Ag Nanoparticles@Au Nanograting Array as a 3D Flexible and Effective Surface-Enhanced Raman Scattering Substrate.

Surface-enhanced Raman scattering (SERS) is a powerful analytical technique for chemical identification, but it remains a great challenge to realize the large-scale and well-controlled fabrication of sensitive and repeatable SERS substrates. Here, we report a facile strategy to fabricate centimeter-sized periodic Au nanograting (Au-NG) decorated with well-arranged Ag nanoparticles (Ag-NPs) (denoted as Ag-NPs@Au-NG) as a three-dimensional (3D) flexible hybrid SERS substrate with high sensitivity and good reproducibility. The Au-NG patterns with periodic ridges and grooves are fabricated through nanoimprint lithography by employing a low-cost digital versatile disc (DVD) as a master mold, and the Ag-NPs are assembled by a well-controlled interface self-assembly method without any coupling agents. Multiple coupling electromagnetic field effects are created at the nanogaps between the Ag-NPs and Au-NG patterns, leading to high-density and uniform hot spots throughout the substrate. As a result, the Ag-NPs@Au-NG arrays demonstrate an ultrahigh SERS sensitivity as low as 10-13 M for rhodamine 6G with a high average enhancement factor (EF) of 1.85 × 108 and good signal reproducibility. For practical applications, toxic organic pollutants including crystal violet, thiram, and melamine have been successfully detected with high sensitivity at a low detection limit, showing a good perspective in the rapid detection of toxic organic pollutants.

Distribution of the Asiatic golden cat (Catopuma temminckii) and variations in its coat morphology in China.

Of the 12 wild felid species found in China, Asiatic golden cat (Catopuma temminckii) is one of the least studied species. This medium-sized cat with a prominently polymorphic coat was once distributed across much of southern China, but is believed to have experienced severe decline and range contraction during the past decades, primarily due to anthropogenic pressures. A lack of knowledge of its current distribution, ecology, and natural history has greatly hindered the implementation of conservation and management actions for this species. In this study, for the first time, we compiled the state-wide occurrence records (N = 409), mainly from the camera-trapping surveys, of Asiatic golden cats from 2008 to 2019, and predicted its distribution across the country through species distribution modeling using random forest algorithm. The results showed that the predicted habitats were mainly located in southwest China and suggested a rather low probability of possible current distribution across its vast historic range in central, eastern, and southern China. We divided its current range into four geographic regions (i.e., Qinling Mountains, Hengduan Mountains, East Himalayas, and southern Yunnan region) and considered the cats in each region as a regional population within the country. From the 287 camera-trapping detections with photographs and/or videos collected across all populations, we identified six coat morphs and determined their occurrence percentages: common golden (47.4%), spotted (20.9%), red (13.6%), dark cinnamon (10.1%), melanistic (7.0%), and gray (1.0%). The complexity of coat morph composition within regional populations showed an increasing gradient from northeast to southwest. Among the four regional populations, the East Himalayas hosted the highest abundance and coat variation with all six morphs recorded. Our study results update the current distribution and coat morphology variations of this elusive cat in China and provide important knowledge to guide future research and conservation planning for this threatened species.

Prostate cancer cell-derived exosomal IL-8 fosters immune evasion by disturbing glucolipid metabolism of CD8+ T cell.

Depletion of CD8+ T cells is a major obstacle in immunotherapy; however, the relevant mechanisms remain largely unknown. Here, we showed that prostate cancer (PCa) cell-derived exosomes hamper CD8+ T cell function by transporting interleukin-8 (IL-8). Compared to the low IL-8 levels detected in immune cells, PCa cells secreted the abundance of IL-8 and further accumulated in exosomes. The delivery of PCa cell-derived exosomes into CD8+ T cells exhausted the cells through enhanced starvation. Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Consequently, inhibition of PPARα and UCP1 restores CD8+ T cell proliferation by counteracting the effect of exosomal IL-8. This study revealed that the tumor exosome-activated IL-8-PPARα-UCP1 axis harms tumor-infiltrating CD8+ T cells by interfering with energy metabolism.

Two new sesquiterpenoids with glycosides from the leaves and stems of Schisandra chinensis (Turcz.) Baill.

Two previously undescribed glycosidic bisnorsesquiterpenoids A - B (1 - 2), together with two known compounds (3 - 4), were isolated from the leaves and stems of Schisandra chinensis. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, and HRESIMS). The anti-inflammatory activity, ABTS+ radical scavenging activity, and DPPH radical scavenging activity of compounds 1 - 4 were tested. However, all of these compounds showed only weak anti-inflammatory or antioxidant effects.

Solid-State Au Nanocone Arrays Substrate for Reliable SERS Profiling of Serum for Disease Diagnosis.

Surface-enhanced Raman scattering (SERS) is a widely used rapid and noninvasive method for detecting biological substances in serum samples and is commonly employed in disease screening and diagnosis. Solid-state nanoarray SERS substrates used in serum detection may cause spectral instability due to imperfections in the detection method. For the purpose of identifying optimal detection conditions, various dilution levels of the serum were tested in this study. The study found that a complete and stable serum SERS spectrum can be obtained when the serum is diluted by a factor of 50. The study reports the successful preparation of an Au nanocone array (Au NCA) plasmonic substrate with a uniform, controllable microstructure and high activity, achieved through a combination of PS colloidal sphere template-assisted reactive ion etching (RIE) process and magnetron sputtering deposition technology. Based on this substrate, a standard detection scheme was developed to obtain highly stable and repeatable serum SERS spectra. The study verified the reliability of the optimized serum detection scheme by comparing the SERS spectra of serum samples from healthy individuals and gastric cancer patients, and confirmed the potential benefits of the scheme for disease screening and diagnosis.

Self-Assembled Bifunctional Copper Hydroxide/Gold-Ordered Nanoarray Composites for Fast, Sensitive, and Recyclable SERS Detection of Hazardous Benzene Vapors.

Volatile organic compounds (VOCs), particularly monoaromatic hydrocarbon compounds (MACHs), pose a potential risk to the atmospheric environment and human health. Therefore, the progressive development of efficient detection methodologies is a pertinent need, which is still a challenge at present. In this study, we present a rapid and sensitive method to detect trace amounts of MACHs using a bifunctional SERS composite substrate. We prepared an Au/SiO2 enhanced layer and a porous Cu(OH)2 adsorption layer via microfluidic-assisted gas-liquid interface self-assembly. The composite substrate effectively monitored changes in benzaldehyde using time-varying SERS spectra, and track-specifically identified various VOCs such as benzene, xylene, styrene, and nitrobenzene. In general, the substrate exhibited a rapid response time of 20 s to gaseous benzaldehyde, with a minimum detection concentration of less than 500 ppt. Further experimental assessments revealed an optimum Cu(OH)2 thickness of the surrounding adsorption layer of 150 nm, which can achieve an efficient SERS response to MACHs. Furthermore, the recoverable and reusable property of the composite substrate highlights its practicality. This study presents a straightforward and efficient approach for detecting trace gaseous VOCs using SERS, with significant implications in the designing of SERS substrates for detecting other VOCs.

Stromal cell-derived small extracellular vesicles enhance radioresistance of prostate cancer cells via interleukin-8-induced autophagy.

Radiation is a curative treatment for localized prostate cancer (PCa). Unfortunately, radiotherapeutic efficacy is often diminished when patients develop more aggressive or metastatic phenotypes. Recent studies have demonstrated that extracellular vesicles participate in cancer therapeutic resistance by delivering small bioactive molecules, such as small non-coding RNAs. Here, we show that stromal cell-derived small extracellular vesicles (sEVs) facilitate the radioresistance of PCa cells by transporting interleukin-8 (IL-8). Indeed, prostatic stromal cells secrete more IL-8 than AR-positive PCa cells, which can be accumulated in sEVs. Intriguingly, the uptake of stromal cells-derived sEVs by radiosensitive PCa cells enhanced their radioresistance, which could be attenuated by silencing CXCL8 in stromal cells or inhibiting its receptor CXCR2 in PCa cells. sEV-mediated radioresistance has been validated in zebrafish and mouse xenograft tumours. Mechanistically, the uptake of stromal sEVs triggers the AMPK-activated autophagy pathway in PCa cells under the irradiation condition. Consequently, inactivating AMPK efficiently resensitized radiotherapy either by utilizing an AMPK inhibitor or silencing AMPKα in PCa cells. Furthermore, chloroquine (CQ), a lysosomal inhibitor, sufficiently resensitized radiotherapy via blockade of autophagolysosome fusion, leading to autophagosome accumulation in PC cells. Collectively, these results suggest that stromal cells enhance the radioresistance of PCa cells mainly through sEVs that deliver IL-8.

An integrated network pharmacology approach reveals that Darutigenol reduces inflammation and cartilage degradation in a mouse collagen-induced arthritis model by inhibiting the JAK-STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown. AIMS OF THE STUDY: The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment. RESULTS: DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints. CONCLUSIONS: To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model.

Defect Damping-Enhanced Plasmonic Photothermal Conversion.

Significantly increasing the photothermal conversion of plasmonic nanostructured particles (PNPs) is a common goal for all applications of thermoplasmonics, but it is still in challenge, especially for PNPs with the morphology and composition required for a specific photothermal application. Here, we present a concept of defect-induced damping-enhanced photothermal conversion, which favors PNP intrinsic properties. A model of a defect-damped harmonic oscillator is established to depict photothermal conversion correlation with the structure of PNPs and is capable of accurately reproducing the optical performance of the PNPs with the local surface plasmon resonance far from the interband transition. The theoretical model analyses demonstrate that the defect-induced damping can significantly suppress the light scattering of the PNPs and effectively improve their photothermal conversion efficiency. Especially for the PNPs with a sufficiently large size (larger than ∼100 nm for Au and Ag), we show that defect-induced damping can significantly enhance their light absorption and photothermal performances. These are experimentally confirmed. Typically, defect-enriched Au nanostars with ∼100-150 nm profile size were fabricated and showed much higher photothermal performance and a big increment by 23% in photothermal conversion efficiency, compared with the normal (or defect-impoverished) counterpart. Furthermore, the in vitro and in vivo biological experiments demonstrate that this defect-enriched PNP can indeed exhibit significantly higher photothermal performance than the normal counterpart in cells and mouse tumors, which confirms the validity of the presented strategy in typical practical applications. This work provides a strategy to intrinsically and significantly enhance plasmonic photothermal conversion of PNPs with a sufficiently large size, which is not only suitable for PNPs with the morphology and composition required for specific applications but also can be combined with existing strategies to further increase their photothermal performance.

Regional homogeneity of adolescents with high-functioning autism spectrum disorder and its association with symptom severity.

BACKGROUND AND PURPOSE: Previous studies have revealed abnormal regional homogeneity (ReHo) in individuals with autism spectrum disorder (ASD); however, there is little consistency across the findings within these studies, partly due to small sample size and great heterogeneity among participants between studies. Additionally, few studies have explored the association between ReHo aberrance and clinical symptoms in individuals with ASD. METHODS: Forty-eight adolescents with high-functioning ASD and 63 group-matched typically developing (TD) controls received functional magnetic resonance imaging at rest. Group-level analysis was performed to detect differences in ReHo between ASD and TD. Evaluation of symptom severity in individuals with ASD was based on the Autism Behavior Checklist (ABC). Voxel-wise correlation analysis was undergone to examine the correlations between the symptom severity and ReHo map in individuals with ASD within brain areas with ReHo abnormalities. RESULTS: Compared with the TD controls, individuals with ASD exhibited increased ReHo in the bilateral anterior cingulate cortex, left caudate, right posterior cerebellum (cerebellar tonsil), and bilateral brainstem and decreased ReHo in the left precentral gyrus, left inferior parietal lobule, bilateral postcentral gyrus, and right anterior cerebellum (culmen). The correlation analysis indicated that the ReHo value in the brainstem was negatively associated with the ABC total scores and the scores of Relating factor, respectively. CONCLUSIONS: Our findings indicated that widespread ReHo abnormalities occurred in ASD, shedding light on the underlying neurobiology of pathogenesis and symptomatology of ASD.

High-Density-Nanotips-Composed 3D Hierarchical Au/CuS Hybrids for Sensitive, Signal-Reproducible, and Substrate-Recyclable SERS Detection.

Surface-enhanced Raman scattering (SERS) provides an unprecedented opportunity for fingerprinting identification and trace-level detection in chemistry, biomedicine, materials, and so on. Although great efforts have been devoted to fabricating sensitive plasmonic nanomaterials, it is still challenging to batch-produce a SERS substrate with high sensitivity, good reproducibility, and perfect recyclability. Here, we describe a facile fabrication of three-dimensional (3D) hierarchical Au/CuS nanocomposites, in which high-density Au nanotips enable highly SERS-active sensing, and the well-defined microflower (MF) geometry produces perfect signal reproducibility (RSD < 5%) for large laser spot excitations (>50 µm2), which is particularly suitable for practical on-site detection with a handheld Raman spectrometer. In addition, a self-cleaning ability of this Au/CuS Schottky junction photocatalyst under sunlight irradiation allows complete removal of the adsorbed analytes, realizing perfect regeneration of the SERS substrates over many cycles. The mass-production, ultra-sensitive, high-reproducibility, and fast-recyclability features of hierarchical Au/CuS MFs greatly facilitate cost-effective and field SERS detection of trace analytes in practice.

Surface Roughening of Pt-Polystyrene Spherical Janus Micromotors for Enhanced Motion Speed.

Spherical Janus micromotors (SJMs) have attracted much attention, and their high-speed motion is highly desired due to their various potential applications. However, the conventional template-deposition method often leads to an active Pt coating with a smooth surface, which is unbeneficial to speed enhancement in terms of catalytic reaction. Here, a facile surface roughening method is presented to fabricate the Pt-polystyrene (PS) SJMs with rough Pt surface (or Ptr-PS SJMs) by plasma-etching the PS colloidal monolayer and then depositing Pt. The Ptr-PS SJMs can exhibit directional motion pushed by the Pt in the various H2O2 solutions, and they show much higher motion speeds than the Pt-PS SJMs with smooth Pt surfaces at the same H2O2 concentration. The Pt-pushed motion is related to the locally asymmetric catalytic reaction of the Pt coating on PS. The speed is also associated with the surface roughness of the Pt coating. The Pt film with a rough surface causes enhanced motion speed due to the improvement of reaction catalytic activity. This work presents a new route to enhancing the motor motion speed, which is of significance in designing micromotors with high-speed motion.

Abnormalities of Gray Matter Volume and Its Correlation with Clinical Symptoms in Adolescents with High-Functioning Autism Spectrum Disorder.

Background: Previous studies have indicated abnormal gray matter volume (GMV) in individuals with autism spectrum disorder (ASD); however, there is little consistency across the findings within these studies, partly due to small sample size and great heterogeneity among participants between studies. Additionally, few studies have explored the correlation between clinical symptoms and GMV abnormalities in individuals with ASD. Here, the current study examined GMV alterations in whole brain and their correlations with clinical symptoms in a relatively large and homogeneous sample of participants with ASD matched typically developing (TD) controls. Methods: Forty-eight adolescents with high-functioning ASD and 29 group-matched TD controls underwent structural magnetic resonance images. Voxel-based morphometry was applied to investigate regional GMV alterations. The participants with ASD were examined for the severity of clinical symptoms with Autism Behavior Checklist (ABC). The relationship between GMV abnormalities and clinical symptoms was explored in ASD group using voxel-wise correlation analysis within brain regions that showed significant GMV alterations in individuals with ASD compared with TD controls. Results: We found increased GMV in multiple brain regions, including the inferior frontal gyrus, medial frontal gyrus, superior frontal gyrus, superior temporal gyrus, occipital pole, anterior cingulate, cerebellum anterior lobe, cerebellum posterior lobe, and midbrain, as well as decreased GMV in cerebellum posterior lobe in individuals with ASD. The correlation analysis showed the GMV in the left fusiform was negatively associated with the scores of sensory factor, and the GMV in the right cerebellum anterior lobe was positively associated with the scores of social self-help factor. Conclusion: Our results indicated that widespread GMV abnormalities of brain regions occurred in individuals with ASD, suggesting a potential neural basis for the pathogenesis and symptomatology of ASD.

Abnormally Weak Surface-Enhanced Raman Scattering Activity of Tip-Rich Au Nanostars: The Role of Interfacial Defects.

Designing and regulating the geometry of a given plasmonic metal (Au, Ag, etc.) has become one of the most efficient approaches to achieve highly active surface-enhanced Raman spectroscopy (SERS) substrates, but this work demonstrates that plain efforts on this may not be enough. Here, we report that the often-neglected inner crystal defects also have huge impacts on the SERS activity, through a case of Au nanostars (NSs) with good SERS geometry but rich in defects. The results suggest that the interfacial defects (twin boundaries and superlattices) in the NSs aggravate the electronic oscillation damping via reducing the free path of electron scattering. This eventually results in weak local electromagnetic fields near the NS surfaces (or weak SERS activity of the NSs). This study has demonstrated the huge impact of interfacial defects on SERS activity and thus has a significant guideline for the design and fabrication of efficient SERS substrates.

RelB upregulates PD-L1 and exacerbates prostate cancer immune evasion.

BACKGROUND: The interaction between programmed death receptor (PD-1) and its ligand (PD-L1) is essential for suppressing activated T-lymphocytes. However, the precise mechanisms underlying PD-L1 overexpression in tumours have yet to be fully elucidated. Here, we describe that RelB participates in the immune evasion of prostate cancer (PCa) via cis/trans transcriptional upregulation of PD-L1. METHODS: Based on transcriptome results, RelB was manipulated in multiple human and murine PCa cell lines. Activated CD4+ and CD8+ T cells were cocultured with PCa cells with different levels of RelB to examine the effect of tumourous RelB on T cell immunity. Male mice were injected with murine PCa cells to validate the effect of RelB on the PD-1/PD-L1-mediated immune checkpoint using both tumour growth and metastatic experimental models. RESULTS: PD-L1 is uniquely expressed at a high level in PCa with high constitutive RelB and correlates with the patients' Gleason scores. Indeed, a high level of PD-L1 is associated with RelB nuclear translocation in AR-negative aggressive PCa cells. Conversely, the silencing of RelB in advanced PCa cells resulted in reduced PD-L1 expression and enhanced susceptibility of PCa cells to the T cell immune response in vitro and in vivo. Mechanistically, a proximal NF-κB enhancer element was identified in the core promoter region of the human CD274 gene, which is responsible for RelB-mediated PD-L1 transcriptional activation. This finding provides an informative insight into immune checkpoint blockade by administering RelB within the tumour microenvironment. CONCLUSION: This study deciphers the molecular mechanism by which tumourous RelB contributes to immune evasion by inhibiting T cell immunity via the amplification of the PD-L1/PD-1-mediated immune checkpoint.

Social skill training for children with autistic spectrum disorder on the uncertainty of the disease from mothers / 中国学校卫生

Objective@#To improve the social skills of children with ASD by using Program for the Education and Enrichment of Relational Skills(PEERS ), and to reduce the uncertainty towards ASD and negative emotions for mothers of ASD children.@*Methods@#From September to October 2017, 30 dyads of autistic mother and child were recruited and divided into intervention group and control group (15 mother child dyads each). Based on the content of PEERS social skill, cognitive behavior therapy was delivered in group format, through demonstration, role play and group exercise. At the same time, mother child dyads were trained using parallel social technology. Mothers and children with ASD were investigated using Parents Perception of Uncertainty Scale (PPUS), Patient Health Questionnaire 9 (PHQ-9), Chinese Version of the Beck Depression Inventory II(BDI-Ⅱ-C), Beck Anxiety Inventory (BAI), State Trait Anxiety Inventory(STAI-Form Y), and Autism Behavior Checklist (ABC), Cildhood Autism Rating Scale (CARS), and Social Communication Questionnaire (SCQ).@*Results@#Changes in ASD symptom score in children and emotional score of mothers in the intervention group were less than 0. The total score of mother disease uncertainty(74.93±13.58, 90.40± 9.21 ), ambiguity(31.13±7.07, 38.93±4.73), lack of clarity information(11.93±2.09, 13.80±2.54), unpredictability(9.60±1.99, 12.07±2.89), significantly changed after intervention( t =-3.65, -3.55, -2.20, -2.72, P <0.05).@*Conclusion@#Social PEERS group intervention can enhance the social skills of children with ASD, reduce uncertainty of illness among mother of ASD children. Timely disease related information, guidance for mothers to actively participate in child care and training, might help to reduce cognitive bias, depressive and anxiety symptoms among mothers.

Optimal Excitation Wavelength for Surface-Enhanced Raman Spectroscopy: The Role of Chemical Interface Damping.

The optimal excitation wavelength (OEW) for surface-enhanced Raman spectroscopy (SERS) is generally close to that of the local surface plasmon resonance (LSPR). In some cases, however, the OEW is significantly longer than that of the observed LSPR. Its origin is still unclear and controversial. Here, we propose a chemical interface damping (CID)-based mechanism and reveal the origin of the OEW's deviation from the LSPR by simulation and experiments using gold nanorods as the model material. Simulations show that the molecular adsorption induces CID, which causes a red-shift of the near-field peak relative to the far-field one, and that the chemical adsorption of target molecules on the plasmonic metals with enough strong CID would induce a significant red-shift of the OEW, even to the region far beyond the LSPR. Finally, we experimentally confirm the validity of the proposed CID theory and demonstrate the significant influence of the CID on the OEW during SERS measurements.

Quantitative Surface-Enhanced Raman Spectroscopy for Field Detections Based on Structurally Homogeneous Silver-Coated Silicon Nanocone Arrays.

Practical application of surface-enhanced Raman spectroscopy (SERS) is greatly limited by the inaccurate quantitative analyses due to the measuring parameter's fluctuations induced by different operators, different Raman spectrometers, and different test sites and moments, especially during the field tests. Herein, we develop a strategy of quantitative SERS for field detection via designing structurally homogeneous and ordered Ag-coated Si nanocone arrays. Such an array is fabricated as SERS chips by depositing Ag on the template etching-induced Si nanocone array. Taking 4-aminothiophenol as the typical analyte, the influences of fluctuations in measuring parameters (such as defocusing depth and laser powers) on Raman signals are systematically studied, which significantly change SERS measurements. It has been shown that the silicon underneath the Ag coating in the chip can respond to the measuring parameters' fluctuations synchronously with and similar to the analyte adsorbed on the chip surface, and the normalization with Si Raman signals can well eliminate the big fluctuations (up to 1 or 2 orders of magnitude) in measurements, achieving highly reproducible measurements (mostly, <5% in signal fluctuations) and accurate quantitative SERS analyses. Finally, the simulated field tests demonstrate that the developed strategy enables quantitatively analyzing the highly scattered SERS measurements well with 1 order of magnitude in signal fluctuation, exhibiting good practicability. This study provides a new practical chip and reliable quantitative SERS for the field detection of real samples.

Small extracellular vesicles deliver TGF-ß1 and promote adriamycin resistance in breast cancer cells.

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV-mediated TGF-ß1 intercellular transfer is involved in the drug-resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis-associated cytokines present at the high levels in sEVs from the resistant cells compared with their levels in sEVs from the sensitive cells, particularly TGF-ß1 is enriched in sEVs from the resistant cells. The sEV-mediated TGF-ß1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEV-mediated drug-resistant transmission by delivering TGF-ß1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEV-mediated TGF-ß1 intercellular transfer contributes to adriamycin resistance in BCa.

Small extracellular vesicle-mediated Hsp70 intercellular delivery enhances breast cancer adriamycin resistance.

Adriamycin (ADR) resistance poses a significant challenge for successfully treating breast cancer (BCa). The mechanism underlying intrinsically acquisition of the resistance remains to be fully elucidated. Here, we describe that small extracellular vesicles (sEVs) mediated Hsp70 transfer is implicated in ADR resistance. The resistant cells derived sEVs were incubated with sensitive cells, thereby transmitting the resistant phenotype to the recipient cells. The internalization of the sEVs in the recipient cells and sEV-mediated Hsp70 transfer into mitochondria were examined by confocal microscope and transmission electron microscopy (TEM). Oxygen consumption rate (OCR) incorporated with extracellular acidification rate (ECAR) was quantified by Seahorse XF Analyzer. Mechanistically, sEVs transported Hsp70, leading to increased reactive oxygen species (ROS) and impaired mitochondria in the recipient cells, thereby inhibiting respiration but promoting glycolysis. The sEVs effect on the metabolism of the recipient cells was alleviated by silencing Hsp70 in sEVs donor cells. The aspect of sEV-Hsp70 on drug-resistant transmission was further validated by tumor zebrafish xenografts. The finding from this work suggests that sEV-mediated Hsp70 intercellular delivery enhances ADR resistance mainly through reprogramming the recipient cell energy metabolism.