Inhibition of Notch1 reverses EMT and chemoresistance to cisplatin via direct downregulation of MCAM in triple-negative breast cancer cells.

Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin-resistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.

FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. METHODS: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. RESULTS: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. CONCLUSION: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

Advanced One- and Two-Dimensional Mesh Designs for Injectable Electronics.

The unique structure and mechanical properties of syringe-injectable mesh electronics have enabled seamless tissue integration and stable chronic recording of the activities of the same neurons on a year scale. Here, we report studies of a series of structural and mechanical mesh electronics design variations that allow injection using needles at least 4-fold smaller than those previously reported to minimize the footprint during injection of the electronics in soft matter and tissue. Characterization of new ultraflexible two-dimensional (2D) and one-dimensional (1D) probes has demonstrated reproducible injection of the newly developed mesh electronics designs via needles as small as 100 µm in inner diameter (ID) with reduced injection volumes. In vitro hydrogel and in vivo mouse brain studies have shown that ultraflexible 2D and 1D probes maintain their structural integrity and conformation post-injection after being transferred through the reduced diameter needles. In addition, analysis of the variation of the post-injection mesh cross sections suggests a smaller degree of tissue deformation and relaxation with decreasing needle diameters. The capability to implement rational design for mesh electronic probes that can be delivered via much smaller diameter needles should open up new opportunities for integration of electronics with tissue and soft matter in fundamental and translational studies.

Mid-Infrared Chalcogenide Waveguides for Real-Time and Nondestructive Volatile Organic Compound Detection.

A mid-infrared (mid-IR) sensor chip was demonstrated for volatile organic compound (VOC) detection. The sensor consisted of As2Se3 optical waveguides built by microelectronic fabrication processes. The VOC sensing performance was characterized by measuring acetone and ethanol vapors at their characteristic C-H absorption from λ = 3.40 to 3.50 µm. Continuous VOC detection with <5 s response time was achieved by measuring the intensity attenuation of the waveguide mode. The miniaturized noninvasive VOC sensor can be applied to breath analysis and environmental toxin monitoring.

Mid-infrared spectrometer using opto-nanofluidic slot-waveguide for label-free on-chip chemical sensing.

A mid-infrared (mid-IR) spectrometer for label-free on-chip chemical sensing was developed using an engineered nanofluidic channel consisting of a Si-liquid-Si slot-structure. Utilizing the large refractive index contrast (Δn ∼ 2) between the liquid core of the waveguide and the Si cladding, a broadband mid-IR lightwave can be efficiently guided and confined within a nanofluidic capillary (≤100 nm wide). The optical-field enhancement, together with the direct interaction between the probe light and the analyte, increased the sensitivity for chemical detection by 50 times when compared to evanescent-wave sensing. This spectrometer distinguished several common organic liquids (e.g., n-bromohexane, toluene, isopropanol) accurately and could determine the ratio of chemical species (e.g., acetonitrile and ethanol) at low concentration (<5 µL/mL) in a mixture through spectral scanning over their characteristic absorption peaks in the mid-IR regime. The combination of CMOS-compatible planar mid-IR microphotonics, and a high-throughput nanofluidic sensor system, provides a unique platform for chemical detection.

Eriogynapyretorum (Lepidoptera, Saturniidae) parasitoid species investigated in Fujian, China.

Eriogynapyretorum Westwood is a notorious defoliator of Camphoraofficinarum Nees that causes large economic and ecological losses in planted forests. To understand the importance of suppressing the population of E.pyretorum on natural parasitoids, a four-years investigation was conducted in the field. Four egg parasitoid species Ooencyrtuskuvanae Howard, Trichogrammachionis Ishii, Telenomus sp. and Anastatusdexingensis Sheng & Wang were captured in the wild. One of these is the dominant endoparasitoid species T.chionis, which has a quicker developmental time (8.33 d), more offspring (8.39/egg) and a greater parasitism rate (89.54%). With different elevation distributions, the parasitism rates for Kriechbaumerellalongiscutellaris Qian & He, Gregopimplahimalayensis (Cameron), Theroniadepressa (Gupta) and Xanthopimplakonowi (Krieger) were 17.29%, 2.10%, 4.23% and 0.83%, respectively. Female longevity (47.75 d), offspring (13.36/pupa) and sex ratio (1.16:1) were compared in four pupal parasitoids and K.longiscutellaris was the most abundant species of E.pyretorum in Fujian Province.

A survey on pupae parasitoid species of Dendrolimushoui (Lajonquiere) (Lepidoptera, Lasiocampidae) in China.

Cryptomeriajaponicavar.sinensis Miquel in south China is currently overwhelmingly infested by a native caterpillar species, Dendrolimushoui (Lepidoptera), which is causing severe economic losses and ecological disasters in both planted and natural forests. Our results include report of five parasitoid species and eight parasitoid flies within D.houi and a dominant endoparasitoid species Kriechbaumerelladendrolimi, which attacks pupae of D.houi with a high parasitism rate. This result might be helpful to improve better identification and application in the future for potential biological control of D.houi in the forests of east Asia.

Online short videos promoting public breast cancer literacy: a pretest-posttest control group trial on efficiency, attitude, and influencing factors.

Background: Short videos on social media are playing an increasingly important role in cancer health education today. It is important to explore how the actual communication effect of health videos and the knowledge absorption of users are influenced by different factors of the video creation process. Objective: The objective of our study is to access the factors influencing breast cancer health education through short videos on efficiency and quality. Methods: Three pairs of videos about breast health were created and participants completed questionnaires before and after watching the videos. A paired t-test was used to analyze within-group change scores. RM-ANOVA was used to assess the relationship between the pretest, posttest, and three variables. Results: Watching short videos can significantly increase viewers' knowledge of related health topics (p < 0.05). The viewers' concentration level while watching was significantly higher for the video with background music (BGM) than for the video without BGM (p = 0.006). The viewers' willingness to share was significantly higher for the video with a progress bar than for the video without a progress bar (p = 0.02). Using an interpreter wearing a doctor's uniform instead of casual wear and setting a progress bar can significantly improve the efficiency of knowledge absorption (p < 0.05). Conclusion: A uniformed interpreter, BGM and a progress bar are factors influencing the efficiency of short health videos. They can be applied in video making to explore better ways of promoting cancer health education in the new mobile Internet environment.

Management of acute portomesenteric venous thrombosis induced by protein S deficiency: report of a case.

Hereditary protein S deficiency is a risk factor which may predispose patients to venous thrombosis. Deep venous thrombosis of the lower extremities can result in painful congestion, while the presence of mesenteric venous thrombosis (MVT) can cause abdominal emergencies. We herein report a protein S-deficient patient presenting with acute portomesenteric venous thrombosis. Early management using anticoagulant therapy was initially successful. However, the subsequent bowel stricture resulting from the ischemic insult was further managed with a surgical bypass. The patient was kept on long-term thrombophylaxis. The treatment strategy for MVT with bowel ischemia has evolved from aggressive portomesenteric thrombectomy with resection of the involved bowel, to conservative anticoagulation to recanalize thrombotic mesenteric veins with bowel preservation. Surgical intervention is reserved for transmural necrosis or bowel perforation. The perioperative thrombophylaxis of inherited thrombophilic patients is also important for preventing further thromboembolic events.

Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy.

Background: Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population. Methods: A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients' outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients' survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker. Results: Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066]). Conclusions: Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.

Choledochal cyst originating from primary sclerosing cholangitis in a child.

Choledochal cysts are common in Asian children. Primary sclerosing cholangitis (PSC), which is characterized by inflammation and fibrosis and may lead to bile duct stricture over the intrahepatic or extrahepatic bile duct, is rare in children. Here we report a case of a 10-year-old boy who presented with a choledochal cyst originating from PSC. He had suffered from repeated abdominal pain and cholangitis for 3 years. A type IV choledochal cyst was suspected from the ultrasound and computed tomography image showing a distended gallbladder and dilatation of the bilateral intrahepatic duct at the hepatic hilar area and common bile duct (CBD). During laparotomy, a markedly distended gallbladder was noted and was shown to have no communication with the CBD by intraoperative cholangiogram. Choledochal cysts with extrahepatic and intrahepatic duct dilatation at the hilar area and marked stenosis with nearly total obstruction of the distal CBD were noted. Hepaticojejunostomy was performed. The histopathologic findings demonstrated a typical PSC picture. The patient's postoperative course was uneventful for 8 months after surgery, and he received no medication during a regular follow-up.

CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer.

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer.

Biotransformations and cytotoxicity of eleven graphene and inorganic two-dimensional nanomaterials using simulated digestions coupled with a triculture in vitro model of the human gastrointestinal epithelium.

Background: Engineered nanomaterials (ENMs) have already made their way into myriad applications and products across multiple industries. However, the potential health risks of exposure to ENMs remain poorly understood. This is particularly true for the emerging class of ENMs know as 2-dimensional nanomaterials (2DNMs), with a thickness of one or a few layers of atoms arranged in a planar structure. Methods: The present study assesses the biotransformations and in vitro cytotoxicity in the gastrointestinal tract of 11 2DNMs, namely graphene, graphene oxide (GO), partially reduced graphene oxide (prGO), reduced graphene oxide (rGO), hexagonal boron nitride (h-BN), molybdenum disulphide (MoS2), and tungsten disulphide (WS2). The evaluated pristine materials were either readily dispersed in water or dispersed with the use of a surfactant (Na-cholate or PF108). Materials dispersed in a fasting food model (FFM, water) were subjected to simulated 3-phase (oral, gastric, and small intestinal) digestion to replicate the biotransformations that would occur in the GIT after ingestion. A triculture model of small intestinal epithelium was used to assess the effects of the digested products (digestas) on epithelial layer integrity, cytotoxicity, viability, oxidative stress, and initiation of apoptosis. Results: Physicochemical characterization of the 2DNMs in FFM dispersions and in small intestinal digestas revealed significant agglomeration by all materials during digestion, most prominently by graphene, which was likely caused by interactions with digestive proteins. Also, MoS2 had dissolved by ~75% by the end of simulated digestion. Other than a low but statistically significant increase in cytotoxicity observed with all inorganic materials and graphene dispersed in PF108, no adverse effects were observed in the exposed tricultures. Conclusions: Our results suggest that occasional ingestion of small quantities of 2DNMs may not be highly cytotoxic in a physiologically relevant in vitro model of the intestinal epithelium. Still, their inflammatory or genotoxic potential after short- or long-term ingestion remains unclear and needs to be studied in future in vitro and in vivo studies. These would include studies of effects on co-ingested nutrient digestion and absorption, which have been documented for numerous ingested ENMs, as well as effects on the gut microbiome, which can have important health implications.

Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN.

Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

A negative binomial regression model for risk estimation of 0-2 axillary lymph node metastases in breast cancer patients.

Extensive clinical trials indicate that patients with negative sentinel lymph node biopsy do not need axillary lymph node dissection (ALND). However, the ACOSOG Z0011 trial indicates that patients with clinically negative axillary lymph nodes (ALNs) and 1-2 positive sentinel lymph nodes having breast conserving surgery with whole breast radiotherapy do not benefit from ALND. The aim of this study is therefore to identify those patients with 0-2 positive nodes who might avoid ALND. A total of 486 patients were eligible for the study with 212 patients in the modeling group and 274 patients in the validation group, respectively. Clinical lymph node status, histologic grade, estrogen receptor status, and human epidermal growth factor receptor 2 status were found to be significantly associated with ALN metastasis. A negative binomial regression (NBR) model was developed to predict the probability of having 0-2 ALN metastases with the area under the curve of 0.881 (95% confidence interval 0.829-0.921, P < 0.001) in the modeling group and 0.758 (95% confidence interval 0.702-0.807, P < 0.001) in the validation group. Decision curve analysis demonstrated that the model was clinically useful. The NBR model demonstrated adequate discriminative ability and clinical utility for predicting 0-2 ALN metastases.

Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case-control validation.

OBJECTIVE: To extensively use blood transcriptome analysis to identify potential diagnostic and therapeutic targets for cardiovascular diseases. METHODS: Two gene expression datasets (GSE59867 and GSE62646) were downloaded from GEO DataSets to identify altered blood transcriptomes in patients with ST-segment elevation myocardial infarction (STEMI) compared to stable coronary artery disease (CAD). Thereafter, several computational approaches were taken to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Finally, the expression of dysregulated two hub genes-suppressor of cytokine signaling 3 (SOCS3) and haptoglobin (HP)-were validated in a case-control study. RESULTS: A total of 119 DEGs were identified in the discovery phase, consisting of 71 downregulated genes and 48 upregulated genes; two hub modules consisting of two hub genes-SOCS3 and HP-were identified. In the validation phase, both SOCS3 and HP were significantly downregulated in the stable CAD and acute coronary syndrome (ACS) patients when compared with healthy controls. Meanwhile, HP was significantly upregulated in STEMI patients when compared with stable CAD patients (p=0.041). Logistic regression analysis indicated that: downregulated expression of HP correlated with increased risk of CAD [odds ratio (OR)=0.52, 95% confidence interval (CI)=0.31~0.87, p=0.013]; and downregulated expression of SOCS3 correlated with increased risk of ACS (OR=0.66, 95% CI=0.46~0.94, p=0.023) when age, gender, history of hyperlipidemia, diabetes and hypertension were included as covariates. CONCLUSION: Future clarification of how SOCS3 and HP influence the pathogenesis of disease may pave the way for the development of novel diagnostic and therapeutic methods.

Room-Temperature Phosphorescence and Low-Energy Induced Direct Triplet Excitation of Alq3 Engineered Crystals.

Crystal engineering is a practical approach for tailoring material properties. This approach has been widely studied for modulating optical and electrical properties of semiconductors. However, the properties of organic molecular crystals are difficult to control following a similar engineering route. In this Letter, we demonstrate that engineered crystals of Alq3 and Ir(ppy)3 complexes, which are commonly used in organic light-emitting technologies, possess intriguing functional properties. Specifically, these structures not only process efficient low-energy induced triplet excitation directly from the ground state of Alq3 but also can show strong emission at the Alq3 triplet energy level at room temperatures. We associate these phenomena with local deformations of the host matrix around the guest molecules, which in turn lead to a stronger host-guest triplet-triplet coupling and spin-orbital mixing.

Integrative Omics Analysis Reveals Soluble Cadherin-3 as a Survival Predictor and an Early Monitoring Marker of EGFR Tyrosine Kinase Inhibitor Therapy in Lung Cancer.

PURPOSE: EGFR tyrosine kinase inhibitors (EGFR-TKI) benefit patients with advanced lung adenocarcinoma (ADC) harboring activating EGFR mutations. We aimed to identify biomarkers to monitor and predict the progression of patients receiving EGFR-TKIs via a comprehensive omic analysis. EXPERIMENTAL DESIGN: We applied quantitative proteomics to generate the TKI resistance-associated pleural effusion (PE) proteome from patients with ADC with or without EGFR-TKI resistance. Candidates were selected from integrated genomic and proteomic datasets. The PE (n = 33) and serum (n = 329) levels of potential biomarkers were validated with ELISAs. Western blotting was applied to detect protein expression in tissues, PEs, and a cell line. Gene knockdown, TKI treatment, and proliferation assays were used to determine EGFR-TKI sensitivity. Progression-free survival (PFS) and overall survival (OS) were assessed to evaluate the prognostic values of the potential biomarkers. RESULTS: Fifteen proteins were identified as potential biomarkers of EGFR-TKI resistance. Cadherin-3 (CDH3) was overexpressed in ADC tissues compared with normal tissues. CDH3 knockdown enhanced EGFR-TKI sensitivity in ADC cells. The PE level of soluble CDH3 (sCDH3) was increased in patients with resistance. The altered sCDH3 serum level reflected the efficacy of EGFR-TKI after 1 month of treatment (n = 43). Baseline sCDH3 was significantly associated with PFS and OS in patients with ADC after EGFR-TKI therapy (n = 76). Moreover, sCDH3 was positively associated with tumor stage in non-small cell lung cancer (n = 272). CONCLUSIONS: We provide useful marker candidates for drug resistance studies. sCDH3 is a survival predictor and real-time indicator of treatment efficacy in patients with ADC treated with EGFR-TKIs.

Flexible Mid-infrared Photonic Circuits for Real-time and Label-Free Hydroxyl Compound Detection.

Chip-scale chemical detections were demonstrated by mid-Infrared (mid-IR) integrated optics made by aluminum nitride (AlN) waveguides on flexible borosilicate templates. The AlN film was deposited using sputtering at room temperature, and it exhibited a broad infrared transmittance up to λ = 9 µm. The AlN waveguide profile was created by microelectronic fabrication processes. The sensor is bendable because it has a thickness less than 30 µm that significantly decreases the strain. A bright fundamental mode was obtained at λ = 2.50-2.65 µm without mode distortion or scattering observed. By spectrum scanning at the -OH absorption band, the waveguide sensor was able to identify different hydroxyl compounds, such as water, methanol, and ethanol, and the concentrations of their mixtures. Real-time methanol monitoring was achieved by reading the intensity change of the waveguide mode at λ = 2.65 µm, which overlap with the stretch absorption of the hydroxyl bond. Due to the advantages of mechanical flexibility and broad mid-IR transparency, the AlN chemical sensor will enable microphotonic devices for wearables and remote biomedical and environmental detection.