The photo-based treatment technology simultaneously removes resistant bacteria and resistant genes from wastewater.

Because of the recent widespread usage of antibiotics, the acquisition and dissemination of antibiotic-resistance genes (ARGs) were prevalent in the majority of habitats. Generally, the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria (ARB) disinfection and ARGs degradation and even promote the proliferation of ARGs. Problematically, ARB and ARGs in effluent pose potential risks if they are not further treated. Photocatalytic oxidation is considered a promising disinfection technology, where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid (DNA) for ARB elimination and subsequent degradation of ARGs. This review aims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant (AR) from wastewater in recent years. We discuss the sources and transfer of ARGs in wastewater. The overall removal efficiencies of ultraviolet radiation (UV)/chlorination, UV/ozone, UV/H2O2, and UV/sulfate-radical based system for ARB and ARGs, as well as the experimental parameters and removal mechanisms, are systematically discussed. The contribution of photocatalytic materials based on TiO2 and g-C3N4 to the inactivation of ARB and degradation of ARGs is highlighted, producing many free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer (HGT) in wastewater. Finally, based on the reviewed studies, future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.

Seasonal and interannual variations of nutrients in the Subei Shoal and their implication for the world's largest green tide.

The world's largest "green tide" (Ulva prolifera) has occurred every year since 2007 in the Yellow Sea. The Subei Shoal area is thought to be the origin of the green tide. Based on field data from 2016 to 2023, seasonal and interannual variations of dissolved nutrients and their ecological effects in the Subei Shoal were analyzed. Spatial distribution of dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP) and dissolved silicate (DSi) showed clear terrestrial sources, while ammonia (NH4-N) and dissolved organic nitrogen (DON) were not solely controlled by terrestrial sources. The seasonal variations of NH4-N, DIN, DON, DIP and DSi concentrations were significant, and the interannual variations of DIN, DON, DIP and DSi concentrations showed general decreasing trends from 2016 to 2023. The key factors affecting the seasonal and interannual variations of DIN and DIP concentrations were terrestrial input, aquaculture wastewater discharge, atmospheric deposition, submarine groundwater discharge and macroalgae absorption, while the dominant factor determining the variations of DSi concentrations was terrestrial input. NH4-N and DON concentrations were mainly influenced by aquaculture wastewater discharge and the absorption and release of macroalgae. The high nutrient concentrations in the Subei Shoal throughout the year provided sufficient material basis for the growth of Ulva prolifera in the source area of green tide outbreak.

Spin-Charge Conversion in Chiral Polymers with Hopping Conduction.

Organic and biological materials are often chiral. Chiral polymers, as recent experiments indicate, facilitate spin-charge conversion: a charge current results in a spin polarization and vice versa, dubbed chirality-induced spin selectivity (CISS) and inverse CISS (ICISS). While CISS/ICISS in crystalline chiral systems such as tellurium can be understood in terms of their chirality- and spin-dependent band structure, such a picture becomes inapplicable to disordered chiral polymers, where carrier transport is via hopping rather than band conduction. Here, we develop a microscopic theory to describe CISS and ICISS in disordered chiral organics, in which chirality-induced geometric spin-orbit coupling leads to a purely geometric spin-dependent Berry phase in electron hops involving triads, whose orientations are dictated by the material's chirality. Our theory reveals a central role of spin-flip hopping, which suppresses CISS but enables ICISS.

VASE: A High-Entropy Alloy Short-Range Order Structural Descriptor for Machine Learning.

The short-range order (SRO) structure in high-entropy alloys (HEAs) is closely associated with many properties, which can be studied through density functional theory (DFT) calculations. Atomic-scale modeling and calculations require substantial computational resources, and machine learning can provide rapid estimations of DFT results. To describe SRO information in HEAs, a new descriptor based on Voronoi Analysis and Shannon Entropy (VASE) is proposed. Based on Voronoi analysis, the Shannon entropy is introduced to directly characterize atomic spatial arrangement information except for composition and atomic interactions, which is necessary for describing the disorder atomic occupancy in HEAs. The new descriptor is used for predicting the formation energy of FeCoNiAlTiCu system based on machine learning model, which is more accurate than other descriptors (Coulomb matrices, partial radial distribution functions, and Voronoi analysis). Moreover, the model trained based on VASE descriptors exhibits the best predictive performance for unrelaxed structures (24.06 meV/atom). The introduction of Shannon entropy provides an effective representation of atomic arrangement information in HEAs, which is a powerful tool for investigating the SRO phenomena.

Periductal Mastitis, a Disease with Distinct Clinicopathological Features from Granulomatous Lobular Mastitis.

Purpose: Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies. Patients and Methods: Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration. Results: PDM patients had a higher median age compared to GLM patients (38 vs 32, p<0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p<0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p<0.001), ductal wall thickening (47.93% vs 1.75%, p<0.001), and ductal rupture (44.63% vs 5.26%, p<0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p<0.001), microabscess (68.42% vs 28.93%, p<0.001), and lipid vacuole (40.35% vs 8.26%, p<0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy. Conclusion: PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.

Study on the photo/electrochemical bi-functional properties of a coupling interface of Ru[dcbpy]32+-AMT/Au by SECM imaging-based joint analytical method.

A photo/electrochemical coupling interface of Ru[dcbpy]32+-AMT/Au (AMT; 5-Amino-1,3,4-thiadiazole-2-thiol) was fabricated using a dehydration condensation sulfhydrating method. For the interface functional properties, a combined dual-signal recording (CDSR) method was applied to characterize the response characteristics, and a scanning electrochemical microscopy-electrochemiluminescence (SECM-ECL) imaging was developed to assess the interface distribution uniformity. The interface biosensing compatibility was validated by constructing a simple DNA sensor. The research results show that the interaction between the two functional parameters follows a synergistic effect mechanism in the coupling conditions and an interference effect mechanism in the detection condition. Under optimized conditions, the saturation dual-signal response values are 156.0 and 86.8 µA, respectively. The statistics and imaging comparison analysis validate good interface distribution uniformity and stability performance. The DNA sensor's dual-signal detection limits to the signal probe (SP) are ∼30 fM and 0.3 pM with linear ranges of 100.0 fM âˆ¼ 1.0 nM and 1.0 pM âˆ¼ 10.0 nM, respectively. The fabricated interface exhibits an effective bi-functional response performance compatible with biosensing. The proposed imaging method has a high technical fit for studying photo/electrochemical coupling interfaces and can also provide a reference for other similar coupling interface analyses.

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.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. Methods: The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. Results: In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. Conclusion: We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

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.

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.

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.

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.