Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors.

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown. Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab. Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model. Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Label-free Raman spectroscopy reveals tumor microenvironmental changes induced by intermittent fasting for the prevention of breast cancer in animal model.

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines. Raman measurements revealed remarkable and robust differences in lipid, protein, and glycogen content prior to morphological manifestations in a dynamically changing tumor microenvironment, consistent with the proteomic changes observed by quantitative mass spectrometry. Taken together with its non-invasive nature, this research provides prospective evidence for the clinical translation of Raman spectroscopy to identify biomolecular variations in the microenvironment induced by intermittent fasting for the prevention of breast cancer, providing new perspectives on the specific molecular effects in the tumorigenesis of breast cancer.

Distribution patterns and origins of organophosphate esters in soils from different climate systems on the Tibetan Plateau.

Organophosphate esters (OPEs) are extensively applied in various materials as flame retardants and plasticizers, and have high biological toxicity. OPEs are detected worldwide, even in distant polar regions and the Tibetan Plateau (TP). However, few studies have been performed to evaluate the distribution patterns and origins of OPEs in different climate systems on the TP. This study investigated the distribution characteristics, possible sources, and ecological risks of OPEs in soils from the different climate systems on the TP and its surroundings. The total concentrations of OPEs in soil varied from 468 to 17,451 pg g-1 dry weight, with greater concentrations in southeast Tibet (monsoon zone), followed by Qinghai (transition zone) and, finally, southern Xingjiang (westerly zone). OPE composition profiles also differed among the three areas with tri-n-butyl phosphate dominant in the westerly zone and tris(2-butoxyethyl) phosphate dominant in the Indian monsoon zone. Correlations between different compounds and altitude, soil organic carbon, or longitude varied in different climate zones, indicating that OPE distribution originates from both long-range atmospheric transport and local emissions. Ecological risk assessment showed that tris(2-chloroethyl) phosphate and tri-phenyl phosphate exhibited medium risks in soil at several sites in southeast Tibet. Considering the sensitivity and vulnerability of TP ecosystems to anthropogenic pollutants, the ecological risks potentially caused by OPEs in this region should be further assessed.

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta­analysis of eight short­term, randomized, double­blind, placebo­controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

Inverse chirality-induced spin selectivity effect in chiral assemblies of π-conjugated polymers.

Coupling of spin and charge currents to structural chirality in non-magnetic materials, known as chirality-induced spin selectivity, is promising for application in spintronic devices at room temperature. Although the chirality-induced spin selectivity effect has been identified in various chiral materials, its Onsager reciprocal process, the inverse chirality-induced spin selectivity effect, remains unexplored. Here we report the observation of the inverse chirality-induced spin selectivity effect in chiral assemblies of π-conjugated polymers. Using spin-pumping techniques, the inverse chirality-induced spin selectivity effect enables quantification of the magnitude of the longitudinal spin-to-charge conversion driven by chirality-induced spin selectivity in different chiral polymers. By widely tuning conductivities and supramolecular chiral structures via a printing method, we found a very long spin relaxation time of up to several nanoseconds parallel to the chiral axis. Our demonstration of the inverse chirality-induced spin selectivity effect suggests possibilities for elucidating the puzzling interplay between spin and chirality, and opens a route for spintronic applications using printable chiral assemblies.

Detoxification of copper and zinc from anaerobic digestate effluent by indigenous bacteria: Mechanisms, pathways and metagenomic analysis.

The presence of organic-complexed copper and zinc in anaerobic digestate effluent (ADE) poses persistent ecological toxicity. This study investigated the detoxification performance and biotic responses of indigenous bacteria against ethylene diamine tetraacetic acid (EDTA)-complexed Cu(II) and Zn(II). Heavy metals (HMs) stress induced reactive oxygen species (ROS) generation and enhanced extracellular polymeric substances (EPS) secretion. At a Cu(II) influent concentration of 20.0 mg·L-1, indigenous bacteria removed 88.2% of Cu(II) within nine days. The majority of copper and zinc sequestered by bacteria were stored in the cell envelope, with over 50% of copper and 60% of zinc being immobilized. Transmission electron microscopy mapping (TEM-mapping) revealed significant mineralization of copper and zinc on the cell wall. Proteins abundant in EPS, alongside humic acid-like substances, effectively adsorbed HMs. Indigenous bacteria exhibited the capacity to reduce cupric to the cuprous state and cupric is preferentially reduced to cuprous before reaching reducing capacity saturation. Sulfur precipitation emerges as a crucial pathway for Zn(II) removal. Metagenomic analysis indicated that indigenous bacteria upregulated genes related to HMs homeostasis, efflux, and DNA repair, enhancing its resistance to high concentrations HMs. This study provided theoretical guidance for employing bacterial consortia to eliminate HMs in complex aquatic environments.

Elimination of copper obstacle factor in anaerobic digestion effluent for value-added utilization: Performance and resistance mechanisms of indigenous bacterial consortium.

The presence of excessive residual Cu(II), a high-risk heavy metal with potential toxicity and biomagnification property, substantially impede the value-added utilization of anaerobic digestion effluent (ADE). This study adapted indigenous bacterial consortium (IBCs) to eliminate Cu(II) from ADE, and their performances and resistance mechanisms against Cu(II) were analyzed. Results demonstrated that when the Cu(II) exposure concentration exceeded 7.5 mg/L, the biomass of IBCs decreased significantly, cells produced a substantial amount of ROS and EPS, at which time the intracellular Cu(II) content gradually decreased, while Cu(II) accumulation within the EPS substantially increased. The combined features of a high PN/PS ratio, a reversed Zeta potential gradient, and abundant functional groups within EPS collectively render EPS a primary diffusion barrier against Cu(II) toxicity. Mutual physiological and metagenomics analyses reveal that EPS synthesis and secretion, efflux, DNA repair along with coordination between each other were the primary resistance mechanisms of IBCs against Cu(II) toxicity. Furthermore, IBCs exhibited enhanced resistance by enriching bacteria carrying relevant resistance genes. Continuous pretreatment of actual ADE with IBCs at a 10-day hydraulic retention time (HRT) efficiently eliminated Cu(II) concentration from 5.01 mg/L to ∼0.68 mg/L by day 2. This elimination remained stable for the following 8 days of operation, further validated their good Cu(II) elimination stability. Notably, supplementing IBCs with 200 mg/L polymerized ferrous sulfate significantly enhanced their settling performance. By elucidating the intricate interplay of Cu(II) toxicity and IBC resistance mechanisms, this study provides a theoretical foundation for eliminating heavy metal barriers in ADE treatment.

An advanced machine learning method for simultaneous breast cancer risk prediction and risk ranking in Chinese population: A prospective cohort and modeling study.

BACKGROUND: Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors. METHODS: The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020. RESULTS: The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy. CONCLUSIONS: We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Facet impact of CeO2@C 2D core-shell structure on electrochemical reaction kinetic factor and efficient detection of nitrite.

Fine-tuning the surface structure of transition metal oxides at the atomic level is a promising way to improve the catalytic properties of materials. However, the influence of crystal surface structure on electrode reaction kinetics is still limited. In this study, we propose an in-situ synthesis strategy to obtain two-dimensional carbon/cerium oxide core-shell nanosheets by thermal decomposition of Ce-MOF nanosheets grown on the surface of carbon nanostructures, and fine-tuning the surface structure by introducing oxygen vacancies through defect engineering during the oxide nucleation process is conducted to obtain controllable exposed {111} and {110} surface CeO2@C composites. Both experiments and theoretical calculations show that the {110} -dominated nanocomplex (CeO2@C-350S) has better kinetic behavior and catalytic activity due to its abundant surface defects, which is manifested in higher active surface area, richer carrier concentration, and better promotion of diffusion and adsorption. In addition, CeO2@C-350S electrode has an extremely wide linear range and good stability in the electrochemical detection of nitrite. After 1000 times of the accelerated cycle experiments, CeO2@C-350S electrode still maintains 79.3 % of its initial current response, and recovers to 87.3 % after 10 min of stopping the test. The electrode stability is excellent, which is attributed to the clever carbon shell structure of the material. This synthesis strategy can be extended to other carbon-based oxide composite catalysts to improve the electrocatalytic performance and overall stability by adjusting the surface structure.

Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. METHODS: We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. RESULTS: The most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. CONCLUSIONS: Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1P409L, ADGRA2 and ADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

Effects of seasonal deposition-erosion cycle on sedimentary organic carbon remineralization and oxygen consumption in a large-river delta-front estuary.

Seasonal sediment deposition-erosion events are dominant drivers of particle-solute dynamics in large-river delta-front estuaries (LDEs), but their influence on elemental cycles is not yet fully understood. To better constrain the role of deposition-erosion events on elemental cycling in LDEs, benthic fluxes of dissolved inorganic carbon (DIC), oxygen, and pore-water solute profiles were measured over different seasons in the Changjiang LDE. Benthic DIC efflux (23.4 ± 6.0 mmol C m-2 d-1) was greater than oxygen influx (7.5 ± 2.0 mmol O2 m-2 d-1) in summer but less in winter (7.7 ± 1.2 mmol C m-2 d-1 and 10.1 ± 1.5 mmol O2 m-2 d-1, respectively). The additional oxygen consumption in sediments in winter was likely due to the oxidation of inorganic diagenetic reductive products (IDRP) (e.g., NH4+, Fe2+, and Mn2+) in deeper sediments exposed by erosion, which resulted in the development of an "oxygen debt". Sedimentary oxygen respiration accounted for at least 48 % of total oxygen consumption (oxygen consumption in both water column and sediment) in winter and was significantly greater than in summer (∼15 %); this highlighted the importance of winter sediment erosion in oxygen depletion. In addition to IDRP oxidation, the remineralization of resuspended sedimentary organic carbon in water column also contributed to the oxygen consumption. The global dataset on benthic DIC and oxygen fluxes provides evidence that the "oxygen debt" is likely to be widespread in LDEs, exerting a significant impact on global carbon and oxygen cycling.

Axillary lymph node dissection in triple-negative or HER2-positive breast cancer patients with clinical N2 achieving pathological complete response after neoadjuvant therapy: Is it necessary?

AIM: This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）. BACKGROUND: Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery. METHODS: A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined. RESULTS: Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1-19.1), compared to those who did achieve breast pCR, P < 0.001. CONCLUSION: For cN2 TN or HER2+ breast cancer patients who achieve breast pCR following NAT, consideration could be given to downstaging and performing an axillary SLNB or TAD.

Environmental surveillance in Jinan city of East China (2014-2022) reveals improved air quality but remained health risks attributable to PM2.5-bound metal contaminants.

PM2.5-bound metal contaminants are associated with multiple chronic diseases in human. At global level, the contamination status has not been well controlled yet. Here we report findings from a long-term air pollution surveillance in Jinan city of Shandong, China. During 2014-2022, the dynamics and trends of PM2.5-bound heavy metal contaminants were monitored in an industrial area and a downtown area. The surveillance targets included: antimony (Sb), aluminum (Al), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), manganese (Mn), nickel (Ni), selenium (Se). The human exposure and health risks were calculated and we found that the health risks of most contaminants showed peak values in autumn and winter. But Al, Mn, Hg and Be were found to result in highest health risk in spring or summer in the downtown area. In the industrial area we identified 100% alarming health index >1 (ranged from 1.12 to 3.35) in autumn and winter. In winter the total non-carcinogenic HI was all above 1 (peak value 2.21). Mn and As together posed >85% non-carcinogenic risk. As and Cd were ranked as major drivers of carcinogenic risks (5.84 × 10-6 and 2.78 × 10-6). Pd and Cd both showed non-negligible environmental levels but risk assessment model for their air-exposure associated non-carcinogenic risks are not yet available. This study updates air pollution data and status for air pollution status in China. This study provides valuable 9 year long-term reference to experimental and field studies in the related fields.

Size-fractionated distribution of glycerol dialkyl glycerol tetraether core lipids in surface sediments of a large-river delta-front estuary.

Glycerol dialkyl glycerol tetraether core lipids (GDGTs) are microbial biomarkers ubiquitously distributed in terrestrial and marine environments. Dispersal and fate of GDGTs in an estuary largely depends on sediment grain size, however, their size distribution patterns remain poorly understood. Here, surface sediments collected from the Changjiang Estuary were separated into <20, 20-32, 32-63, 63-125 and >125 µm fractions, and analyzed for GDGTs as well as total organic carbon (TOC), stable isotopic composition (δ13C) of TOC and lignin phenols, to investigate the size and spatial distributions of GDGTs and the particle size effects on GDGTs proxies in this large river delta-front estuary. The concentrations of isoprenoidal GDGTs (isoGDGTs) were higher in the finest fractions and in off-estuary sites. On the contrary, branched GDGTs (brGDGTs) were high not only in the finest fractions but in coarser fractions (>32 µm fractions), and thus at both near- and off-estuary sites. The branched and isoprenoid tetraether (BIT) index increased with increasing grain size, and decreased sharply from the estuary (~0.52) to the shelf (~0.16). BrGDGTs were positively correlated with crenarcheaol in both high and low BIT regions. The brGDGTIIIa/IIa ratios in all size fractions were <0.59, further indicating that the brGDGTs were mainly derived from terrestrial input with minimum in-situ production. Fractional TOC source assignments derived from the BIT index was significantly positively correlated with the fractions of terrestrial OC from a mixing model based on δ13C-TOC and lignin contents, indicating that BIT may track a broader pool of terrestrial OC than just soil OC. This work provides novel, yet preliminary insights into the size fractionated distribution characteristics of GDGTs and the applicability of BIT as a proxy for OC sources in estuarine sediments. More work is needed to further clarify the particle size effects on other GDGTs proxies in estuarine systems.

Efficacy and safety of rifampicin-based triple therapy for non-puerperal mastitis: A single-arm, open-label, prospective clinical trial.

OBJECTIVES: To assess the efficacy and safety of rifampicin-based triple therapy (rifampicin, isoniazid, and ethambutol) for treating NPM. METHODS: This single-center, single-arm, prospective clinical trial was conducted at the Second Hospital of Shandong University (Jinan, China). Patients with pathologically diagnosed granulomatous lobular mastitis and periductal mastitis received triple drugs, i.e., rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (15 mg/kg/day), until complete response or the investigator decided to discontinue treatment. The primary endpoint was the complete response rate (CRR) assessed by the investigator. The secondary endpoints included the overall remission rate (ORR), recurrence rate (RR), and safety. RESULTS: A total of 218 patients were enrolled in the study between January 1, 2013 and October 31, 2020. With a median follow-up time of 48 months, the CRR and the ORR were 78.44% and 94.04%, respectively. While 13 patients (5.96%) demonstrated no response and 19 relapsed (8.72%). Adverse events (AEs) were not common. The most common AEs during treatment were liver dysfunction (1.83%), gastrointestinal reactions (1.83%), fatigue (1.83%), erythema (1.38%), and menstrual disorders (0.92%). CONCLUSION: Rifampicin, isoniazid, and ethambutol demonstrated promising response rates with acceptable safety profiles in patients with NPM. Further confirmatory trial is warranted in the future. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the Second Hospital of Shandong University and retrospectively registered at the China Clinical Trial Registration Center (registration number: ChiCTR2100049591).

Microbial community function and methylmercury production in oxygen-limited paddy soil.

Methylmercury is a neurotoxic compound that can enter rice fields through rainfall or irrigation with contaminated wastewater, and then contaminate the human food chain through the consumption of rice. Flooded paddy soil has a porous structure that facilitates air exchange with the atmosphere, but the presence of trace amounts of oxygen in flooded rice field soil and its impact on microbial-mediated formation of methylmercury is still unclear. We compared the microbial communities and their functions in oxygen-depleted and oxygen-limited paddy soil. We discovered that oxygen-limited paddy soil had higher methylmercury concentration, which was strongly correlated with soil properties and methylation potential. Compared with oxygen-depleted soil, oxygen-limited soil altered the microbial composition based on 16 S rRNA sequences, but not based on hgcA sequences. Moreover, oxygen-limited soil enhanced microbial activity significantly, increasing the abundance of more than half of the KEGG pathways, especially the metabolic pathways that might be involved in methylation. Our study unveils how microbial communities influence methylmercury formation in oxygen-limited paddy soil. ENVIRONMENTAL IMPLICATIONS: This study examined how low oxygen input affects microbial-induced MeHg formation in anaerobic paddy soil. We found that oxygen-limited soil produced more MeHg than oxygen-depleted soil. Oxygen input altered the microbial community structure of 16 S rRNA sequencing in anaerobic paddy soil, but had little impact on the hgcA sequencing community structure. Microbial activity and metabolic functions related to MeHg formation were also higher in oxygen-limited paddy soil. We suggest that oxygen may not be a limiting factor for Hg methylators, and that insufficient oxygen input in flooded paddy soil increases the risk of human exposure to MeHg from rice consumption.

Erratum: [Corrigendum] Mesenchymal stem cells expressing interleukin­18 suppress breast cancer cells in vitro.

[This corrects the article DOI: 10.3892/etm.2015.2286.].

Nitrogen from agriculture and temperature as the major drivers of deoxygenation in the central Bohai Sea.

Agricultural N losses strongly dominate the N delivery (average 72 % of total N delivery to rivers in the period 1980-2010) in the rivers discharging into the Bohai Sea, a semi-enclosed marginal sea, which has been suffering from eutrophication and deoxygenation since the 1980s. In this paper we investigate the relationship between N loading and deoxygenation in the Bohai Sea, and consequences of future N loading scenarios. Using modeling for the period 1980-2010, the contributions of different oxygen consumption processes were quantified and the main controlling mechanisms of summer bottom dissolved oxygen (DO) evolution in the central Bohai Sea were determined. Model results show that the water column stratification during summer impeded the DO exchange between oxygenated surface water and oxygen-poor bottom water. Water column oxygen consumption (60 % of total oxygen consumption) was strongly correlated with elevated nutrient loading, while nutrient imbalances (increasing N:P ratios) enhanced harmful algal bloom proliferation. Future scenarios show that deoxygenation may be reduced in all scenarios owing to increasing agricultural efficiency, manure recycling and wastewater treatment. However, even in the sustainable development scenario SSP1, nutrient discharges in 2050 will still exceed the 1980 levels, and with further enhancement of water stratification due to climate warming, the risk of summer hypoxia in bottom waters may persist in the coming decades.