited greater frequencies of senescent T cells, characterized by increased expression of senescence markers (SA-βGal, CD57, Granzyme B/K) and a reduction in CD27 and CD28 in CD4 T cells, along with an accumulation of terminally differentiated CD8 T cells both pre- and post-treatment. Additionally, RNA sequencing revealed an upregulation of FOXO1 related genes in non-naive T cells of responder patients, which is consistent with its important role for this pathway in attenuating senescence and maintenance of stem-like properties in T cells. Conclusions: The effectiveness of RIN therapy is associated with baseline functional potential of circulating T cells and an on-treatment expansion of T cell clonotypes. Pre-existing and persistent features of senescence and DNA damage in circulating lymphocytes may be a major barrier to RIN treatment efficacy in MSS colorectal cancer and should be validated further in future studies. Citation Format: Jian Ye, Chongkai Wang, Colt Egelston, Weihua Guo, Peter Lee, Marwan Fakih. Immune dynamics and response predictors to regorafenib, ipilimumab, and nivolumab (RIN) treatment in chemotherapy resistant microsatellite stable (MSS) metastatic colorectal cancer (mCRC) [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 2505.

Abstract 23: The use of baboon envelope pseudotyped lentiviral (BaLV) vector allows high-efficiency transduction of CD8+ T cells

Abstract CAR-T (chimeric antigen receptors T) cell therapy has been proven to be effective in treating various types of cancers. To prevent graft vs. host disease, CAR-T cells are mostly produced from the patient’s own T-cells and transduced using pseudotyped vesicular stomatitis virus glycoprotein (VSV-G) lentivirus system. Typically, CD8+ effector T cells have relatively low transduction rates, compared with CD4+ T cells, and yet it is the CD8+ T cells that are the dominant effector immune cells in a CAR product. To achieve high efficacy of the CAR-positive effector T cells, a higher number of the patient’s CD8+ T cells are needed for transduction. However, cancer patients may not have enough T cells by the time they are eligible for CAR-T therapy due to multiple treatment cycles. One potential way to overcome this problem is to achieve a much higher transduction rate of the CD8+ T cells. Recently, our lab published the use of pseudotyping CAR lentivirus with baboon endogenous retroviral envelope (BaEV) for the generation of CAR transduced natural killer (NK) cells, exhibiting high transduction rates of above 50%. BaEV lentivirus targets the amino acid transporter, SLC1A5 (ASCT2), to enter the cell. SLC1A5 is highly expressed on activated NK and T cells. Therefore, we hypothesized that CAR-T transduced with BaEV lentivirus will have increased transduction rates compared with VSV-G. To assess transduction, we used anti-mesothelin (MSLN) CAR construct which consists of the mesothelin single chain variable fragment (scFv), CD8α hinge and transmembrane domain, 4-1BB costimulatory domain, and a CD3ζ activation domain, followed with GFP linked by self-cleavage P2A. The concentrated virus was titrated in Jurkat cells, resulting in 90% transduction efficiency with VSV-G and 50% with BaEV, for the same amount of virus. Primary CD8+ T cells were isolated from the peripheral blood of 3 healthy donors and activated with CD3/CD28 beads for three days prior to transduction. Then, the cells were transduced with either VSV-G or BaEV meso-CAR pseudotyped lentiviruses. Transduction rates were measured by flow cytometry, 3 days post-transduction. In addition, the CAR-T cells were expanded in vitro to evaluate their cytotoxicity against the mesothelin-positive cell line OVCAR-8, for 24 hours. VSV-G led to 10-20% transduction rates, while BaEV exhibited much higher transduction rates (55-70%), leading to improved cytotoxicity against the tumor cells. The successful increase of transduction rates for CD8+ CAR-T using our BaEV lentiviral system can be utilized in the clinic to treat patients that previously didn’t qualify for adoptive therapy, due to low lymphocyte counts. In addition, higher numbers of CD8+ CAR-T cells may result in better tumor control in both blood and solid tumor settings, compared with the traditional approach for CAR-T production. Citation Format: Isabel Kaplan, Michal Sheffer, Yasmin Abdulhamid, Eden Bobilev, Rizwan Romee. The use of baboon envelope pseudotyped lentiviral (BaLV) vector allows high-efficiency transduction of CD8+ T cells [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 23.

Two cases of severe oral mucositis caused by atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma.

Atezolizumab is an immune checkpoint inhibitor specific for the programmed death-1 (PD-1) receptor. In this case report, we describe two cases of oral mucositis that developed following the initiation of a systemic chemotherapy regimen comprising atezolizumab and bevacizumab for recurrent hepatocellular carcinoma. After 2 or 3 cycles of treatment, each patient presented with mucosal ulcers in the mouth, oral pain, difficulty in speech and oral intake, and both were admitted to our hospital for management. Following rule out of other conditions such as pharyngeal ulcers, herpetic mucositis, denture or oral trauma, or necrotizing mucositis, both patients were diagnosed with oral mucositis as a severe immune-related adverse event. Oral candidiasis was observed in both cases and should be considered a risk factor for the development of oral mucositis. Chemotherapy was discontinued and treatment with prednisolone was started, along with supportive care. The oral mucositis improved, and prednisolone was gradually reduced; however, in one patient, discontinuation of chemotherapy led to a recurrence of hepatocellular carcinoma. The other patient was lost to follow-up. In patients with risk factors, attention must be paid to the development of oral mucositis during immune checkpoint inhibitor treatment.

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells.

Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells. Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot. Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability per se, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment. The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.

The Application of an Upflow Anaerobic Sludge Blanket Reactor in the Treatment of Brewery and Dairy Wastewater: A Critical Review

Brewery (BW) and dairy (DW) wastewater are two types of agro-industrial wastewater that are generated in large amounts and, therefore, should be treated effectively and in an environmentally beneficial manner. Both these wastewater types are characterized by a high COD, BOD5, and nutrient content, and conventional wastewater treatment methods such as an activated sludge process may prove to be inefficient due to the possibility of foaming, large biomass production, low activity at low temperatures, and risk of overloading the reactor with a load of organic pollutants. In the context of the described difficulties, anaerobic processes seem to be the best alternative. An interesting research area is the co-digestion of these wastewaters. However, this research direction, so far, has not been frequently reported. Given the gap in the current knowledge, this literature review aims to assess the possibility of BW and DW digestion in anaerobic reactors and provide up-to-date data on the post-treatment methods of effluent generated after the anaerobic digestion process. Despite numerous advantages, anaerobic treatment often requires post-effluent treatment to complete the treatment cycle.

Prognostic value of tumor markers ProGRP, NSE and CYFRA 21-1 in patients with small cell lung cancer and chemotherapy-induced remission.

Despite successful response to first line therapy, patients with small-cell lung cancer (SCLC) often suffer from early relapses and disease progression. To investigate the relevance of serum tumor markers for estimation of prognosis at several time points during the course of disease. In a prospective, single-center study, serial assessments of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1) and carcino-embryogenic antigen (CEA) were performed during and after chemotherapy in 232 SCLC patients, and correlated with therapy response and overall survival (OS). ProGRP, NSE and CYFRA 21-1 levels decreased quickly after the first chemotherapy cycle and correlated well with the radiological response. Either as single markers or in combination they provided valuable prognostic information regarding OS at all timepoints investigated: prior to first-line therapy, after two treatment cycles in patients with successful response to first-line therapy, and prior to the start of second-line therapy. Furthermore, they were useful for continuous monitoring during and after therapy and often indicated progressive disease several months ahead of radiological changes. The results indicate the great potential of ProGRP, NSE and CYFRA 21-1 for estimating prognosis and monitoring of SCLC patients throughout the course of the disease.

Efficacy of Oral Prednisolone in the Management of Idiopathic Granulomatous Mastitis

Background: Idiopathic granulomatous mastitis (IGM) is a benign inflammatory lesion of the mammary gland. Globally it possesses a major diagnostic and therapeutic problem. To date, there is no universally agreed treatment for this condition. Many treatment modalities have been attempted from conservative therapy to mastectomy but none of them has shown satisfactory results. Recent studies have shown promising results of corticosteroids on idiopathic granulomatous mastitis, so steroid therapy can be an effective treatment for idiopathic granulomatous mastitis. The goal of the study is to provide a therapeutic strategy in the future for idiopathic granulomatous mastitis. Methods: Our study included all patients with idiopathic granulomatous mastitis confirmed histologically by core needle/incisional biopsy at the general surgery unit of Chittagong Medical College Hospital and the private hospitals in the Chittagong Metropolitan City for a period of one year from October 2016 to September 2017. A total of seventy patients were included in the study provided they fulfilled predetermined criteria. All of them were included in this study by purposive sampling. After diagnosis oral prednisolone (1mg/kg/day) was given and the cases were observed by personal interview and through telephone interview. The patients were on follow-up for 06 months. Age, size of the breast lump, breast pain, nipple discharge, and skin changes were recorded in all cases. Results were analyzed using mean, percentage, and proportion as appropriate. Results: The mean age was 26.35±13.5 years ranging from 19 to 40 years. Out of 70 patients, Core cut biopsy was done in 55 patients (78.58%), and incisional biopsy with abscess drainage was performed in 15 patients (21.42%). 59 patients (84.28%) had complete recovery after a single cycle of steroid treatment, remaining 11 patients (15.72%) had recurrence, among them 6 patients were cured after 2nd cycle of steroids but unfortunately, 5 patients did not respond. Though complications were found in 50 patients, all of them made good progress in the short term. Conclusion: We recommend steroid therapy as the first-line treatment in our study. However, prospective, randomized clinical trials are needed to determine the treatment algorithm. Mediscope 2024;11(1): 22-26

The impact of thyroid autoimmunity on pregnancy outcomes in women with unexplained infertility undergoing intrauterine insemination: a retrospective single-center cohort study and meta-analysis.

Infertility affects 8-12% of couples worldwide, with 15-30% classified as unexplained infertility (UI). Thyroid autoimmunity (TAI), the most common autoimmune disorder in women of reproductive age, may impact fertility and pregnancy outcomes. However, the underlying mechanism is unclear. This study focuses on intrauterine insemination (IUI) and its potential association with TAI in UI patients. It is the first meta-analysis following a comprehensive literature review to improve result accuracy and reliability. Retrospective cohort study analyzing 225 women with unexplained infertility, encompassing 542 cycles of IUI treatment. Participants were categorized into TAI+ group (N=47, N= 120 cycles) and TAI- group (N=178, N= 422 cycles). Additionally, a systematic review and meta-analyses following PRISMA guidelines were conducted, incorporating this study and two others up to June 2023, totaling 3428 IUI cycles. Analysis revealed no significant difference in independent variables affecting reproductive outcomes. However, comparison based on TAI status showed significantly lower clinical pregnancy rates (OR: 0.43, P= 0.028, 95%CI: 0.20-0.93) and live birth rate (OR: 0.20, P= 0.014, 95%CI: 0.05 ~ 0.71) were significantly lower than TAI- group. There was no significant difference in pregnancy rate between the two groups (OR: 0.61, P= 0.135, 95%CI: 0.32-1.17). However, the meta-analysis combining these findings across studies did not show statistically significant differences in clinical pregnancy rates (OR:0.77, P=0.18, 95%CI: 0.53-1.13) or live birth rates (OR: 0.68, P=0.64, 95%CI: 0.13-3.47) between the TAI+ and TAI- groups. Our retrospective cohort study found an association between TAI and reduced reproductive outcomes in women undergoing IUI for unexplained infertility. However, the meta-analysis incorporating other studies did not yield statistically significant associations. Caution is required in interpreting the relationship between thyroid autoimmunity and reproductive outcomes. Future studies should consider a broader population and a more rigorous study design to validate these findings. Clinicians dealing with women with unexplained infertility and TAI should be aware of the complexity of this field and the limitations of available evidence.

Efficient removal of E. coli from wastewater by novel phytofabricated nano-zinc using antibacterial potential, kinetic studies, and response surface methodology

The present investigation explores the antibacterial potential of novel ZnO-NPs synthesized from Acacia nilotica pods extract and immobilized onto sodium alginate beads to control bacterial pollution in wastewater. Phenolics and flavonoids were major phytoconstituents acting as capping, reducing, and stabilizing agents. UV–Vis analysis showed strong absorption band at 340 nm. XRD and TEM revealed hexagonal crystalline structure for zincite of average particles diameter 33.87 and 32.74 nm, respectively. FTIR demonstrated several bands with functional groups (O–H, C-H, C = O, C = C, and C–O–C) involved in ZnO-NPs synthesis. SEM images showed NPs surface completely colonized by E.coli, while EDX spectrum showed signals for zinc (52.94%) and oxygen (26.58%) confirming NPs purity. Adhesion capacity studies revealed ZnO-NPs potential (0.5 g) to remove E.coli after 120 min. Kinetic and isotherm studies indicated that pseudo-second-order model and Freundlich isotherm were best fit describing adhesion mechanism. Electrostatic attraction between negatively charged E.coli and positively charged ZnO-NPs was followed by generation of H2O2 leading to cell apoptosis. Adhesion optimization using Box–Behnken design under response surface methodology was 99.8% at disinfectant dose 30 g/L, contact time 6 h, and E.coli concentration 150 × 107 cfu/mL. For application, real wastewater was treated with removal 98.2%, 97.2%, and 96.5% for total coliform, fecal coliform, and E.coli, respectively, after 6 h. ZnO-NPs showed sustainable efficiency during four consecutive cycles of treatment. The study concluded the efficiency, eco-friendly and cost-effectiveness of phytofabricated ZnO-NPs as disinfectants for wastewater and recommended future studies on large scale for possible wastewater reuse in safe unrestricted irrigation.

Safety and efficacy of atezolizumab plus bevacizumab combination therapy in patients with unresectable hepatocellular carcinoma undergoing dialysis: a case series.

Three patients aged 79, 75, and 81years with unresectable hepatocellular carcinoma (HCC) and undergoing maintenance hemodialysis were treated with a combination of atezolizumab and bevacizumab. The patients, respectively, received their 22nd, 2nd, and 4th treatment cycles, and one achieved long-term stable disease. No serious adverse events, including immune-related adverse events, were observed in any patient. Remarkable progress has been made in chemotherapy for cancer; however, the efficacy and safety of chemotherapy in patients undergoing hemodialysis have not been adequately elucidated. This report provides novel insights into the feasibility and outcomes of atezolizumab and bevacizumab combination therapy in patients with HCC undergoing hemodialysis, highlighting its potential as a viable treatment option with manageable side effects.

The isomorphous substitution of Si(4Al) with P in FAU zeolite and its stabilization effect

It's a dream to make zeolites more stable so as to keep the activity and stability of the catalyst. Phosphorus modification is an effective method, however, the known post-modification predominantly presents as non-framework P, and the P-loss is a big trouble in application. We have discovered that in the reaction of PCl3 or SiCl4 + PCl3 with NaY zeolite, a portion of P enters the framework of the zeolite, forming a PO4-AlO4 structure. Further investigations revealed that P cannot be incorporated into the framework through P for Al isomorphous substitution, but rather through isomorphous substitution with Si(4Al). PCl3 exhibits two effects in reaction: at lower quantities, it mainly undergoes isomorphous substitution with Si(4Al); at higher quantities, it leads to zeolite dealumination generating aluminum vacancies, which disrupt the zeolite framework or promotes Si for Al isomorphous substitution. After hydrothermal aging at 800 °C for 4 h, the stable presence of framework PO4-AlO4 implies that the weakest site Si(4Al) becomes the more stable site P(4Al) in the Y zeolite framework. Compared with the JPY (prepared by impregnating (NH4)2HPO4 solution to high silica Y zeolite) sample, after 10 cycles of hydrothermal and water washing treatment, the P2O5 loss rate of DPY (prepared by SiCl4 + PCl3 with NaY) zeolite ranged from 0.4 % to 3.5 %, significantly lower compared to the range of 18.7 % to 25.9 % observed in the JPY sample. This indicates that in DPY zeolite, the interaction between P and the zeolite is stronger and less prone to loss. Moreover, P is more uniformly distributed on the surface and bulk phase of DPY than JPY sample.

A virtuous cycle for thermal treatment of polyvinyl chloride and fermentation of lignocellulosic biomass

In this study, a highly corrosive substance, hydrogen chloride (HCl), obtained through the dechlorination of polyvinyl chloride (PVC), was utilized for acid pretreatment in the production of lignocellulosic bioethanol. The study determined that the optimal concentration of HCl was 5 wt%, resulting in the highest sugar recovery of 85.98% from oak sawdust when treated at 130 °C for 2 h. The production of bioethanol (BE) by Pichia stipitis using the hydrolysates treated with 5% HCl and enzymes, supplemented with N-sources, demonstrated efficient productivity compared to the control group. To achieve a virtuous cycle, two residues from the dechlorination of PVC and saccharification of oak sawdust were pyrolyzed in a carbon dioxide (CO2) environment. The generation of carbon monoxide (CO) was significantly enhanced by the homogeneous reaction between CO2 and volatiles. This homogeneous reaction led to the modification of the compositional matrix in the oil. The generation of low-molecular-weight hydrocarbons in oil was observed under CO2 conditions. To impart high reactivity to CO2, the catalytic pyrolysis of the residues was performed in the presence of Ni/SiO2. Indeed, the CO2 reactivity was catalytically enhanced, which greatly expedited the redox kinetics underlying the chemical reactions of CO2 with volatiles from PVC. The experimental findings provide a great avenue for hybridizing the thermochemical process of PVC and the biological bioethanol production process of lignocellulosic biomass. Such efforts are promising from the perspective of economic viability in the waste-to-energy and biofuel fields.

Time-Lapse Incubation for Embryo Culture-Morphokinetics and Environmental Stability May Not Be Enough: Results from a Pilot Randomized Controlled Trial.

Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016-2020. In total, 102 patients were randomized into three groups: (1) conventional incubation with morphological evaluation only (n = 34), (2) TLI with both morphological and morphokinetic evaluations (n = 32), and (3) TLI with morphological evaluation only (n = 36). All arms were cultured in ESCO-MIRI® incubators. A total of 1061 injected mature oocytes were evaluated (420 in arm 1, 285 in arm 2, and 356 in arm 3). The primary outcome was live birth rates. Secondary outcomes included clinical and cumulative pregnancy rates as well as embryo quality. Embryos in arm 3 were retrospectively evaluated for their morphokinetic score. Results: No significant difference was found in the live birth rate for single embryo transfer cycles (SET) (35% vs. 31.6% vs. 24%, p = 0.708) or double embryo transfer (DET) cycles (41.7% vs. 38.5% vs. 36.4%, p = 0.966). Comparable pregnancy rates, clinical pregnancy rates, and cumulative pregnancy were found for similar top-quality embryos for days 2, 3, and blastocyst stages across groups. A similar number of embryos were suitable for either transfer or cryopreservation within the different groups. For 62.8% of the embryos in arm 3, the morphokinetic and morphologic evaluations were similar. In only 2/36 (5.6%) treatment cycles, the use of morphokinetic scoring may have helped the patient avoid undergoing an additional treatment cycle. In the other cases, morphokinetic scoring would not have changed the end point of pregnancy. Conclusions: The two components of the TLI system-undisturbed culturing and morphokinetic embryo grading-do not appear to have a significant additional value in reproductive outcome, although these results should be validated by an RCT.

Immobilization of Horseradish Peroxidase and Myoglobin Using Sodium Alginate for Treating Organic Pollutants

Removing organic pollutants from wastewater is crucial to prevent environmental contamination and protect human health. Immobilized enzymes are increasingly being explored for wastewater treatment due to their specific catalytic activities, reusability, and stability under various environmental conditions. Peroxidases, such as horseradish peroxidase (HRP) and myoglobin (Mb), are promising candidates for immobilized enzymes utilized in wastewater treatment due to their ability to facilitate the oxidation process of a wide range of organic molecules. However, the properties of the carrier and support materials greatly influence the stability and activity of immobilized HRP and Mb. In this research, we developed immobilized HRP and Mb using support material composed of sodium alginate and CaCl2 as carriers and glutaraldehyde as a crosslinking agent. Following this, the efficacy of immobilized HRP and Mb in removing aniline, phenol, and p-nitrophenol was assessed. Both immobilized enzymes removed all three organic pollutants from an aqueous solution, but Mb was more effective than HRP. After being immobilized, both enzymes became more resilient to changes in temperature and pH. Both immobilized enzymes retained their ability to eliminate organic pollutants through eight treatment cycles. Our study uncovered novel immobilized enzyme microspheres and demonstrated their successful application in wastewater treatment, paving the way for future research.

Gα12 and endoplasmic reticulum stress-mediated pyroptosis in a single cycle of dextran sulfate-induced mouse colitis

Inflammatory bowel disease (IBD) pathogenesis involves complex inflammatory events and cell death. Although IBD involves mainly necrosis in the digestive tract, pyroptosis has also been recognized. Nonetheless, the underlying basis is elusive. Gα12/13 overexpression may affect endoplasmic reticulum (ER) stress. This study examined how Gα12/13 and ER stress affect pyroptosis using dextran sulfate sodium (DSS)-induced colitis models. Gα12/13 levels were increased in the distal and proximal colons of mice exposed to a single cycle of DSS, as accompanied by increases of IRE1α, ATF6, and p-PERK. Moreover, Il-6, Il-1β, Ym1, and Arg1 mRNA levels were increased with caspase-1 and IL-1β activation, supportive of pyroptosis. In the distal colon, RIPK1/3 levels were enhanced to a greater degree, confirming necroptosis. By contrast, the mice subjected to three cycles of DSS treatments showed decreases of Gα12/13, as accompanied by IRE1α and ATF6 suppression, but increases of RIPK1/3 and c-Cas3. AZ2 treatment, which inhibited Gα12, has an anti-pyroptotic effect against a single cycle of colitis. These results show that a single cycle of DSS-induced colitis may cause ER stress-induced pyroptosis as mediated by Gα12 overexpression in addition to necroptosis, but three cycles model induces only necroptosis, and that AZ2 may have an anti-pyroptotic effect.

Enhanced photocatalytic activity of FeSO4 in a ZnO photocatalyst with H2O2 for dye degradation

In this study, the photocatalytic degradation efficiency of ZnO synthesized by a hydrothermal method and iron-supported ZnO catalysts by an impregnation method, dried (D) and calcined (C), was evaluated, through the degradation of methylene blue (MB) and methyl orange (MO) molecules under UV irradiation. The catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption-desorption, and UVvisible diffuse reflectance spectroscopy (DRS). XRD showed that FeSO4 is supported on ZnO, and the XPS study revealed higher concentrations of hydroxyl groups and Fe3+ for the dried catalyst. The bandgap energies were 3.24, 3.23, and 3.19 eV for ZnO, Fe/ZnO D and Fe/ZnO C, respectively. The results revealed that Fe/ZnO D with H2O2 exhibited a higher photocatalytic degradation efficiency than ZnO, achieving 97% and 99% degradation for MB and MO at 10 min, which implies that the integrated iron in ZnO serves as an electron-hole separator. In addition, the catalyst has a larger BET specific area, the presence of hydroxyl groups and sulfate ions on the surface of the catalyst with holes forms hydroxyl radicals (•OH), and the presence of Fe3+ on the surface catalyst with H2O2 produces more •OH radicals. •OH radicals are the major oxidation species in this process, which promotes the degradation of dyes. The photocatalytic dye degradation efficiency was also evaluated for various catalyst doses, dye concentrations and solution pH values. Moreover, the stability of the catalyst over repeated cycles of dye treatment was demonstrated.

Desalination and nutrient removal from tertiary treated urban wastewater by a radial capacitive deionizer

This study focused on removing salts and nutrients (nitrogen and phosphorus) from tertiary treated urban wastewater by capacitive deionization. The performance of a pilot-scale radial capacitive deionizer subjected to varying feed flow rates during the purification stage and constant flow rates during the reject stage was evaluated. This operational strategy aimed to maximize the water recovery rates of the system, with electrical adjustments being made proportionally to the water recovery rate. Lower hydraulic loads resulted in the radial capacitive deionizer removing more ions from the sewage, albeit with higher specific energy consumption. Optimal operational conditions reduced conductivity by 92.8 %, with a specific energy consumption of 2.17 kWhm−3. Significant removals of ammonium, nitrite, nitrate, and orthophosphate ions were observed, with average specie reductions of up to 84, 91.4, 100, and 60.5 %, respectively. Higher rates of treated water recovery resulted in lower ion removal reduction and energy consumption. The limiting step of the process referred to ion desorption, requiring the correct adjustment of the time lapse, flow rate, and applied electrical voltage to ensure the efficiency of the subsequent purification stage. A loss of efficiency was observed when the process was run continuously, thus emphasizing the strategic significance of capacitor rinsing during the rejection phase across multiple subsequent treatment cycles.

Disease control in patients with non-small cell lung cancer using pemetrexed: Investigating the best treatment strategy.

Pemetrexed (PEM) is the primary chemotherapy for non-small cell lung cancer (NSCLC), showing potential for long-term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor-1 (TTF-1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001). Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF-1 positivity, could enhance disease control rates and extend survival.

Using resampled nSight-2 hyperspectral data and various machine learning classifiers for discriminating wetland plant species in a Ramsar Wetland site, South Africa

Mapping wetland ecosystems at the species level provides critical information for understanding the nutrient cycle, carbon sequestration, retention and purification of water, waste treatment and pollution control. However, wetland ecosystems are threatened by climate variability and change and anthropogenic activities; thus, their assessment and monitoring have become critical to inform proper management interventions. Contemporary studies show that satellite-based Earth observation (EO) has significant potential for achieving this task. While many multispectral EO data are freely and readily available, its broad spectral bands limit its utility in differentiating subtle differences among similar plant species. In contrast, hyperspectral data has a high spectral resolution, which is superior in discerning minute differences in similar plant species. However, this data is associated with high dimensionality and multicollinearity, which negatively affect the performance of traditional, parametric classification algorithms. To this end, machine algorithms are often preferred to classify hyperspectral data due to their robustness to various data distributions and noise. The current study compared the performance of three advanced machine learning classifiers, i.e., Support Vector Machine (SVM), Random Forest (RF), and Partial Least Squares Discriminant Analysis (PLS-DA), in discriminating four dominant wetland plant species, i.e., Crocosmia sp., Grasses, Agapanthus sp. and Cyperus sp. using simulated hyperspectral data from an upcoming sensor, i.e., nSight-2. The results revealed that SVM is superior, with an overall accuracy of 93.18% (and class-wise accuracies > 85%). In comparison, there were minor differences in the performances of RF and PLS-DA, i.e., 84.09% and 83.63%, respectively. Overall, the results demonstrated that all the evaluated classifiers could achieve acceptable mapping accuracies. However, SVM is more robust, providing exceptional accuracies, and should be considered for operational mapping once the sensor is in space.

Alix-normalized exosomal programmed death-ligand 1 analysis in urine enables precision monitoring of urothelial cancer.

Anti-programmed death-ligand 1 (PD-L1) Ab-based therapies have demonstrated potential for treating metastatic urothelial cancer with high PD-L1 expression. Urinary exosomes are promising biomarkers for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD-L1/Alix ratio to normalize exosomal PD-L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD-L1, and Alix on individual exosomes. On-disc ELISA was used to evaluate PD-L1 and Alix-normalized PD-L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On-disc ELISA was more reliable for detecting exosomal PD-L1 expression than standard plate ELISA-based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD-L1 in urine samples from patients with urothelial cancer.