Pollution levels and probability risk assessment of potential toxic elements in soil of Pb-Zn smelting areas.

Soil pollution around Pb-Zn smelters has attracted widespread attention around the world. In this study, we compiled a database of eight potentially toxic elements (PTEs) Pb, Zn, Cd, As, Cr, Ni, Cu, and Mn in the soil of Pb-Zn smelting areas by screening the published research papers from 2000 to 2023. The pollution assessment and risk screening of eight PTEs were carried out by geo-accumulation index (Igeo), potential ecological risk index (PERI) and health risk assessment model, and Monte Carlo simulation employed to further evaluate the probabilistic health risks. The results suggested that the mean values of the eight PTEs all exceeded the corresponding values in the upper crust, and more than 60% of the study sites had serious Pb and Cd pollution (Igeo > 4), with Brazil, Belgium, China, France and Slovenia having higher levels of pollution than other regions. Besides, PTEs in smelting area caused serious ecological risk (PERI = 10912.12), in which Cd was the main contributor to PREI (86.02%). The average hazard index (HI) of the eight PTEs for adults and children was 7.19 and 9.73, respectively, and the average value of total carcinogenic risk (TCR) was 4.20 × 10-3 and 8.05 × 10-4, respectively. Pb and As are the main contributors to non-carcinogenic risk, while Cu and As are the main contributors to carcinogenic risk. The probability of non-carcinogenic risk in adults and children was 84.05% and 97.57%, while carcinogenic risk was 92.56% and 79.73%, respectively. In summary, there are high ecological and health risks of PTEs in the soil of Pb-Zn smelting areas, and Pb, Cd, As and Cu are the key elements that cause contamination and risk, which need to be paid attention to and controlled. This study is expected to provide guidance for soil remediation in Pb-Zn smelting areas.

[Pollution Assessment and Source Analysis of Heavy Metals in Atmospheric Deposition in a Lead-zinc Smelting City Based on PMF Model].

To explore the pollution characteristics and sources of heavy metals in atmospheric deposition in a typical lead-zinc smelting city, 511 effective atmospheric deposition samples from 22 points in different functional areas of a city in Henan Province were collected monthly during 2021. The concentrations and spatial-temporal distribution of heavy metals were analyzed. The geo-accumulation index method and health risk assessment model were utilized to evaluate the heavy metal pollution degree. The sources of heavy metals were quantitatively analyzed using a positive matrix factorization (PMF) model. The results showed that the average concentrations of ω(Pb), ω(Cd), ω(As), ω(Cr), ω(Cu), ω(Mn), ω(Ni), and ω(Zn) in atmospheric deposition samples were 3185.77, 78.18, 273.67, 149.50, 453.60, 810.37, 54.38, and 2397.38 mg·kg-1, respectively, which were all higher than the soil background values of Henan Province. All heavy metals except Mn had significant seasonal variation characteristics. The concentrations of Pb, Cd, As, and Cu in the industrial area with lead-zinc smelting were significantly higher than those in other functional areas, and the concentration of Zn was the highest in the residential mixed area. The results of the geo-accumulation index showed that the pollution of Cd and Pb were the most serious, followed by that of Zn, Cu, and As, which belonged to the serious-extreme pollution category. The main exposure route of non-carcinogenic risk was hand-mouth intake. Pb and As posed the greatest non-carcinogenic risk to children in all functional areas. The carcinogenic risks of Cr, As, Cd, and Ni through the respiratory system to humans were all below the threshold values. The analysis of the PMF model showed that the main sources of heavy metals in atmospheric deposition were industrial pollution sources (39.7%), transportation sources (28.9%), secondary dust sources (14.4%), incineration and coal combustion sources (9.3%), and natural sources (7.8%).

Screening and characterization of the scFv for chimeric antigen receptor T cells targeting CEA-positive carcinoma.

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy presents a promising treatment option for various cancers, including solid tumors. Carcinoembryonic antigen (CEA) is an attractive target due to its high expression in many tumors, particularly gastrointestinal cancers, while limited expression in normal adult tissues. In our previous clinical study, we reported a 70% disease control rate with no severe side effects using a humanized CEA-targeting CAR-T cell. However, the selection of the appropriate single-chain variable fragment (scFv) significantly affects the therapeutic efficacy of CAR-T cells by defining their specific behavior towards the target antigen. Therefore, this study aimed to identify the optimal scFv and investigate its biological functions to further optimize the therapeutic potential of CAR-T cells targeting CEA-positive carcinoma. Methods: We screened four reported humanized or fully human anti-CEA antibodies (M5A, hMN-14, BW431/26, and C2-45), and inserted them into a 3rd-generation CAR structure. We purified the scFvs and measured the affinity. We monitored CAR-T cell phenotype and scFv binding stability to CEA antigen through flow cytometry. We performed repeated CEA antigen stimulation assays to compare the proliferation potential and response of the four CAR-T cells, then further evaluated the anti-tumor efficacy of CAR-T cells ex vivo and in vivo. Results: M5A and hMN-14 CARs displayed higher affinity and more stable CEA binding ability than BW431/26 and C2-45 CARs. During CAR-T cell production culture, hMN-14 CAR-T cells exhibit a larger proportion of memory-like T cells, while M5A CAR-T cells showed a more differentiated phenotype, suggesting a greater tonic signal of M5A scFv. M5A, hMN-14, and BW431/26 CAR-T cells exhibited effective tumor cell lysis and IFN-γ release when cocultured with CEA-positive tumor cells in vitro, correlating with the abundance of CEA expression in target cells. While C2-45 resulted in almost no tumor lysis or IFN-γ release. In a repeat CEA antigen stimulation assay, M5A showed the best cell proliferation and cytokine secretion levels. In a mouse xenograft model, M5A CAR-T cells displayed better antitumor efficacy without preconditioning. Discussion: Our findings suggest that scFvs derived from different antibodies have distinctive characteristics, and stable expression and appropriate affinity are critical for robust antitumor efficacy. This study highlights the importance of selecting an optimal scFv in CAR-T cell design for effective CEA-targeted therapy. The identified optimal scFv, M5A, could be potentially applied in future clinical trials of CAR-T cell therapy targeting CEA-positive carcinoma.

Facile construction of irinotecan loaded mesoporous nano-formulation with surface-initiated polymerization to improve stimuli-responsive drug delivery for breast cancer therapy.

This work uses rice husk to fabricate mesoporous silica nanoparticles (D-RMN) for breast cancer therapy. The biocompatible dual-responsive (DAN-RMN) was developed by polymerizing acrylic acid (AA) and n-isopropyl acrylamide (NIPAM) on the DV-RMN surface monomeric ratio to increase drug delivery efficiency after vinyl groups were added to the surface of nanoparticles (DAN-RMN). Various analytical and spectroscopical methods characterized the fabricated nanoparticles. Additionally, further encapsulation with SN-38 into the DAN-RMN enhances anticancer efficiency. The in-vitro controlled SN-38 release displayed remarkable temperature and pH response. The MTT assay established the biocompatibility and cytotoxicity of natural sources of silica and DAN-RMN. The fabricated SN-38@DAN-RMN nanoparticles effectively killed the MDA-MB-231 and 4T1 cancerous cells, confirmed by the MTT assay. The IC50 values of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 1.8 µg/mL and 1.7 µg/mL, respectively. In addition, acridine orange-ethidium bromide (AO-EB) dual staining methods were used to determine morphological changes of cell shrinkage and fragmentation. Nuclear staining methods confirmed the nuclear fragmentation and condensation of the cells. Further, the cell death was examined using dual staining Annexin V-FITC/PI in flow cytometric analyses to assess apoptosis in the MDA-MB-231 and 4T1 cell lines. The apoptotic cell ratio of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 27.8 and 32.8, respectively. Since there is no drug leakage in the blood while the carrier is in circulation, the DAN-RMN nanocarrier may be used for targeted and stimuli-responsive administration using ultrasound imaging.

Comparison of two different flexible laryngeal airway masks in pediatric ophthalmic surgeries: A retrospective study.

This study aimed to compare the clinical effects of the Medis flexible laryngeal mask airway (FLMA) with those of the Ambu AuraFlex FLMA in pediatric ophthalmic surgery. A total of 80 patients, aged 1 to 5 years, in American Society of Anesthesiologists I-II, weighing ≥10 kg, and without any existing airway difficulties, were enrolled in this study. The patients were randomly divided into Group M (Medis FLMA) and Group A (Ambu AuraFlex FLMA). The time of insertion, number of attempts, finger assistance required, manipulation, oropharyngeal leak pressure (OLP), fiberoptic grade of view, and complications such as bloodstaining, hoarseness, and sore throat were recorded. Group M showed a significantly higher OLP than did Group A (P = .002); however, Group M required more finger assistance than did Group A (P = .009). There were no statistically significant differences between the 2 groups in terms of insertion time, number of attempts, manipulation, fiberoptic view grade, or complications. Both the Medis and Ambu AuraFlex FLMA can provide smooth ventilation during pediatric ophthalmic surgeries. The Medis FLMA showed a higher OLP than did the Ambu AuraFlex FLMA but required more finger assistance during insertion.

CD27 agonism coordinates with CD28 and 4-1BB signal to augment the efficacy of CAR-T cells in colorectal tumor.

Chimeric antigen receptor T cell (CAR-T) is regarded as a promising therapy for malignancies. In our previous clinical trial targeted colorectal tumors, we found that CAR-T cells experienced poor proliferation and persistence in tumor sites. To improve the efficacy of CAR-T cells, we introduced CD27 co-stimulation signal into the established system and found that the CEA28BB27Z CAR-T cells exhibited enhanced proliferation and anti-tumor activity. Next, we demonstrated that the CEA28BB27Z CAR-T cells expressed less immune checkpoint receptors and generated more CD4+ and CD8+ memory stem T (TSCM) cells compared with other CARs during constant antigen stimulation. Furthermore, our data revealed that the different combination of co-stimulation signal affected the mitochondrial dynamics of CAR-T cells, and CEA28BB27Z CAR-T cells maintained more fused mitochondrial network compared with others. Finally, we validated the superior antitumor capacity of the CEA28BB27Z CAR-T cells in xenograft models. Our findings suggest that CD27 co-stimulation signals play a key role in improving the anti-tumor efficacy of CAR-T cells.

Reduction of cadmium bioavailability in paddy soil and its accumulation in brown rice by FeCl3 washing combined with biochar: A field study.

Cadmium (Cd) removal from paddy soil to reduce Cd accumulation in brown rice is essential for agroecology, food safety, and human health. In this study, we demonstrate that ferric chloride (FeCl3) washing combined with biochar treatment efficiently remediates Cd-contaminated paddy soil in field trials. Our results showed that 30.9 % of total Cd and 41.6 % of bioavailable Cd were removed by the addition of 0.03 M FeCl3 at a liquid/soil ratio of 1.5:1. The subsequent addition of 1 % biochar further reduced bioavailable Cd by 36.5 and 41.5 %, compared with FeCl3 washing or biochar treatment alone. The principal component regression analysis showed that the Cd content in brown rice was primarily affected by the bioavailable Cd in soil. The combined remediation contributed to the decreased Cd contents in brown rice by 45.5-62.5 %, as well as a 2.7-11.8 % increase in rice yield. The Cd contents in brown rice decreased to 0.12 and 0.04 mg kg-1 in two cultivars of rice (Zhuliangyou189 and Zhuliangyou929), lower than the national food safety standard limit value of China (0.2 mg kg-1). Meanwhile, the combined remediation promoted the restoration of soil pH and organic matter as well as the improvement of available nutrients. This finding suggests that the combination of FeCl3 washing and biochar is an effective remediation strategy to minimize Cd bioavailability in paddy soil, and improves soil quality, thus contributing to food safety.

Cost-Effectiveness of Posaconazole vs. First-Generation Triazoles for the Prevention of Invasive Fungal Infections Among High-Risk Patients With Hematological Malignancies in China.

Background: Posaconazole is confirmed to be more effective for preventing invasive fungal infections (IFIs) than first-generation triazoles (fluconazole and itraconazole), but its economic value has not been comprehensively evaluated in China. This study compared the cost-effectiveness of these two antifungal prophylaxis regimens in hematological-malignancy patients at high risk for IFIs from the Chinese healthcare perspective. Methods: A hybrid decision tree and Markov model were built using published data to estimate the total costs and quality-adjusted life-years (QALYs) of antifungal prophylaxis with posaconazole oral suspension and first-generation triazoles. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the threshold of willingness to pay (WTP) were considered cost-effective. One-way and probabilistic sensitivity analyses were performed to assess model robustness. The regional imbalance of economic development and the tablet formulation of posaconazole were considered in the scenario analyses. Results: In the base-case analysis, posaconazole oral suspension provided an additional 0.109 QALYs at an incremental cost of $954.7, yielding an ICER of $8,784.4/QALY, below the national WTP threshold of $31,315/QALY. One-way and probabilistic sensitivity analyses showed that the results were robust. Scenario analyses showed that the base-case ICER was consistently below the WTP thresholds of all 31 Chinese provinces, with the likelihood of posaconazole being cost-effectiveness ranging from 78.1 to 99.0%. When the posaconazole oral suspension was replaced by the tablet formulation, the ICER increased to $29,214.1/QALY, still below the national WTP threshold and WTP thresholds of 12 provinces. Conclusions: Posaconazole oral suspension is a highly cost-effective regimen for preventing IFI in high-risk hematological-malignancy patients from the Chinese healthcare perspective. Posaconazole tablets may also be considered in some high-income regions of China.

Lenvatinib Combined With a PD-1 Inhibitor as Effective Therapy for Advanced Intrahepatic Cholangiocarcinoma.

Background: Lenvatinib combined with a PD-1 inhibitor has obtained a satisfactory antitumor effect in several solid tumors. However, the efficacy and tumor response of lenvatinib with a PD-1 inhibitor in advanced intrahepatic cholangiocarcinoma still need further exploration. Methods: This is a single-arm study for the assessment of the efficacy and tolerability of lenvatinib with a PD-1 inhibitor in intrahepatic cholangiocarcinoma patients who had chemotherapy failure. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Results: A total of 40 patients with advanced intrahepatic cholangiocarcinoma were enrolled after the chemorefractory effect. The median progression-free survival was 5.83 ± 0.76 months. The 3-month and 6-month progression-free survival rates were 80.0% and 32.5%, respectively. The median overall survival was 14.30 ± 1.30 months. The 12-month and 18-month overall survival rates were 61.4% and 34.7%. The 3-month RECIST 1.1 evaluation was that seven patients (17.5%) showed partial response, 23 patients (57.5%) had stable disease, and 10 patients (25.0%) had progressive disease. The objective response rate was 17.5%, and the disease control rate was 75.0%. All the recorded any-grade adverse events inducing treatment termination were controllable, and there were no AE-related deaths. Conclusion: Our study showed that a combination of lenvatinib with the PD-1 inhibitor could be an effective treatment for advanced intrahepatic cholangiocarcinoma after the chemorefractory effect.

Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta-analysis.

BACKGROUND: An increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta-analysis to estimate the incidence, risk factors and outcomes of IPA in patients with influenza. METHODS: A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases from their inception to 31 August 2021 for eligible studies. Data on the incidence and risk factors of and mortality due to IPA in influenza patients were pooled using a random-effects model. Sensitivity analyses restricted to severe influenza requiring intensive care unit (ICU) support and multiple subgroup analyses were performed. RESULTS: Fourteen studies involving 6024 hospitalised patients with influenza were included. IPA was estimated to occur in 10% of influenza patients, with a mortality rate of 52%. Similar incidence (11%) and mortality (54%) estimates for IPA were observed in the sensitivity analysis including severe cases requiring ICU support. Subgroup analysis by geographical location showed a similar IPA rate between European (10%) and non-European (11%) studies. The IPA rate in the subset of nine studies using the modified AspICU criteria was 13%. Most subgroup analyses showed ≥50% mortality in IPA patients. Several predictors for IPA susceptibility were identified, including male sex, smoking history, chronic lung disease, influenza A (H1N1), severe conditions requiring supportive therapy, corticosteroid use before admission, solid organ transplant and haematological malignancy. CONCLUSIONS: The IPA is common in individuals with severe influenza, and the prognosis is particularly poor. Influenza patients, especially those with high-risk factors, should be thoroughly screened for IPA.

Long Non-coding RNA MALAT1 Alleviates the Elevated Intraocular Pressure (Eiop)-induced Glaucoma Progression via Sponging miR-149-5p.

Background: Glaucoma is an optic neuropathic disease and contributed to the irreversible blindness caused by the slow death of retinal ganglion cells (RGCs). Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be aberrantly expressed in diverse diseases, including glaucoma. However, the mechanism of MALAT1 in glaucoma was still undefined.Methods: The levels of MALAT1, microRNA-149-5p (miR-149-5p) in RGCs cultured under elevated pressure were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The putative target of MALAT1 was predicted by starBase v2.0 online database, and dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were performed to verify this interaction. The cell viability of RGCs was measured by Cell Counting Kit-8 (CCK-8) assay. The apoptotic rate was evaluated via flow cytometry. The protein levels of apoptosis-related proteins (Bax, B-cell lymphoma 2 (Bcl-2)) and Cleaved caspase 3 were assessed by Western blot.Results: The level of MALAT1 was significantly down-regulated, and the level of miR-149-5p was distinctly up-regulated in RGCs under pressure in a dose-dependent manner. Functionally, MALAT1 overexpression or miR-149-5p inhibitor alleviated the inhibitory effect on cell viability and the promoted effect on apoptotic rate of RGCs in EIOP. The interaction between MALAT1 and miR-149-5p was predicted by starBase v2.0 online database, and dual luciferase reporter assay, RIP assay and RNA pull-down assay validated the interaction. Combined with the loss and gain experiment results, miR-149-5p was negatively interacted with MALAT1. Furthermore, miR-149-5p mimics mitigated the promoted impact on cell viability and the suppressive impact on apoptotic rate by targeting MALAT1.Conclusion: MALAT1 promoted cell proliferation and inhibited cell apoptosis of RGCs via targeting miR-149-5p in glaucoma in vitro, which might shed light on the mechanism of glaucoma pathogenesis.

ISO/IEEE 11073 Treadmill Interoperability Framework and its Test Method: Design and Implementation.

BACKGROUND: Regular physical activity is proven to help prevent and treat noncommunicable diseases such as heart disease, stroke, diabetes, and breast and colon cancer. The exercise data generated by health and fitness devices (eg, treadmill, exercise bike) are very important for health management service providers to develop personalized training programs. However, at present, there is little research on a unified interoperability framework in the health and fitness domain, and there are not many solutions; besides, the privatized treadmill data transmission scheme is not conducive to data integration and analysis. OBJECTIVE: This article will expand the IEEE 11073-PHD standard protocol family, develop standards for health and fitness device (using treadmill as an example) based on the latest version of the 11073-20601 optimized exchange protocol, and design protocol standards compliance testing process and inspection software, which can automatically detect whether the instantiated object of the treadmill meets the standard. METHODS: The study includes the following steps: (1) Map the data transmitted by the treadmill to the 11073-PHD objects; (2) Construct a programming language structure corresponding to the 11073-PHD application protocol data unit (APDU) to complete the coding and decoding part of the test software; and (3) Transmit the instantiated simulated treadmill data to the gateway test software through transmission control protocol for standard compliance testing. RESULTS: According to the characteristics of the treadmill, a data exchange framework conforming to 11073-PHD is constructed, and a corresponding testing framework is developed; a treadmill agent simulation is implemented, and the interoperability test is performed. Through the designed testing process, the corresponding testing software was developed to complete the standard compliance testing of the treadmill. CONCLUSIONS: The extended research of IEEE 11073-PHD in the field of health and fitness provides a potential new idea for the data transmission framework of sports equipment such as treadmills, which may also provide some help for the development of sports health equipment interoperability standards.

Remediation of hexachlorobenzene-contaminated soils with alkyl glycoside-enhanced desorption and zero-valent iron-EDTA-air treatment.

In this work, the use of a coupled process, alkyl glycoside (APG) enhanced soil desorption followed by the zero-valent iron-ethylenediaminetetraacetic acid (EDTA)-air (ZEA) Fenton-like system, was investigated for the remediation of a simulated hexachlorobenzene (HCB)-contaminated diatomite soil and a real HCB-contaminated soil. Three surfactants with different concentrations were studied to obtain the suitable soil desorption agent. Compared with APG0810 and Triton x-100, APG0814 showed a better solubilization effect due to its lower critical micelle concentration. With addition of 3000 mg L-1 APG0814, 35% of HCB was removed from contaminated diatomite soil, and a small amount of residual APG in diatomite soil was found to be beneficial for the soil dispersion. After treatment with the ZEA system, the removal efficiency of HCB in the diatomite soil desorption solution reached 76% in 2 h; we observed that a small amount of APG retained in the desorption solution accelerated the HCB removal. A real HCB-contaminated soil was used to verify the remediation effects. This study demonstrates that our approach is a feasible alternative for remediating soil contaminated with hydrophobic organic compounds.

Matrine suppresses breast cancer metastasis by targeting ITGB1 and inhibiting epithelial-to-mesenchymal transition.

Metastasis can be a fatal step in breast cancer progression. Effective therapies are urgently required due to the limited therapeutic options clinically available. The aim of the present study was to investigate the effect of matrine (MAT), a traditional Chinese medicine, on the proliferation and migration of human breast cancer cells and its underlying mechanisms of action. The proliferation of MDA-MB-231 cells was inhibited and apoptosis was induced following treatment with MAT, as determined by MTT and Annexin-V-FITC/PI assays. Western blot analysis was used to detect the LC-3II/I levels and the results suggested that tumor autophagy is involved in the anti-tumor activity of MAT. To the best of our knowledge, this is the first study to report that MAT inhibits MDA-MB-231 and MCF-7 cell motility, potentially by targeting integrin ß1 (ITGB1) and epithelial-to-mesenchymal transition (EMT), as indicated by Transwell® and siRNA interference assays. In conclusion, ITGB1 and EMT are involved in MAT-induced breast carcinoma cell death and the inhibition of metastasis. This may lead to the development of novel compounds for the treatment of breast cancer metastasis.

Sustained Therapeutic Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Acute Lymphoblastic Leukemia.

PURPOSE: Immunogenicity derived from the murine scFv, a major molecular compomemt of chimeric antigen receptors (CARs), may limit the persistence of CAR T cells, resulting in tumor relapse of patients in complete remission (CR). In this study, we developed a humanized anti-CD19 scFv CAR-T (hCAR-T) to treat patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). PATIENTS AND METHODS: In this one-arm, open-labeled study, we infused the T cells modified with hCAR to patients with r/r ALL. Patients were evaluated with long-term follow-up for response and safety of the treatment. The study was registered at Clinicaltrials.gov (NCT02349698). RESULTS: Ten patients with r/r ALL were recruited for this study. All were response evaluable and all achieved CR; eight patients remained CR, and six were in CR for over 18 months without further treatment. A long-term persistence of hCAR T cells was observed in most of the patients. Among these patients, four of them with high tumor burden and rapidly progressive disease (median, 58%) experienced grade 3-4 cytokine release syndrome (CRS) and neurotoxicity. These severe CRSs were successfully controlled by tocilizumab, glucocorticoid, and plasma exchange. CONCLUSIONS: T cells expressing the humanized anti-CD19 scFv CARs exhibited sustained therapeutic efficacy in the treatment of r/r ALL. Low replase rate was associated with the long-term persistence of CAR T cells.

A critical review of risks, characteristics, and treatment strategies for potentially toxic elements in wastewater from shale gas extraction.

Shale gas extraction via horizontal drilling and hydraulic fracturing (HF) has enhanced gas production worldwide, which has altered global energy markets and reduced the prices of natural gas and oil. Water management has become the most challenging issue of HF, as it demands vast amounts of freshwater and generates high volumes of complex liquid wastes contaminated by diverse potentially toxic elements at variable rates. This critical review focuses on characterizing HF wastewater and establishing strategies to mitigate environmental impacts. High prioritization was given to the constituents with mean concentrations over 10 times greater than the maximum contamination level (MCL) guidelines for drinking water. A number of potentially harmful organic compounds in HF wastewaters were identified via the risk quotient approach to predict the associated toxicity for freshwater organisms in recipient surface waters. Currently, two options for HF wastewater treatment are preferred, i.e., disposal by deep well injection or on-site re-use as a fracturing fluid. Supplementary treatment will be enforced by increasingly rigorous regulations. Partial treatment and reuse remain the preferred method for managing HF wastewater where feasible. Otherwise, advanced technologies such as membrane separation/distillation, forward osmosis, mechanical vapor compression, electrocoagulation, advanced oxidation, and adsorption-biological treatment will be required to satisfy the sustainable requirements for reuse or surface discharge.

The Ibr-7 derivative of ibrutinib exhibits enhanced cytotoxicity against non-small cell lung cancer cells via targeting of mTORC1/S6 signaling.

Ibrutinib is a small molecule drug that targets Bruton's tyrosine kinase in B-cell malignancies and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia. However, the anti-cancer activity of ibrutinib against solid tumors, such as non-small cell lung cancer (NSCLC), remains low. To improve the cytotoxicity of ibrutinib towards lung cancer, we synthesized a series of ibrutinib derivatives, of which Ibr-7 exhibited superior anti-cancer activity to ibrutinib, especially against epithelial growth factor receptor (EGFR) wild-type NSCLC cell lines. Ibr-7 was observed to dramatically suppress the mammalian target of Rapamycin complex 1 (mTORC1)/S6 signaling pathway, which is only slightly affected by ibrutinib, thus accounting for the superior anti-cancer activity of Ibr-7 towards NSCLC. Ibr-7 was shown to overcome the elevation of Mcl-1 caused by ABT-199 mono-treatment, and thus exhibited a significant synergistic effect when combined with ABT-199. In conclusion, we used a molecular substitution method to generate a novel ibrutinib derivative, termed Ibr-7, which exhibits enhanced anti-cancer activity against NSCLC cells as compared with the parental compound.

Multifunctional iron-biochar composites for the removal of potentially toxic elements, inherent cations, and hetero-chloride from hydraulic fracturing wastewater.

This paper evaluates a novel sorbent for the removal of potentially toxic elements, inherent cations, and hetero-chloride from hydraulic fracturing wastewater (FWW). A series of iron-biochar (Fe-BC) composites with different Fe/BC impregnation mass ratios (0.5:1, 1:1, and 2:1) were prepared by mixing forestry wood waste-derived BC powder with an aqueous FeCl3 solution and subsequently pyrolyzing them at 1000 °C in a N2-purged tubular furnace. The porosity, surface morphology, crystalline structure, and interfacial chemical behavior of the Fe-BC composites were characterized, revealing that Fe chelated with CO bonds as COFe moieties on the BC surface, which were subsequently reduced to a CC bond and nanoscale zerovalent Fe (nZVI) during pyrolysis. The performance of the Fe-BC composites was evaluated for simultaneous removal of potentially toxic elements (Cu(II), Cr(VI), Zn(II), and As(V)), inherent cations (K, Na, Ca, Mg, Ba, and Sr), hetero-chloride (1,1,2-trichlorethane (1,1,2-TCA)), and total organic carbon (TOC) from high-salinity (233 g L-1 total dissolved solids (TDS)) model FWW. By elucidating the removal mechanisms of different contaminants, we demonstrated that Fe-BC (1:1) had an optimal reducing/charge-transfer reactivity owing to the homogenous distribution of nZVI with the highest Fe0/Fe2+ ratio. A lower Fe content in Fe-BC (0.5:1) resulted in a rapid exhaustion of Fe0, while a higher Fe content in Fe-BC (2:1) caused severe aggregation and oxidization of Fe0, contributing to its complexation/(co-)precipitation with Fe2+/Fe3+. All of the synthesized Fe-BC composites exhibited a high removal capacity for inherent cations (3.2-7.2 g g-1) in FWW through bridging with the CO bonds and cation-π interactions. Overall, this study illustrated the potential efficacy and mechanistic roles of Fe-BC composites for (pre-)treatment of high-salinity and complex FWW.

Spore morphology and ultrastructure of an Ascosphaera apis strain from the honeybees (Apis mellifera) in southwest China.

Ascosphaera apis is an intestinally infective, spore-forming, filamentous fungus that infects honeybees and causes deadly chalkbrood disease. Although A. apis has been known for 60 y, little is known about the ultrastructure of the spores. In this study, the fine morphology and ultrastructure of an isolate, A. apis CQ1 from southwest China, was comprehensively identified by transmission electron microscopy, confocal laser scanning microscopy, scanning electron microscopy, and optical microscopy. The high sequence similarity and phylogenetic data based on nuc rDNA ITS1-5.8S-ITS2 (ITS) supported the hypothesis that the CQ1 strain is a new member of the A. apis species. Morphological observation indicated that the mature spores are long ovals with an average size of 2 × 1.2 µm and are tightly packed inside spherical spore balls. More than 10 spore balls that were 8-16 µm in diameter were wrapped and formed a spherical, nearly hyaline spore cyst of 50-60 µm in diameter. Ultrastructural analysis showed that mature spores have two nuclei with distinctly different sizes. A large nucleus with double nuclear membranes was found in the center of the spore, whereas the small nucleus was only one-fifth of the large nucleus volume and was located near the end of the spore. Numerous ribosomes filled the cytoplasm, and many mitochondria with well-defined structures were arranged along the inner spore wall. The spore wall consists of an electron-dense outer surface layer, an electron-lucent layer, and an inner plasma membrane. Chitin is the major component of the spore wall. The germinated spore was observed as an empty spore coat, whereas the protoplasts, including the nuclei, mitochondria, and ribosomes, had been discharged. In addition to these typical fungal spore organelles, an unknown electron-dense regular structure might be the growing mycelium, which was arranged close to the inner spore wall and almost covered the entire wall area.