A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

Research and experimental verification on the mechanisms of cellular senescence in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high heterogeneity, poor prognosis, and a low 10-year survival rate of less than 50%. Although cellular senescence displays extensive effects on cancer, the comprehensions of cellular senescence-related characteristics in TNBC patients remains obscure. Method: Single-cell RNA sequencing (scRNA-seq) data were analyzed by Seurat package. Scores for cellular senescence-related pathways were computed by single-sample gene set enrichment analysis (ssGSEA). Subsequently, unsupervised consensus clustering was performed for molecular cluster identification. Immune scores of patients in The Cancer Genome Atlas (TCGA) dataset and associated immune cell scores were calculated using Estimation of STromal and Immune cells in MAlignantTumours using Expression data (ESTIMATE) and Microenvironment Cell Populations-counter (MCP-counter), Tumor Immune Estimation Resource (TIMER) and Estimating the Proportion of Immune and Cancer cells (EPIC) methods, respectively. Immunotherapy scores were assessed using TIDE. Furthermore, feature genes were identified by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses; these were used to construct a risk model. Additionally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and transwell assay were conducted for in vitro validation of hub genes. Result: TNBC was classified into three subtypes based on cellular senescence-related pathways as clusters 1, 2, and 3. Specifically, cluster 1 showed the best prognosis, followed by cluster 2 and cluster 3. The levels of gene expression in cluster 2 were the lowest, whereas these were the highest in cluster 3. Moreover, clusters 1 and 3 showed a high degree of immune infiltration. TIDE scores were higher for cluster 3, suggesting that immune escape was more likely in patients with the cluster 3 subtype who were less likely to benefit from immunotherapy. Next, the TNBC risk model was constructed and validated. RT-qPCR revealed that prognostic risk genes (MMP28, ACP5 and KRT6A) were up-regulated while protective genes (CT83) were down-regulated in TNBC cell lines, validating the results of the bioinformatics analysis. Meanwhile, cellular experiments revealed that ACP5 could promote the migration and invasion abilities in two TNBC cell lines. Finally, we evaluated the validity of prognostic models for assessing TME characteristics and TNBC chemotherapy response. Conclusion: In conclusion, these findings help to assess the efficacy of targeted therapies in patients with different molecular subtypes, have practical applications for subtype-specific treatment of TNBC patients, and provide information on prognostic factors, as well as guidance for the revelation of the molecular mechanisms by which senescence-associated genes influence TNBC progression.

Protein Identification and Quantification Using Porous Silicon Arrays, Optical Measurements, and Machine Learning.

We report a versatile platform based on an array of porous silicon (PSi) thin films that can identify analytes based on their physical and chemical properties without the use of specific capture agents. The ability of this system to reproducibly classify, quantify, and discriminate three proteins separately is demonstrated by probing the reflectance of PSi array elements with a unique combination of pore size and buffer pH, and by analyzing the optical signals using machine learning. Protein identification and discrimination are reported over a concentration range of two orders of magnitude. This work represents a significant first step towards a low-cost, simple, versatile, and robust sensor platform that is able to detect biomolecules without the added expense and limitations of using capture agents.

Tunable electrical properties and multiple-phases of ferromagnetic GdS2, GdSe2 and Janus GdSSe monolayers.

With the continuous miniaturization and integration of spintronic devices, the two-dimensional (2D) ferromagnet coupling of ferromagnetic and diverse electrical properties has become increasingly important. Herein, we report three ferromagnetic monolayers: GdS2, GdSe2 and Janus GdSSe. They are bipolar magnetic semiconductors and demonstrate ferroelasticity with a large reversible strain of 73.2%. Three monolayers all hold large magnetic moments of about 8µB f.u.-1 and large spin-flip energy gaps in both the conduction and valence bands, which are highly desirable for applications in bipolar field effect spin filters and spin valves. Our calculations have testified to the feasibility of the experimental achievement of the three monolayers and their stability. Additionally, intrinsic valley polarization occurs in the three monolayers owing to the cooperative interplay between spin-orbit coupling and magnetic exchange interaction. Moreover, we identified square lattices for GdS2 and GdSe2 monolayers. The new and stable square lattices of GdS2 and GdSe2 monolayers show robust ferromagnetism with high Curie temperatures of 648 and 312 K, respectively, and the characteristics of spin-gapless semiconductors. Overall, these findings render GdS2, GdSe2 and Janus GdSSe monolayers promising candidate materials for multifunctional spintronic devices at the nanoscale.

Two-dimensional MN4 materials as effective multifunctional electrocatalysts for the hydrogen-evolution, oxygen-evolution, and oxygen-reduction reactions.

Two-dimensional (2D) materials confining single atoms (SAs) for catalysis, such as graphene confining metal single atoms (M-N-C), integrate both aspects of 2D materials and single-atom catalysts (SACs). Significant advantages have been established in this new category of catalysts, which have seen rapid development in recent years. Recent studies have suggested a new class of novel 2D materials with a chemical formula of MN4 naturally holding a uniformly distributed M-N4 moiety. We investigated MN4 monolayers as multifunctional catalysts for the hydrogen-evolution reaction (HER), oxygen-evolution reaction (OER), and oxygen-reduction reaction (ORR). Among them, the IrN4 monolayer demonstrated high catalytic activity towards these three reactions. The CoN4 monolayer was predicted to be an excellent bifunctional catalyst for the OER and ORR. A uniformly distributed and short-distanced M-N4 moiety on the MN4 monolayer made reactions between the intermediates during the OER and ORR possible, facilitating the release of O2 and H2O, respectively. In addition, the M atom of the MN4 monolayer having electronic states located at the Fermi level was active for catalyzing the HER. More importantly, changes in the Gibbs free energy of the two key intermediates of adsorption (ΔGOH* and ΔGOOH*) correlated closely with the Bader charge on the M atom (BM).

Switchable Anomalous Hall Effects in Polar-Stacked 2D Antiferromagnet MnBi2Te4.

van der Waals (vdW) assembly of two-dimensional (2D) materials allows polar layer stacking to realize novel properties switchable by the induced electric polarization. Here, based on symmetry analyses and density-functional calculations, we explore the emergence of the anomalous Hall effect (AHE) in antiferromagnetic MnBi2Te4 films assembled by polar layer stacking. We demonstrate that breaking P̂T̂ symmetry in an MnBi2Te4 bilayer produces a magnetoelectric effect and a spontaneous AHE switchable by electric polarization. We find that reversible polarization at one of the interfaces in a three-layer MnBi2Te4 film drives a metal-insulator transition, as well as switching between the AHE and quantum AHE (QAHE). Finally, we predict that engineering interlayer polarization in a three-layer MnBi2Te4 film allows converting MnBi2Te4 from a trivial insulator to a Chern insulator. Overall, our work emphasizes the topological properties in 2D vdW antiferromagnets induced by polar layer stacking, which do not exist in a bulk material.

Interface-engineered ferroelectricity of epitaxial Hf0.5Zr0.5O2 thin films.

Ferroelectric hafnia-based thin films have attracted intense attention due to their compatibility with complementary metal-oxide-semiconductor technology. However, the ferroelectric orthorhombic phase is thermodynamically metastable. Various efforts have been made to stabilize the ferroelectric orthorhombic phase of hafnia-based films such as controlling the growth kinetics and mechanical confinement. Here, we demonstrate a key interface engineering strategy to stabilize and enhance the ferroelectric orthorhombic phase of the Hf0.5Zr0.5O2 thin film by deliberately controlling the termination of the bottom La0.67Sr0.33MnO3 layer. We find that the Hf0.5Zr0.5O2 films on the MnO2-terminated La0.67Sr0.33MnO3 have more ferroelectric orthorhombic phase than those on the LaSrO-terminated La0.67Sr0.33MnO3, while with no wake-up effect. Even though the Hf0.5Zr0.5O2 thickness is as thin as 1.5 nm, the clear ferroelectric orthorhombic (111) orientation is observed on the MnO2 termination. Our transmission electron microscopy characterization and theoretical modelling reveal that reconstruction at the Hf0.5Zr0.5O2/ La0.67Sr0.33MnO3 interface and hole doping of the Hf0.5Zr0.5O2 layer resulting from the MnO2 interface termination are responsible for the stabilization of the metastable ferroelectric phase of Hf0.5Zr0.5O2. We anticipate that these results will inspire further studies of interface-engineered hafnia-based systems.

CO2 coverage on Pd catalysts accelerates oxygen removal in oxy-combustion systems.

Oxy-combustion systems result in enriched CO2 in exhaust gases; however, the utilization of the concentrated CO2 stream from oxy-combustion is limited by remnant O2. CH4 oxidation using Pd catalysts has been found to have high O2-removal efficiency. Here, the effect of excess CO2 in the feed stream on O2 removal with CH4 oxidation is investigated by combining experimental and theoretical approaches. Experimental results reveal complete CH4 oxidation without any side-products, and a monotonic increase in the rate of CO2 generation with an increase in CO2 concentration in the feed stream. Density-functional theory calculations show that high surface coverage of CO2 on Pd leads to a reduction in the activation energy for the initial dissociation of CH4 into CH3 and H, and also the subsequent oxidation reactions. A CO2-rich environment in oxy-combustion systems is therefore beneficial for the reduction of oxygen in exhaust gases.

Cu-doped SnS2 nanosheets with superior visible-light photocatalytic CO2 reduction performance.

Photocatalytic CO2 reduction utilizing solar energy is a clean, environment-friendly strategy converting CO2 into hydrocarbon fuels to solve the energy crisis and climate issues. Herein, we report the synthesis of Cu-doped SnS2 nanosheets via a simple hydrothermal method. The prepared Cu-doped SnS2 composite displays superior photocatalytic CO2 reduction activity. The optimized CH3OH yield of the composite is two times higher than that of pure SnS2. The enhanced photocatalytic performance is attributed to effective charge separation resulting from the thinner nanosheets and delocalization of electrons from SnS2 to Cu, high visible light utilization efficiency, enlarged SBET, negative shift of the flat-band potential and reduced charge transfer resistance with the introduction of Cu atoms. This work suggests the potential application of Cu-doped SnS2 in photocatalytic CO2 reduction.

Spontaneous Seed Formation during Electrodeposition Drives Epitaxial Growth of Metastable Bismuth Selenide Microcrystals.

Materials with metastable phases can exhibit vastly different properties from their thermodynamically favored counterparts. Methods to synthesize metastable phases without the need for high-temperature or high-pressure conditions would facilitate their widespread use. We report on the electrochemical growth of microcrystals of bismuth selenide, Bi2Se3, in the metastable orthorhombic phase at room temperature in aqueous solution. Rather than direct epitaxy with the growth substrate, the spontaneous formation of a seed layer containing nanocrystals of cubic BiSe enforces the metastable phase. We first used single-crystal silicon substrates with a range of resistivities and different orientations to identify the conditions needed to produce the metastable phase. When the applied potential during electrochemical growth is positive of the reduction potential of Bi3+, an initial, Bi-rich seed layer forms. Electron microscopy imaging and diffraction reveal that the seed layer consists of nanocrystals of cubic BiSe embedded within an amorphous matrix of Bi and Se. Using density functional theory calculations, we show that epitaxial matching between cubic BiSe and orthorhombic Bi2Se3 can help stabilize the metastable orthorhombic phase over the thermodynamically stable rhombohedral phase. The spontaneous formation of the seed layer enables us to grow orthorhombic Bi2Se3 on a variety of substrates including single-crystal silicon with different orientations, polycrystalline fluorine-doped tin oxide, and polycrystalline gold. The ability to stabilize the metastable phase through room-temperature electrodeposition in aqueous solution without requiring a single-crystal substrate broadens the range of applications for this semiconductor in optoelectronic and electrochemical devices.

CGR-Block: Correlated Feature Extractor and Geometric Feature Fusion for Point Cloud Analysis.

Point cloud processing based on deep learning is developing rapidly. However, previous networks failed to simultaneously extract inter-feature interaction and geometric information. In this paper, we propose a novel point cloud analysis module, CGR-block, which mainly uses two units to learn point cloud features: correlated feature extractor and geometric feature fusion. CGR-block provides an efficient method for extracting geometric pattern tokens and deep information interaction of point features on disordered 3D point clouds. In addition, we also introduce a residual mapping branch inside each CGR-block module for the further improvement of the network performance. We construct our classification and segmentation network with CGR-block as the basic module to extract features hierarchically from the original point cloud. The overall accuracy of our network on the ModelNet40 and ScanObjectNN benchmarks achieves 94.1% and 83.5%, respectively, and the instance mIoU on the ShapeNet-Part benchmark also achieves 85.5%, proving the superiority of our method.

Peptide-Based Capture of Chikungunya Virus E2 Protein Using Porous Silicon Biosensor.

The detection of pathogens presents specific challenges in ensuring that biosensors remain operable despite exposure to elevated temperatures or other extreme conditions. The most vulnerable component of a biosensor is typically the bioreceptor. Accordingly, the robustness of peptides as bioreceptors offers improved stability and reliability toward harsh environments compared to monoclonal antibodies that may lose their ability to bind target molecules after such exposures. Here, we demonstrate peptide-based capture of the Chikungunya virus E2 protein in a porous silicon microcavity biosensor at room temperature and after exposure of the peptide-functionalized biosensor to high temperature. Contact angle measurements, attenuated total reflectance-Fourier transform infrared spectra, and optical reflectance measurements confirm peptide functionalization and selective E2 protein capture. This work opens the door for other pathogenic biomarker detection using peptide-based capture agents on porous silicon and other surface-based sensor platforms.

A novel therapy for granulomatous lobular mastitis: Local heat therapy.

Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition that is characterized by granulomatous inflammation. GLM remains a refractory disease due to its failure to respond to routine anti-inflammatory therapies and its high recurrence rate. Thus, the present study aimed to investigate the application of local heat therapy in GLM as a potential therapeutic strategy. The results revealed that the application of local heat therapy was associated with a shortened remission time for GLM, while the remission and recurrence rates were similar to those of existing therapies. The median first remission time following local heat therapy was significantly decreased compared with that following corticosteroid therapy (5.30 months vs. 11.27 months; P<0.05). The remission rates were not significantly different between the local heat therapy (76.9%), extensive excision (90.4%) and the corticosteroid therapy (85.7%) groups (P>0.05). In addition, the recurrence rates were not statistically different between the groups (local heat therapy, 8.3%; extensive excision, 10%; and corticosteroid therapy, 10%; P>0.05). The local heat therapy showed mild adverse effects and shortened healing times compared to the other therapies; however, further confirmation is required.

Direct Observation and Control of Surface Termination in Perovskite Oxide Heterostructures.

Interfacial behavior of quantum materials leads to emergent phenomena such as quantum phase transitions and metastable functional phases. Probes for in situ and real time surface-sensitive characterization are critical for control during epitaxial synthesis of heterostructures. Termination switching in complex oxides has been studied using a variety of probes, often ex situ; however, direct in situ observation of this phenomena during growth is rare. To address this, we establish in situ and real time Auger electron spectroscopy for pulsed laser deposition with reflection high energy electron diffraction, providing structural and compositional surface information during film deposition. Using this capability, we show the direct observation and control of surface termination in heterostructures of SrTiO3 and SrRuO3. Density-functional-theory calculations capture the energetics and stability of the observed structures, elucidating their electronic behavior. This work demonstrates an exciting approach to monitor and control the composition of materials at the atomic scale for control over emergent phenomena and potential applications.

Impact of intraoperative radiotherapy on the perioperative period of patients after breast-conserving surgery.

BACKGROUND: To investigate the effect of intraoperative radiotherapy (IORT) in the perioperative period of patients after breast-conserving surgery (BCS). METHODS: The clinical data of 100 patients with early breast cancer undergoing breast-conserving surgery (BCS) followed by treatment with IORT using the Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany) (BCS + IORT group, n=100) between June 2016 and December 2019 were analyzed and compared with the data of 60 matched patients who only underwent breast-conserving therapy over the same period (BCS group, n=60). The surgical settings and postoperative acute complications between the groups were assessed. RESULTS: There was no significant statistical difference between the groups in terms of age, tumor size, grading, lymph node status, hormone receptor status, and human epidermal growth factor receptor 2 (HER-2) status (P>0.05). The BCS + IORT group had a significantly longer surgery duration (P<0.05), but there was no significant statistical difference in terms of intraoperative blood loss, amount of bleeding, drainage tube removal time, postoperative length of hospitalization, incision suture removal time, or incidence of postoperative complications (P>0.05). CONCLUSIONS: IORT using the Intrabeam system safely delivers radiation therapy, is well-tolerated, has acceptable acute toxicity, and does not significant increase the risk of surgery or the incidence of perioperative complications.

Spatial defects nanoengineering for bipolar conductivity in MoS2.

Understanding the atomistic origin of defects in two-dimensional transition metal dichalcogenides, their impact on the electronic properties, and how to control them is critical for future electronics and optoelectronics. Here, we demonstrate the integration of thermochemical scanning probe lithography (tc-SPL) with a flow-through reactive gas cell to achieve nanoscale control of defects in monolayer MoS2. The tc-SPL produced defects can present either p- or n-type doping on demand, depending on the used gasses, allowing the realization of field effect transistors, and p-n junctions with precise sub-µm spatial control, and a rectification ratio of over 104. Doping and defects formation are elucidated by means of X-Ray photoelectron spectroscopy, scanning transmission electron microscopy, and density functional theory. We find that p-type doping in HCl/H2O atmosphere is related to the rearrangement of sulfur atoms, and the formation of protruding covalent S-S bonds on the surface. Alternatively, local heating MoS2 in N2 produces n-character.

Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3.

BACKGROUND: Src associated with mitosis of 68 kDa (Sam68), is often highly expressed in human cancers. Overexpression of Sam68 has been shown to be correlated with poor survival prognosis in some cancer patients. However, little is known whether Sam68 plays a role in promoting metastasis in breast cancer. MATERIALS AND METHODS: The expression of Sam68 protein in breast cancer tissue was detected by immunohistochemistry. Trans-well assay, wound-healing, real-time PCR and Western blotting analysis were used to detect the effect of Sam68 on promoting EMT or metastasis of breast cancer. Next-generation RNA sequencing was used to analyze genes that may be regulated by Sam68. RESULTS: Sam68 plays a positive role in promoting breast cancer metastasis. Sam68 was found to be overexpressed in breast cancer along with lymph node metastasis. MMP-9 was also found to be overexpressed in breast cancer tissue and was correlated to the expression of Sam68 (P<0.01). Xenograft in NOD/SCID mice and in vitro experiments confirmed that the invasion and metastatic ability of breast cancer cells were regulated by Sam68. And EPHA3 could be up-regulated by Sam68 in breast cancer. CONCLUSION: High expression of Sam68 participates in breast cancer metastasis by up-regulating the EPHA3 gene.

Digital gene expression analysis in the gills of Ruditapes philippinarum after nitrite exposure.

Due to the overload of pollutants from highly intensive anthropic activities, nitrite accumulates in offshore seawater and has been a long-lasting pollutant to the healthy aquaculture of the mollusk. In the present study, Ruditapes philippinarum was used as the target bivalve to receive nitrite exposure at environmental concentration for 1 and 7 days. Differentially expressed genes (DEGs) were detected and analyzed by a digital gene expression (DGE) approach to describe the toxicity of nitrite on the bivalve at the gene level. In the N1 group, 185 DEGs were generated and enriched in six Gene Ontology (GO) terms, including oxidoreductase activity, heme binding, tetrapyrrole binding, iron ion binding, metal binding and cation binding. The DEGs in the N1 group were also enriched in two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, e.g., arachidonic acid metabolism and ovarian steroidogenesis. In the N7 group, 81 DEGs were generated without any GO enrichment but were enriched in five KEGG pathways, including protein processing in the endoplasmic reticulum, protein export, prion diseases, thyroid hormone synthesis and arachidonic acid metabolism. This suggested that nitrite exposure might cause adverse effects to the clams in several aspects, including oxidative damage, depressed immunity, and disorders in cell proliferation, hormone metabolism and tissue regeneration. Evaluation of oxidative stress indicated that nitrite exposure actually induced redox state imbalance by enhancing the contents of thiobarbituric acid reactive substances (TBARSs) and glutathione (GSH), and the activity of glutathione peroxidase (GSH-PX) but not superoxide dismutase (SOD). These results will provide valuable gene references for further study on the toxicology mechanism of bivalves under environmental nitrite stress.

A smartphone biosensor based on analysing structural colour of porous silicon.

We report a smartphone compatible, low-cost porous silicon biosensor, which correlates the structural colour of a porous silicon microcavity (PSiM) to spectral peak position. Molecules captured in the PSiM cause a colour change that can be quantified through image analysis. Minimal external accessories are employed. Spectrometer measurements of the PSiM reflectance spectrum shifts are carried out concurrently with the smartphone measurements to benchmark the accuracy of the smartphone biosensor. We estimate that the smartphone biosensor supports an equivalent accuracy of 0.33 nm for the detection of colour changes corresponding to spectral shifts of the PSiM. Biosensing functionality is demonstrated using a biotin-streptavidin assay with an estimated detection limit of 500 nM. The PSiM-smartphone biosensor is a promising platform for label-free point of care diagnostics.

Photonic crystal nanobeam biosensors based on porous silicon.

Photonic crystal (PhC) nanobeams (NB) patterned on porous silicon (PSi) waveguide substrates are demonstrated for the specific, label-free detection of oligonucleotides. These photonic structures combine the large active sensing area intrinsic to PSi sensors with the high-quality (Q) factor and low-mode volume characteristic of compact resonant silicon-on-insulator (SOI) PhC NB devices. The PSi PhC NB can achieve a Q-factor near 9,000 and has an approximately 40-fold increased active sensing area for molecular attachment, compared to traditional SOI PhC NB sensors. The PSi PhC NB exhibits a resonance shift that is more than one order of magnitude larger than that of a similarly designed SOI PhC NB for the detection of small chemical molecules and 16-base peptide nucleic acids. The design and fabrication of PSi PhC NB sensors are compatible with CMOS processing, sensor arrays, and integration with lab-on-chip systems.