Decision fatigue experience of front-line nurses in the context of public health emergency: an interpretative phenomenological analysis.

BACKGROUND: Decision fatigue is a new concept in the field of psychology and refers to a state of fatigue alongside impaired cognitive processing and emotional regulation ability. Previous studies have confirmed that nurses are prone to decision fatigue, and nurses who experience decision fatigue may implement nursing measures that are inconsistent with clinical evidence, thus affecting patients' benefits. COVID-19, as a large-scale global public health emergency, increased the workload and burden of nurses and aggravated decision fatigue. However, the factors leading to decision fatigue among nurses have not yet been identified. METHODS: This study is guided by interpretative phenomenology. During the epidemic period of COVID-19: From November 2022 to February 2023, a one-to-one, semi-structured in-depth interview was conducted among nurses with decision fatigue experience who were participating in front-line work in Jilin Province using homogenous sampling. The interview recordings and related data were transcribed into text within 24 h, and data analysis was assisted by NVivo 12.0 software. RESULTS: After a total of 14 front-line nurses were analyzed in this study, The thematic level reaches saturation, the findings present a persuasive and coherent narrative, and the study is terminated, and finally extracted and formed three core themes: "Cognition, influence and attitude of decision fatigue", "Approaching factors of decision fatigue" and "Avoidant factors of decision fatigue". CONCLUSION: This study confirmed that decision fatigue was widespread in the work of front-line nurses, affecting the physical and psychological health of nurses, the quality of nursing work, the degree of benefit of patients and the clinical outcome. However, nursing staff do not know enough about decision fatigue, so the popularization and research of decision fatigue should be strengthened. Improve the attention of medical institutions, nursing managers and nursing staff.Some suggestions are put forward for the intervention of decision fatigue through personnel, task, tool and technology, organization and environment.

Interaction between microalgae and phycosphere bacteria in a binary cultivation system-based dairy farm wastewater treatment.

The combination of microalgal culture and wastewater treatment is an emerging topic. This study investigated the use of different microalgae to treat different types of dairy farm wastewater. The results showed that the removal of ammonia nitrogen and total phosphorus by mixed microalgae was over 99% and 80%, respectively. The highest production of protein in biomass and extracellular polymeric substances was observed in high-concentration wastewater. In the phycosphere, the abundance of Proteobacteria and Cyanobacteria increased, while that of Bacteroidota decreased. Phycosphere bacteria were strongly correlated with microalgal growth and the composition of extracellular polymeric substances, especially with bound extracellular polymeric substances relative to soluble extracellular polymeric substances. Genes associated with photosynthesis and respiration in phycosphere bacteria were upregulated, contributing to the material exchange capacity in the microalgal-bacterial systems. The interaction between microalgae and phycosphere bacteria thus represents the core of the binary cultivation system-based wastewater treatment and requires further investigation.

Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinoma.

Solid carcinomas are often highly heterogenous cancers, arising from multiple epithelial cells of origin. Yet, how the cell of origin influences the response of the tumor microenvironment is poorly understood. Lung adenocarcinoma (LUAD) arises in the distal alveolar epithelium which is populated primarily by alveolar epithelial type I (AT1) and type II (AT2) cells. It has been previously reported that Gramd2 + AT1 cells can give rise to a histologically-defined LUAD that is distinct in pathology and transcriptomic identity from that arising from Sftpc + AT2 cells1,2. To determine how cells of origin influence the tumor immune microenvironment (TIME) landscape, we comprehensively characterized transcriptomic, molecular, and cellular states within the TIME of Gramd2 + AT1 and Sftpc + AT2-derived LUAD using KRASG12D oncogenic driver mouse models. Myeloid cells within the Gramd2 + AT1-derived LUAD TIME were increased, specifically, immunoreactive monocytes and tumor associated macrophages (TAMs). In contrast, the Sftpc + AT2 LUAD TIME was enriched for Arginase-1+ myeloid derived suppressor cells (MDSC) and TAMs expressing profiles suggestive of immunosuppressive function. Validation of immune infiltration was performed using flow cytometry, and intercellular interaction analysis between the cells of origin and major myeloid cell populations indicated that cell-type specific markers SFTPD in AT2 cells and CAV1 in AT1 cells mediated unique interactions with myeloid cells of the differential immunosuppressive states within each cell of origin mouse model. Taken together, Gramd2 + AT1-derived LUAD presents with an anti-tumor, immunoreactive TIME, while the TIME of Sftpc + AT2-derived LUAD has hallmarks of immunosuppression. This study suggests that LUAD cell of origin influences the composition and suppression status of the TIME landscape and may hold critical implications for patient response to immunotherapy.

Regulation and microbial response mechanism of nitric oxide to copper-containing swine wastewater treated by Pistia stratiotes.

As a signaling molecule, Nitric oxide (NO) has been widely used in abiotic stress mitigation studies.Pistia stratiotes showed a good synergistic removal effect on heavy metals, nitrogen and phosphorus, but the high concentration of copper(Cu) in swine wastewater inhibited the comprehensive removal ability of Pistia stratiotes. At present, it is not clear how the addition of NO regulates the stress resistance mechanism of Pistia stratiotes to copper in swine wastewater, and the microbial response mechanism accompanying this process is not yet clear. Therefore, in the concentration range of 0.31∼4 mg·L-1Cu2+ and NO concentration of 0,0.05 and 0.1 mg L-1, the removal effect of Pistia stratiotes on copper from swine wastewater was studied. The results showed as follows: The treatment of non-available copper in groups M and H increased by 10.67% and 22.31%, respectively, compared with that in group L. The critical point of inhibiting effect of NO on growth rate was 2.03 mg·L-1Cu. By measuring three-dimensional fluorescence spectrum, combined with parallel factor analysis and principal component analysis, it was confirmed that exogenous addition of NO affected the humification degree of dissolved organic matter(DOM) and promoted the chelation of organic matter with copper. With the increase of Cu concentration, the Reyranella and Prosthecobacter with certain copper resistance gradually gained advantages. Redundancy analysis(RDA) showed that Emiticicia had a strong correlation with the removal rates of ammonia nitrogen, total phosphorus and copper in swine wastewater, while hgcI_clade had a strong correlation with the removal rates of total nitrogen. In conclusion, controlling the dosage of NO can effectively improve the tolerance and removal effect of Pistia stratiotes on copper in swine wastewater, which is of great significance for promoting the treatment and resource transformation of swine wastewater.

Suvemcitug plus chemotherapy for platinum-resistant epithelial ovarian, fallopian tube and primary peritoneal cancer: A phase 1b dose-escalation trial.

OBJECTIVE: The use of bevacizumab has been hampered by safety concerns despite demonstrable progression-free survival (PFS) benefit in subjects with platinum-resistant ovarian cancer, highlighting the need for novel effective and safe antiangiogenic agents. This study aimed to characterize the tolerability, safety, and antitumor activities of escalating doses of anti-VEGF antibody suvemcitug plus chemotherapy in platinum-resistant ovarian cancer patients. METHODS: This open-label, dose-escalation trial enrolled adult patients (≥18 years) with platinum-resistant histologically or cytologically-confirmed epithelial ovarian, fallopian tube and primary peritoneal cancer. Eligible patients received paclitaxel or topotecan plus escalating doses of suvemcitug 0.5, 1, 1.5, or 2 mg/kg once every two weeks. The primary endpoints were safety and tolerability, and antitumor activities of suvemcitug. RESULTS: Twenty-nine subjects received paclitaxel (n = 11) or topotecan (n = 18). No dose-limiting toxicities occurred. The most common adverse events of special interest were proteinuria (41.4%), hypertension (20.7%) and epistaxis (10.3%). No gastrointestinal perforations occurred. Nine subjects (31.0%, 95% CI 15.3-50.8) demonstrated investigators-confirmed objective response, including complete response in 1 and partial response in 8. The median PFS was 5.4 months (95% CI 2.2-7.4). CONCLUSIONS: Suvemcitug demonstrated an acceptable safety profile and promising antitumor activities in platinum-resistant ovarian cancer patients, supporting its further clinical development.

M2 macrophage-derived exosomal circTMCO3 acts through miR-515-5p and ITGA8 to enhance malignancy in ovarian cancer.

Tumor-associated macrophages of the M2 phenotype promote cancer initiation and progression. Importantly, M2 macrophage-derived exosomes play key roles in the malignancy of cancer cells. Here, we report that circTMCO3 is upregulated in ovarian cancer patients, and its high expression indicates poor survival. M2-derived exosomes promote proliferation, migration, and invasion in ovarian cancer, but these effects are abolished by knockdown of circTMCO3. Furthermore, circTMCO3 functions as a competing endogenous RNA for miR-515-5p to reduce its abundance, thus upregulating ITGA8 in ovarian cancer. miR-515-5p inhibits ovarian cancer malignancy via directly downregulating ITGA8. The decreased oncogenic activity of circTMCO3-silencing exosomes is reversed by miR-515-5p knockdown or ITGA8 overexpression. Exosomal circTMCO3 promotes ovarian cancer progression in nude mice. Thus, M2 macrophage-derived exosomes promote malignancy by delivering circTMCO3 and targeting the miR-515-5p/ITGA8 axis in ovarian cancer. Our findings not only provide mechanistic insights into ovarian cancer progression, but also suggest potential therapeutic targets.

A cuproptosis-related signature predicts prognosis and indicates cross-talk with immunocyte in ovarian cancer.

PURPOSE: Cuproptosis, programmed cell death by intracellular copper-mediated lipoylated protein aggregation, is involved in various tumorigenesis and drug resistance abilities by mediating the tumor microenvironment. Previous studies have demonstrated that serum copper levels are higher in OC patients than in normal subjects. However, the exact relationship between cuproptosis and ovarian cancer progression remains to be further elucidated. METHODS: The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) datasets were utilized to establish a cuproptosis-related prognostic signature in ovarian cancer. Subsequently, the bulk RNA-seq analysis and single-cell RNA-seq analysis were used to identify the relationship between signature with immune cell infiltration, chemotherapy, and cuproptosis-related scoring (CuRS) system. Finally, the potential biological functional roles of target genes in cuproptosis were validated in vitro. RESULTS: By using LASSO-Cox regression analysis to establish the cuproptosis-related prognostic model, our works demonstrated the accuracy and efficiency of our model in the TCGA (583 OC patients) and GEO (260 OC patients) OC cohorts, and the high-scoring groups showed worse survival outcomes. Notably, there were substantial differences between the high and low-risk groups in extensive respects, such as the activating transcription factors, cell pseudotime features, cell intercommunication patterns, immunocytes infiltration, chemotherapy response, and potential drug resistance. KIF26B was selected to construct a prognostic model from the identified 33 prognosis-related genes, and high expression of KIF26B predicted poorer prognosis in ovarian cancer. Ultimately, further in vitro experiments demonstrated that KIF26B participated in the proliferation and cisplatin resistance of OC cells. Knockdown of KIF26B increased the sensitivity of OC cells to elesclomol, a cuproptosis agonists. CONCLUSION: This study constructed a new cuproptosis-related gene signature that has a good prognostic capacity in assessing the outcome of OC patients. This study enhances our understanding of cuproptosis associated with ovarian cancer aggressiveness, cross-talk with immunocytes, and serves as a novel chemotherapy strategy.

Microalgal-bacterial consortia for the treatment of livestock wastewater: Removal of pollutants, interaction mechanisms, influencing factors, and prospects for application.

The livestock sector is responsible for a significant amount of wastewater globally. The microalgal-bacterial consortium (MBC) treatment has gained increasing attention as it is able to eliminate pollutants to yield value-added microalgal products. This review offers a critical discussion of the source of pollutants from livestock wastewater and the environmental impact of these pollutants. It also discusses the interactions between microalgae and bacteria in treatment systems and natural habitats in detail. The effects on MBC on the removal of various pollutants (conventional and emerging) are highlighted, focusing specifically on analysis of the removal mechanisms. Notably, the various influencing factors are classified into internal, external, and operating factors, and the mutual feedback relationships between them and the target (removal efficiency and biomass) have been thoroughly analysed. Finally, a wastewater recycling treatment model based on MBC is proposed for the construction of a green livestock farm, and the application value of various microalgal products has been analysed. The overall aim was to indicate that the use of MBC can provide cost-effective and eco-friendly approaches for the treatment of livestock wastewater, thereby advancing the path toward a promising microalgal-bacterial-based technology.

Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD.

The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2.86 and JN.1 raise concerns regarding their potential to evade immune surveillance and spread globally. Here, we test sera from rhesus macaques immunized with 3 doses of wild-type SARS-CoV-2 receptor-binding domain (RBD)-Fc adjuvanted with the STING agonist CF501. We find that the sera can potently neutralize pseudotyped XBB.1.5, XBB.1.16, CH.1.1, EG.5, BA.2.86, and JN.1, with 50% neutralization titers ranging from 3,494 to 7,424. We also demonstrate that CF501, but not Alum, can enhance immunogenicity of the RBD from wild-type SARS-CoV-2 to improve induction of broadly neutralizing antibodies (bnAbs) with binding specificity and activity similar to those of SA55, BN03, and S309, thus exhibiting extraordinary broad-spectrum neutralizing activity. Overall, the RBD from wild-type SARS-CoV-2 also contains conservative epitopes. The RBD-Fc adjuvanted by CF501 can elicit potent bnAbs against JN.1, BA.2.86, and other XBB subvariants. This strategy can be adopted to develop broad-spectrum vaccines to combat future emerging and reemerging viral infectious diseases.

Vermicompost: In situ retardant of antibiotic resistome accumulation in cropland soils.

The dissemination of antibiotic resistance genes (ARGs) in soil has become a global environmental issue. Vermicomposting is gaining prominence in agricultural practices as a soil amendment to improve soil quality. However, its impact on soil ARGs remains unclear when it occurs in farmland. We comprehensively explored the evolution and fate of ARGs and their hosts in the field soil profiles under vermicompost application for more than 3 years. Vermicompost application increased several ARG loads in soil environment but decreased the high-risk bla-ARGs (blaampC, blaNDM, and blaGES-1) by log(0.04 - 0.43). ARGs in soil amended with vermicompost primarily occurred in topsoil (approximately 1.04-fold of unfertilized soil), but it is worth noting that their levels in the 40-60 cm soil layer were the same or even less than in the unfertilized soil. The microbial community structure changed in soil profiles after vermicompost application. Vermicompost application altered the microbial community structure in soil profiles, showing that the dominant bacteria (i.e., Proteobacteria, Actinobacteriota, Firmicutes) were decreased 2.62%-5.48% with the increase of soil depth. A network analysis further revealed that most of ARG dominant host bacteria did not migrate from surface soil to deep soil. In particular, those host bacteria harboring high-risk bla-ARGs were primarily concentrated in the surface soil. This study highlights a lower risk of the propagation of ARGs caused by vermicompost application and provides a novel approach to reduce and relieve the dissemination of ARGs derived from animals in agricultural production.

Tracking the extracellular and intracellular antibiotic resistance genes across whole year in wastewater of intensive dairy farm.

Monitoring the annual variation of antibiotic resistance genes (ARGs) in livestock wastewater is important for determining the high-risk period of transfer and spread of animal-derived antibiotic resistance into the environment. However, the knowledge regarding the variation patterns of ARGs, especially intracellular ARGs (iARGs) and extracellular ARGs (eARGs), over time in livestock wastewater is still unclear. Herein, we conducted a year-round study to trace the profiles of ARGs at a Chinese-intensive dairy farm, focusing on the shifts observed in different months. The results showed significant differences in the composition and variation between iARGs and eARGs. Tetracycline, sulfonamide, and macrolide resistance genes were the major types of iARGs, while cfr was the major type of eARG. The environmental adaptations of the host bacteria determine whether ARGs appear as intracellular or extracellular forms. The total abundance of ARGs was higher from April to September, which can be attributed to the favorable climatic conditions for bacterial colonization and increased antibiotic administration during this period. Integron was found to be highly correlated with most iARGs, potentially playing a role in the presence of these genes within cells and their similar transmission patterns in wastewater. The intracellular and extracellular bacterial communities were significantly different, primarily because of variations in bacterial adaptability to the high salt and anaerobic environment. The intracellular co-occurrence network indicated that some dominant genera in wastewater, such as Turicibacter, Clostridium IV, Cloacibacillus, Subdivision5_genera_incertae_sedis, Saccharibacteria_genera_incertae_sedis and Halomonas, were potential hosts for many ARGs. To the best of our knowledge, this study demonstrates, for the first time, the annual variation of ARGs at critical points in the reuse of dairy farm wastewater. It also offers valuable insights into the prevention and control of ARGs derived from animals.

Green synthesis of CaxLa1-xMnO3 with modulation of mesoporous and vacancies for efficient low concentration phosphate adsorption.

Phosphate concentrations in eutrophic surface waters are usually low, and efficient removal of low concentration phosphate remains a challenge. In this study, Ca-doped LaMnO3 synthesized at doping ratios, designated as CaxLa1-xMnO3 (x = 0, 0.2, 0.4, 0.7), were compared. It was found that, the adsorption capacity of Ca0.4La0.6MnO3 material reached 63.01 mg/g at pH = 5, increased by 63.6% over the undoped LaMnO3 perovskite. For long-term adsorption, Ca0.4La0.6MnO3 could constantly adsorb phosphate to avoid phosphate accumulation (<0.05 mg/L). This proves that Ca0.4La0.6MnO3 has the ability to control dynamic water eutrophication. Characterization and density functional theory results confirmed that CaxLa1-xMnO3 can increase the content of mesopores and oxygen vacancies, providing additional active sites. This reduces the adsorption energy of the La site, promotes electron transfer, and increases its affinity. It provides a new method for removing low-concentration phosphates.

Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells.

Deubiquitinases (DUBs) play important roles in various human cancers and targeting DUBs is considered as a novel anticancer therapeutic strategy. Overexpression of ubiquitin specific protease 7 and 22 (USP7 and USP22) are associated with malignancy, therapy resistance, and poor prognosis in many cancers. Although both DUBs are involved in the regulation of similar genes and signaling pathways, such as histone H2B monoubiquitination (H2Bub1), c-Myc, FOXP3, and p53, the interdependence of USP22 and USP7 expression has never been described. In the study, we found that targeting USP7 via either siRNA-mediated knockdown or pharmaceutical inhibitors dramatically upregulates USP22 in cancer cells. Mechanistically, the elevated USP22 occurs through a transcriptional pathway, possibly due to desuppression of the transcriptional activity of SP1 via promoting its degradation upon USP7 inhibition. Importantly, increased USP22 expression leads to significant activation of downstream signal pathways including H2Bub1 and c-Myc, which may potentially enhance cancer malignancy and counteract the anticancer efficacy of USP7 inhibition. Importantly, targeting USP7 further suppresses the in vitro proliferation of USP22-knockout (USP22-Ko) A549 and H1299 lung cancer cells and induces a stronger activation of p53 tumor suppressor signaling pathway. In addition, USP22-Ko cancer cells are more sensitive to a combination of cisplatin and USP7 inhibitor. USP7 inhibitor treatment further suppresses in vivo angiogenesis and tumor growth and induced more apoptosis in USP22-Ko cancer xenografts. Taken together, our findings demonstrate that USP7 inhibition can dramatically upregulate USP22 in cancer cells; and targeting USP7 and USP22 may represent a more effective approach for targeted cancer therapy, which warrants further study. Video Abstract.

A phase 1 trial of fuzuloparib in combination with apatinib for advanced ovarian and triple-negative breast cancer: efficacy, safety, pharmacokinetics and germline BRCA mutation analysis.

BACKGROUND: The effect of the combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor in cancer treatment is unclear. We assessed the oral combination of fuzuloparib, a PARP inhibitor, and apatinib, a VEGFR2 inhibitor for treating advanced ovarian cancer (OC) or triple-negative breast cancer (TNBC). METHODS: This dose-escalation and pharmacokinetics-expansion phase 1 trial was conducted in China. We used a standard 3 + 3 dose-escalation design, with 7 dose levels tested. Patients received fuzuloparib orally twice daily, and apatinib orally once daily. The study objectives were to determine the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics, preliminary efficacy, and efficacy in relation to germline BRCA mutation (gBRCAmut). RESULTS: Fifty-two pre-treated patients were enrolled (30 OC/22 TNBC). 5 (9.6%) patients had complete response, 14 (26.9%) had partial response, and 15 (28.8%) had stable disease. Objective response rate (ORR) and disease control rate were 36.5% (95% CI 23.6-51.0) and 65.4% (95% CI 50.9-78.0), respectively. At the highest dose level of fuzuloparib 100 mg plus apatinib 500 mg, the ORR was 50.0% (4/8; 95% CI 15.7-84.3); this dose was determined to be the RP2D. Patients with gBRCAmut had higher ORR and longer median progression-free survival (PFS) than those with gBRCAwt, both in OC (ORR, 62.5% [5/8] vs 40.9% [9/22]; PFS, 9.4 vs 6.7 months) and TNBC (ORR, 66.7% [2/3] vs 15.8% [3/19]; PFS, 5.6 vs 2.8 months). Two dose-limiting toxicities occurred: grade 4 febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). Maximum tolerated dose was not reached. The most common treatment-related grade ≥ 3 toxicities in all patients were hypertension (19.2%), anaemia (13.5%), and decreased platelet count (5.8%). Exposure of apatinib increased proportionally with increasing dose ranging from 250 to 500 mg, when combined with fuzuloparib 100 mg. CONCLUSIONS: Fuzuloparib plus apatinib had acceptable safety in patients with advanced OC or TNBC. Fuzuloparib 100 mg bid plus apatinib 500 mg qd was established as the RP2D. With the promising clinical activity observed, this combination is warranted to be further explored as a potential alternative to chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03075462 (Mar. 9, 2017).

Efficacy and safety of PD-1 inhibitor combined with concurrent chemoradiotherapy in locally advanced cervical cancer with pelvic and/or para-aortic lymph node metastases: a retrospective cohort study.

BACKGROUND: The prognosis remains poor after standard chemoradiotherapy in locally advanced cervical cancer patients with pelvic and/or para-aortic lymph node metastases. Programmed cell death receptor-1 (PD-1) inhibitors have been recommended as the first-line treatment for recurrent cervical cancer. The efficacy of PD-1 inhibitor combined with concurrent chemoradiotherapy in locally advanced cervical cancer was still uncertain. This study aimed to explore the efficacy and safety of PD-1 inhibitors combined with concurrent chemoradiotherapy in locally advanced cervical cancer patients with pelvic and/or para-aortic lymph node metastases. METHODS: This retrospective study included patients with pelvic and/or para-aortic lymph node positive diseases [International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA] who had received PD-1 inhibitors plus chemoradiotherapy/radiotherapy between April 1, 2020, and March 31, 2022 at the Hunan Cancer Hospital. The baseline clinicopathological characteristics, treatment, and clinical outcomes were collected. The major clinical outcomes were objective response rate (ORR), progression-free survival (PFS), and treatment-related adverse events (TRAEs). RESULTS: A total of 29 patients were included. The mean age was 55.8 [standard deviation (SD): 8.8] years. Most patients had stage IIIA-IIIB disease (72.4%) and squamous cell carcinoma (93.1%). All patients had lymph node metastases, including 24 (82.8%) with multiple metastases and 11 (37.9%) with para-aortic lymph node metastases. Among the 29 patients, 18 received sintilimab and 11 received camrelizumab concurrently with chemoradiotherapy or radiotherapy. The ORR was 96.6% [95% confidence interval (CI): 0.828, 0.993] at 3 months after radiotherapy (including 15 complete responses and 13 partial responses). At the data cutoff (August 31, 2022), the median follow-up was 14 (range, 5-30) months. The median PFS was not mature. The estimated 1- and 2-year PFS rates were 85.3% (95% CI: 60.1%, 95.2%) and 76.8% (95% CI: 47.0%, 91.2%), respectively. TRAEs of any grade occurred in 27 (93.1%) patients, most commonly as a decrease in white blood counts (82.8%), anemia (58.6%), and fatigue (48.3%). TRAEs of grade 3 or greater occurred in eight (27.6%) patients. There were no treatment-related deaths. CONCLUSIONS: PD-1 inhibitor combined with concurrent chemoradiotherapy showed potential benefit in term of tumor response and PFS in locally advanced cervical cancer patients with pelvic and/or para-aortic lymph node metastases.

Phosphate adsorption on LDHs-biochar composite: Double-layer model for quantifying the contribution of ion exchange and ligand exchange.

The adsorption performance of layered double hydroxides (LDHs) is limited owing to self-aggregation. To avoid this and effectively control the eutrophication of water bodies, biochar (BC) was synthesized, herein, by pyrolyzing waste sheep manure at 500°C, and Ca-Al-LDHs were loaded on the surface via a coprecipitation method to obtain Ca-Al-LDHs-BC(CA) composites with varying LDH contents. The fitted maximum adsorption capacities of the CA-5%, CA-10%, CA-15%, and CA-20% samples (corresponding to samples with 5%, 10%, 15%, and 20% LDHs, respectively) were 10.21, 16.14, 22.40, and 28.47 mg g-1, which were (when converted into metal proportions) 1.48, 1.23, 1.15, and 1.13 times of that of single hydrotalcite, respectively. The double-layer model was fitted using the Levenberg-Marquardt iterative algorithm, which when combined with the characterization results, confirmed that the adsorption of phosphate ions by CA-BC occurred via the double-layer adsorption mechanism. Two types of direct adsorption were observed: ion exchange, which resulted in first-layer adsorption, and ligand exchange, which resulted in second-layer adsorption, with first-layer adsorption accounting for a higher proportion. This double-layer adsorption mechanism showed that LDHs-BC could achieve higher ligand exchange performance compared to that achieved using only LDHs.

Effects of soil habitat changes on antibiotic resistance genes and related microbiomes in paddy fields.

The changes of paddy soil habitat profoundly affect the structure and function of soil microorganisms, but how this process drives the growth and spread of manure- derived antibiotic resistance genes (ARGs) after entering the soil is unclear. Herein, this study explored the environmental fate and behavior of various ARGs in the paddy soil during rice growth period. Results showed that most ARG abundances in flooded soil was lower than that in non-flooded soil during rice growth (decreased by 33.4 %). And soil dry-wet alternation altered microbial community structure in paddy field (P < 0.05), showing that Actinobacteria and Firmicutes increased in proportion under non-flooded conditions, and Chloroflexi, Proteobacteria and Acidobacteria evolved into the dominant groups in flooded soil. Meanwhile, the correlation between ARGs and bacterial communities was stronger than that with mobile genetic elements (MGEs) in both flooded and non-flooded paddy soils. Furthermore, soil properties, especially oxidation reduction potential (ORP), were proved to be an essential factor in regulating the variability of ARGs in the whole rice growth stage by structural equation model, with a direct influence (λ = 0.38, P < 0.05), following by similar effects of bacterial communities and MGEs (λ = 0.36, P < 0.05; λ = 0.29, P < 0.05). This study demonstrated that soil dry-wet alternation effectively reduced the proliferation and dissemination of most ARGs in paddy fields, providing a novel agronomic measure for pollution control of antibiotic resistance in farmland ecosystem.

La-Ca/Fe-LDH-coupled electrochemical enhancement of organophosphorus removal in water: Organophosphorus oxidation improves removal efficiency.

Metal ions or metal (hydrogen) oxides are widely used as active sites in the construction of phosphate-adsorbing materials in water, but the removal of soluble organophosphorus from water remains technically difficult. Herein, synchronous organophosphorus oxidation and adsorption removal were achieved using electrochemically coupled metal-hydroxide nanomaterials. La-Ca/Fe-layered double hydroxide (LDH) composites prepared using the impregnation method removed both phytic acid (inositol hexaphosphate, IHP) and hydroxy ethylidene diphosphonic acid (HEDP) acid under an applied electric field. The solution properties and electrical parameters were optimized under the following conditions: organophosphorus solution pH = 7.0, organophosphorus concentration = 100 mg L-1, material dosage = 0.1 g, voltage = 15 V, and plate spacing = 0.3 cm. The electrochemically coupled LDH accelerates the removal of organophosphorus. The IHP and HEDP removal rates were 74.9% and 47%, respectively in only 20 min, 50% and 30% higher, respectively, than that of La-Ca/Fe-LDH alone. The removal rate in actual wastewater reached 98% in only 5 min. Meanwhile, the good magnetic properties of electrochemically coupled LDH allow easy separation. The LDH adsorbent was characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. It exhibits a stable structure under electric field conditions, and its adsorption mechanism mainly includes ion exchange, electrostatic attraction, and ligand exchange. This new approach for enhancing the adsorption capacity of LDH has broad application prospects in organophosphorus removal from water.

Implications of vermicompost on antibiotic resistance in tropical agricultural soils - A study in Hainan Island, China.

The contamination of antibiotic resistance genes (ARGs) associated with animal manure fertilization have attracted a global concern. Vermicompost has been widely popularized as an eco-friendly alternative to recycle animal manure on Hainan Island, China. However, the effects of vermicompost application on ARG spread and environmental fate in tropical agricultural soils remains undefined. Herein, the spatial prevalence and vertical behavior of ARGs in the soil profiles of vermicompost-applied agricultural regions were explored by a large-scale survey across Hainan Island. The results showed that although vermicompost application marginally enhanced the load of ARG pollution in the soil in Hainan, the ARGs derived from vermicompost did not eventually accumulate in the soil profile. The increase rate of ARGs in 40-60 cm soil layer was only 0.0015 % compared with that of unfertilized soil. Interestingly, vermicompost application reduced the abundance of high-risk ARGs, such as blaNDM and blaampC, by approximately one order of magnitude. Vermicompost was also observed to increase the abundance of beneficial bacteria, like Clostridium, and decrease those of Acidobacteriae, Planctomycetes and Verrucomicrobiae, which caused changes in the potential host bacteria of soil ARGs. Mobile genetic elements were further proven to be an essential factor that regulated the vertical dynamics of ARGs in vermicomposted soil, with a direct influence coefficient of 0.9975. This study demonstrated that the controllable risk associated with vermicompost application provided useful information to effectively reduce the threat of ARGs and promote the development of sustainable agriculture on Hainan Island.

Exploring antibiotic resistance load in paddy-upland rotation fields amended with commercial organic and chemical/slow release fertilizer.

Agricultural fertilization caused the dissemination of antibiotic resistance genes (ARGs) in agro-ecological environment, which poses a global threat to crop-food safety and human health. However, few studies are known about the influence of different agricultural fertilization modes on antibiotic resistome in the paddy-upland rotation soils. Therefore, we conducted a field experiment to compare the effect of different fertilization (chemical fertilizer, slow release fertilizer and commercial organic fertilizer replacement at various rates) on soil antibiotic resistome in paddy-upland rotation fields. Results revealed that a total of 100 ARG subtypes and 9 mobile genetic elements (MGEs) occurred in paddy-upland rotation soil, among which MDR-ARGs, MLSB-ARGs and tet-ARGs were the dominant resistance determinants. Long-term agricultural fertilization remarkably facilitated the vertical accumulation of ARGs, in particular that bla ampC and tetO in relative abundance showed significant enrichment with increasing depth. It's worth noting that slow release fertilizer significantly increased soil ARGs, when comparable to manure with 20% replacing amount, but chemical fertilizer had only slight impact on soil ARGs. Fertilization modes affected soil microbial communities, mainly concentrated in the surface layer, while the proportion of Proteobacteria with the highest abundance decreased gradually with increasing depth. Furthermore, microbial community and MGEs were further proved to be essential factors in regulating the variability of ARGs of different fertilization modes by structural equation model, and had strong direct influence (λ = 0.61, p < 0.05; λ = 0. 55, p < 0.01). The results provided scientific guidance for reducing the spreading risk of ARGs and control ARG dissemination in agricultural fertilization.