Targeting HIF-1α with Specific DNA Yokes for Effective Anticancer Therapy.

Hypoxia, a ubiquitous hallmark in cancer, underscores the significance of targeting HIF-1α, the principal transcriptional factor of hypoxic responses, for effective cancer therapy. Herein, DNA yokes, a novel class of DNA nanomaterials harboring specific HIF-1α binding sequences (hypoxia response elements, HREs), are introduced as nanopharmaceuticals for cancer treatment. Comprising a basal tetrahedral DNA nanostructure and four HRE-bearing overhanging chains, DNA yokes exhibit exceptional stability and prolonged intracellular retention. The investigation reveals their capacity to bind HIF-1α, thereby disrupting its interaction with the downstream genomic DNAs and impeding transcriptional activity. Moreover, DNA yokes facilitate HIF-1α degradation via the ubiquitination pathway, thereby sequestering it from downstream targets and ultimately promoting its degradation. In addition, DNA yokes attenuate cancer cell proliferation, migration, and invasion under hypoxic conditions, while also displaying preferential accumulation within tumors, thereby inhibiting tumor growth and metastasis in vivo. This study pioneers a novel approach to cancer therapy through the development of DNA-based drugs characterized by high stability and low toxicity to normal cells, positioning DNA yokes as promising candidates for cancer treatment.

Significant response to pembrolizumab plus lenvatinib in Epstein-Barr-virus-associated intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: The prognosis for advanced intrahepatic cholangiocarcinoma (iCCA) is poor, and there remains an urgent need to develop efficient systemic therapy. The efficacy of Pembrolizumab immunotherapy combined with lenvatinibin in iCCA is still unclear. The role of Epstein-Barr-virus (EBV) as a biomarker in iCCA for response to immunotherapy needs further exploration. CASE PRESENTATION: We report a case of a 60-year-old female with EBV-associated advanced iCCA (EBVaiCCA) who progressed after first-line therapy. She accomplished an available response to the combination therapy of pembrolizumab with lenvatinib, with overall survival of 20 months. CONCLUSIONS: As far as we know, this is the first case report about the application of Pembrolizumab with lenvatinib for EBVaiCCA patients. This case indicates that the combination of immunotherapy and antiangiogenic therapy provides a glimmer of hope for advanced EBVaiCCA patients.

Can rectal MRI and endorectal ultrasound accurately predict the complete response to neoadjuvant immunotherapy for rectal cancer?

Background: Standardized assessments of clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have been established, but their utility and accuracy remain unclear. This study aimed to evaluate the clinical diagnostic value of rectal magnetic resonance imaging (MRI) and endorectal ultrasonography (ERUS) for the determination of cCRs after neoadjuvant immunotherapy and to investigate the concordance between cCR and pathological complete response (pCR). Methods: Ninety-four patients with rectal cancer treated with neoadjuvant radiotherapy with or without immunotherapy were included. The sensitivity, specificity, and accuracy of each evaluation method were calculated. Results: Combined MRI and ERUS assessments found cCR in seven of the 94 patients in our cohort. In the non-immunotherapy group, the sensitivity, specificity, and accuracy of MRI for diagnosing cCR were 50.0%, 85.2%, and 77.1%, respectively, whereas those of ERUS were 50.0%, 92.6%, and 82.9%, respectively; those of combined MRI and ERUS were 25.0%, 96.3%, and 87.5%, respectively. In the immunotherapy group, the sensitivity, specificity, and accuracy with which MRI identified CR were 51.7%, 76.7%, and 64.4%, respectively; those of ERUS were 13.8%, 90.0%, and 52.5%, respectively, and those of combined MRI and ERUS were 10.3%, 96.7%, and 54.2%, respectively. We also found that 32 of 37 patients with pCR did not meet the cCR evaluation criteria. Of these pCR patients, 78.4% (29/37) received immunotherapy. In the entire cohort, there were five pCRs among the seven cCRs. Of the four cCRs that occurred in the immunotherapy group, three were pCRs. Conclusions: Rectal MRI and/or ERUS did not provide sufficiently accurate assessments of cCR in patients with rectal cancer receiving neoadjuvant therapy, especially immunotherapy, and cCR did not predict pCR.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Hybridization chain reaction assisted multicolor immunosensor for sensitively detection of human chorionic gonadotropin.

The level of human chorionic gonadotropin (HCG) is an important indicator for early pregnancy, pregnancy-related diseases trophoblastic diseases and even cancer diagnosis. Therefore, sensitive detection of HCG has crucial significance in clinical, especially in gynaecology and obstetrics. Herein, a hybridization chain reaction (HCR) assisted multicolor immunosensor have been developed for HCG analysis. The proposed method introduced HCR after the immunoreaction between antibody and HCG protein, and produced long double strand DNA (dsDNA) that contain biotin sites. The streptavidin-horseradish peroxidase was linked on the dsDNA by the interaction between biotin and streptavidin, and can further mediated gold nanobipyramids (Au NBPs) etching. The localized surface plasmon resonance absorption peaks of Au NBPs blue shift and accompanied a vivid color change after etching effect. Based on this color change, HCG could be qualitative and semi-quantitative detected. Because of the introduction of HCR and enzyme amplification technique, the proposed method exhibited high sensitivity with a linear range of 0.1-2000 pg/mL and limit of detection (LOD) of 0.1 pg/mL. Finally, the proposed immunosensor was used to detect clinical serum samples. The results show there are no significant differences between clinical results and the test results by this method, indicating the practicability of the proposed method.

Anti-depressant medication use is a risk factor for incident knee surgery and opioid use in patients with knee osteoarthritis.

Objective: To investigate whether depression and exposure to anti-depressant medication are independent risk factors for incident knee surgery and opioid use in knee osteoarthritis (KOA) patients. Methods: We identified all patients who visited our outpatient department and were clinically diagnosed with KOA between January 2010 and January 2018. We retrieved their demographic, clinical, and radiographic data from the database of our hospital. Next, we analyzed the effect of depression and anti-depressant medication on the incident knee surgery and opioid use in KOA patients. Results: A total of 4,341 KOA patients were found eligible to form the study population. Incident knee surgery and opioid use for the purpose of treating osteoarthritis were observed in 242 and 568 patients, respectively. Incident knee surgery was significantly associated with age (OR [95%CI], 1.024 [1.009-1.039], P = 0.002), BMI (OR [95%CI], 1.090 [1.054-1.128], P < 0.001), baseline K-L grade 3 (OR [95%CI], 1.977 [1.343-2.909], P = 0.001), baseline K-L grade 4 (OR [95%CI], 1.979 [1.241-3.157], P = 0.004), depression (OR [95%CI], 1.670 [1.088-2.563], P = 0.019), and exposure to anti-depressant medication (OR [95%CI], 2.004 [1.140-3.521], P = 0.016). Incident opioid use was significantly associated with depression (OR [95%CI], 1.554 [1.089-2.215], P = 0.015) and exposure to anti-depressant medication (OR [95%CI], 1.813 [1.110-2.960], P = 0.017). Conclusion: Depression and anti-depressant drug exposure were independently associated with incident knee surgery, highlighting the need for more attention on comorbid depression in KOA management.

Effects of electroacupuncture on refractory interstitial cystitis/bladder pain syndrome: A one-year follow-up case report.

BACKGROUND: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) commonly face a decline in their quality of life and social functioning upon discontinuation of conventional therapy, which is known for its limited efficacy and the risk of relapse. While the existing evidence is somewhat restricted, acupuncture is being explored as a potential and effective treatment option for IC/BPS. CASE PRESENTATION: A 67-year-old woman, diagnosed with refractory IC/BPS, underwent treatment at the Medical Acupuncture Department of Sanming Integrated Traditional Chinese and Western Medicine Hospital. She reported symptoms of lower urinary system dysfunction, including urgency, frequency, and nocturia, along with chronic pelvic pain, and a persistent feeling of pressure and discomfort lasting over 8 years. The patient's visual analog scale (VAS) score for pelvic pain was 7 points prior to receiving acupuncture treatment. Throughout the day, she had more than 10 urinations, and at night, she urinated about once per hour. The O'Leary-Sant interstitial cystitis symptom index/interstitial cystitis problem index (ICSI/ICPI) score was 34 points, and the pelvic pain and urgency frequency (PUF) score was 19 points. RESULTS: The patient's complaints were significantly alleviated after 12 sessions of electroacupuncture treatment at BL32, BL33, BL35, and SP6 over 4 weeks. The patient claimed total relief from pelvic pain, with a VAS score of 0. The patient achieved a PUF score of 4 points and an ICSI/ICPI score of 7 points. In addition, there was a significant reduction in the frequency and urgency of urination. The patient experienced a frequency of 4-5 urinations during the day and 1-2 times at night. Subsequently, the patient's mental state and sleep quality were improved. The patient's symptoms did not change at one-year follow-up. CONCLUSION: Electroacupuncture has proven to be an effective management method for IC/BPS, as evidenced by the patient's alleviated lower urinary system symptoms and reduced pelvic pain.

Dual Self-Amplification Homogeneous Electrochemiluminescence Biosensor for Terminal Deoxynucleotidyl Transferase Activity Based on Controlling the Surface Morphology and Charge of Reporter Nanoparticles.

Terminal deoxynucleotidyl transferase (TdT) is upregulated in several types of leukemia and is considered a disease biomarker and a potential therapeutic target for leukemia. In this research, a homogeneous electrochemiluminescence (ECL) method based on the control of surface charge and morphology of tris (2,2'-bipyridine) ruthenium(II) chloride hexahydrate-doped silica nanoparticles (Ru@SiO2 NPs) has been designed for TdT activity detection. A small amount of short single-stranded DNA (ssDNA) was modified onto the surface of Ru@SiO2 NPs, and the nanoparticles with a slight positive charge experienced electrostatic attraction with the indium tin oxide (ITO) electrode with a negative charge, so relatively high ECL signals had been detected. Under the action of TdT, the ssDNA was significantly elongated, carrying numerous negative charges on its phosphate backbone, so the overall negative charge of the reporter nanoparticles was enhanced, resulting in a strong electrostatic repulsion with the ITO electrode. Simultaneously, the long ssDNA wrapped around the nanoparticles hindered the approach of the coreactant. Due to the dual effects, the ECL response of the system decreased. The constructed biosensor exhibited excellent sensitivity toward TdT over a range spanning from 1 to 100 U/L. The limit of detection is as low as 1.78 U/L. The developed approach was effectively applied to detect TdT activity in leukemic patients' leukocyte extracts.

Efficacy and safety of radiotherapy combined with anti-angiogenic therapy and immune checkpoint inhibitors in MSS/pMMR metastatic colorectal cancer.

PURPOSE: Several studies have demonstrated the effectiveness of anti-angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second-line treatment remains to be explored. METHODS: Retrospective analysis of data from mCRC patients who received anti-angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment-related deaths were reported. CONCLUSIONS: Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.

Combination of Multiple MRI Parameters Related to Signal Intensity and Volume for Predicting Response to Neoadjuvant Chemoradiotherapy by Patients with Locally Advanced Rectal Cancer.

BACKGROUND: MRI of patients with locally advanced rectal cancer (LARC) can predict the pathological complete response (pCR) to preoperative chemoradiation therapy (CRT). Our purpose was to use MRI results to evaluate the diagnostic value of combined changes in signal intensity (SI) and volume (V) of patients with LARC for predicting pCR to CRT. METHODS: This retrospective study on 100 patients with LARC analyzed clinical and imaging data that were collected from March, 2018, to March, 2020. Before and after CRT, T2-weighted (T2W), apparent diffusion coefficient (ADC), and contrast-enhanced T1-weighted (ceT1W) data were analyzed. Percent changes of V (%#916;V) and relative SI ratio (%#916;SIR) on different sequences were calculated. After CRT, patients had pathological confirmation as pCR or non-pCR. Data were analyzed using nonparametric tests and receiver operating characteristic (ROC) analysis. RESULTS: There were 34 pCR and 66 non-pCR patients. Except for ADC-%#916;SIR, the combined parameters and single parameters had a greater decrease in the pCR group. The combination of ADC-%#916;V and T2W-%#916;SIR had the greatest diagnostic value (AUC=0.85,cutoff=0.23%) and the combination of ADC-%ΔV% and #916;SIR had the best accuracy (89%, cutoff=44.11%). Except for T2W-%#916;V and T2W-%#916;SIR, the different sequences had moderate differences in diagnostic performance. The diagnostic performance of combined parameters or single parameters on ADC and T2W was significantly better than those on ceT1W (p#916;60;0.01). CONCLUSION: All sequences except ADC-%#916;SIR provided reliable predictions of pCR, although ceT1W data had limited usefulness.

Dual-Signal Mode Ratiometric Photoelectrochemical Sensor Based on G-Quadruplex Hole Transport for Rapid and Sensitive Detection of miRNA-210.

For rapid and sensitive detection of miRNA-210, which is important for improving the reliability of clinical diagnosis of breast cancer, a dual-signal mode ratiometric photoelectrochemical (PEC) sensor based on a Au/GaN photoanode is proposed. First, a DNA probe was designed that could complement the target miRNA-210. Then, another G-rich DNA sequence was designed to mismatch the probe and form a double-stranded DNA (dsDNA). Upon addition of the target, the dsDNA unwinds from its binding site and releases G-rich single-stranded DNA. In the presence of Mg2+ and K+, this single-stranded DNA molecule spontaneously forms a G-quadruplex structure, facilitating the rapid transport of photogenerated holes, thereby increasing the photocurrent response of Au/GaN and enabling sensitive label-free detection of miRNA-210. By control of different pH values, a response signal was generated at pH 8, while a reference signal was produced at pH 5. The designed PEC system shows a high potential for the development of miRNA-210 detection. Ultimately, the response signal-to-reference signal ratio was used as the variable, and a broad linear span ranging from 10 fM to 1 nM (R2 = 0.993) has been exhibited, with a detection threshold of 3 fM (S/N = 3). The designed PEC platform shows potential for the development of other disease markers.

Alcoholic drink produced by pea is a risk factor for incident knee surgery in patients with knee osteoarthritis.

Objective: The objective of this study is to investigate whether alcohol exposure and specific alcoholic drinks are independent risk factors for incident knee surgery in knee osteoarthritis (KOA) patients. Methods: We identified all patients who were clinically diagnosed as KOA between January 2010 and January 2018 in our outpatient department. Demographic, clinical, and radiographic data were collected from the database of our hospital. Next, we analyzed the association between alcohol consumption and incident knee surgery. Results: A total of 4,341 KOA patients completed the current study and were included in the final analysis. Incident knee surgery for the purpose of treating osteoarthritis was observed in 242 patients. Incident knee surgery was significantly associated with age (OR [95%CI], 1.023 [1.009-1.039], P = 0.002), BMI (OR [95%CI], 1.086 [1.049-1.123], P < 0.001), baseline K-L grade 3 (OR [95%CI], 1.960 [1.331-2.886], P = 0.001), baseline K-L grade 4 (OR [95%CI], 1.966 [1.230-3.143], P = 0.005), 7.1-14 drinks per week (OR [95%CI], 2.013 [1.282-3.159], P = 0.002), >14 standard drinks per week (OR [95%CI], 2.556 [1.504-4.344], P = 0.001), and the most common alcoholic drink produced by pea (OR [95%CI], 3.133 [1.715-5.723], P < 0.001). Conclusion: KOA patients who consumed more than seven standard drinks per week were at substantial risk of incident knee surgery. In addition, alcoholic drink produced by pea is also an independent risk factor.

Highly specific and sensitive sandwich-type electrochemiluminescence biosensor for HPV16 DNA detection based on the base-stacking effect and bovine serum albumin carrier platform.

The detection of specific DNA sequences and the identification of single nucleotide polymorphisms are important for disease diagnosis. Herein, by combining the high specificity of the base-stacking effect with the high reproducibility of bovine serum albumin (BSA) modified electrodes and the high loading performance of DNA nanoclews (DNA NCs), a novel sandwich-type electrochemiluminescence (ECL) biosensor is reported for the highly specific detection of HPV16 (chosen as the model target). The capture probes are loaded by BSA carrier platforms modified on the gold electrode surface to improve reproducibility. DNA NCs loaded with a large amount of Ru(phen)32+ worked as signal probes. The template probe is composed of the complementary strand of the target and two free nucleic acid anchors at the head and tail. In the presence of the target DNA, the template probes can form stacked base pairs with target, generating high base-stacking energy. This results in the shorter free anchors of template probes being able to bind to the capture and signal probes. This eventually forms a sandwich structure that allows Ru(phen)32+ to be near the electrode surface, producing an ECL signal. There is a linear relationship between the signal and the target concentration range from 10 fM to 100 pM, with a detection limit of 5.03 fM (S/N=3). Moreover, the base-stacking effect has single base recognition ability for base pairs, effectively avoiding false positive signals. The results of this strategy for clinical samples are consistent with classical methods.

FAM3 family genes are associated with prognostic value of human cancer: a pan-cancer analysis.

Family with sequence similarity three member (FAM3) plays a crucial role in the malignant development of various cancers of human. However, there remains doubtful what specific role of FAM3 family genes in pan-cancer. Our study aimed to investigate the role of FAM3 family genes in prognosis, immune subtype, tumor immune microenvironment, stemness score, and anticancer drug sensitivity of pan-cancer. We obtained data from UCSC Xena GDC and CellMiner databases, and used them to study the correlation of the expression, survival, immune subtype, tumor microenvironment, stemness score, and anticancer drug sensitivity between FAM3 family genes with pan-cancer. Furthermore, we investigated the tumor cellular functions and clinical prognostic value FAMC3 in pancreatic cancer (PAAD) using cellular experiments and tissue microarray. Cell Counting Kit-8 (CCK-8), transwell invasion, wound-healing and apoptosis assays were performed to study the effect of FAM3C on SW1990 cells' proliferation, migration, invasion and apoptosis. Immunohistochemical staining was used to study the relationship between FAM3C expression and clinical characteristics of pancreatic cancer patients. The results revealed that FAM3 family genes are significantly differential expression in tumor and adjacent normal tissues in 7 cancers (CHOL, HNSC, KICH, LUAD, LUSC, READ, and STAD). The expression of FAM3 family genes were negatively related with the RNAss, and robust correlated with immune type, tumor immune microenvironment and drug sensitivity. The expression of FAM3 family genes in pan-cancers were significantly different in immune type C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet), and C6 (TGF-beta dominant). Meanwhile, overexpression FAM3C promoted SW1990 cells proliferation, migration, invasion and suppressed SW1990 cells apoptosis. While knockdown of FAM3C triggered opposite results. High FAM3C expression was associated with duodenal invasion, differentiation and liver metastasis. In summary, this study provided a new perspective on the potential therapeutic role of FAM3 family genes in pan-cancer. In particular, FAM3C may play an important role in the occurrence and progression of PAAD.

Pretreatment high cholesterol and low neutrophils predict complete pathological response after neoadjuvant short­course radiotherapy followed by chemotherapy and immunotherapy in locally advanced rectal cancer.

The present study was aimed at looking for hematological indicators that could predict pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with short-course radiotherapy (SCRT) followed by chemotherapy and immunotherapy. A total of 171 patients were enrolled in this observational retrospective study. Pretreatment values of albumin, total cholesterol, lactate dehydrogenase, neutrophil, platelet and lymphocytes were available. Univariate and multivariate logistics analyses were used to determine the prognostic factor for pCR. SCRT followed by chemotherapy and immunotherapy was demonstrated to double the pCR rate (50.5%) compared with long-course chemoradiotherapy. For the former group, baseline high platelet to lymphocyte ratio (P=0.047), high cholesterol (P=0.026) and low neutrophils (P=0.012) level were associated with high pCR rate and baseline high cholesterol (P=0.016) and low neutrophils (P=0.020) level were the independent prognostic factors for pCR. In conclusion, pretreatment high cholesterol and low neutrophils were the independent prognostic predictors of pCR in patients with LARC treated with SCRT followed by chemotherapy and immunotherapy. Clinical trial no. NCT04928807, June 16, 2021.

Ultrasensitive photoelectrochemical detection of glutathione based on the multifunctional catalytic properties of phosphotungstic acid.

A novel photoelectrochemical (PEC) sensor was constructed for the highly sensitive detection of reduced glutathione (GSH) based on the multiple catalytic properties of phosphotungstic acid (PTA). In this work, the catalytic properties of PTA were applied to PEC sensing for the first time and interpreted in detail. First, PTA as an electron acceptor can inhibit the complexation of photogenerated electron-hole pairs in p-Cu2O, thus significantly increasing the photogenerated current of p-type semiconductor material Cu2O. Secondly, when GSH is oxidized to oxidized glutathione (GSSG) by photogenerated holes on the photocathode, PTA is able to reduce GSSG to GSH by transferring protons, forming a redox cycle regeneration process of GSH. Finally, the relatively large amount of PTA in the background solution was able to pre-oxidize interfering substances such as L-cysteine and ascorbic acid, which improved the selectivity of the method. Under the optimal experimental conditions, the linear range of the PEC sensor response to GSH was 0.050-100 nmol L-1, with a detection limit as low as 0.017 nmol L-1 (S/N = 3), which can be applied to the detection of GSH content in cell lysate samples.

Electrochemiluminescence Biosensor for Estrogen-Related Receptor Alpha (ERRα) Based on Target-Induced Change of the Steric Hindrance Effect of an Antibody-Modified Electrode.

In this work, a simple and sensitive electrochemiluminescence (ECL) biosensor has been devised based on target-induced steric hindrance of an antibody-modified electrode surface. Estrogen-related receptor alpha (ERRα) is closely related to estrogen-dependent tumors, which had been chosen as a model target. The ERRα antigen can bind to the antibody modified on the electrode surface with high specificity and results in the increase of steric hindrance, which prevented the ECL indicators (tris(2,2'-bipyridine) dichlororuthenium(II) hexahydrate) from approaching the electrode surface, and the ECL intensity of the system decreased. The ECL response of the system has a good linear relationship with ERRα concentration in the range of 1.0-60 ng/L, and the limit of detection is 0.5 ng/L. Different from the traditional sandwiched immune ECL detection system, which need the modification of ECL indicators on the secondary antibody, only one antibody had been used in this system. The system is easy to operate and has good sensitivity. The designed biosensor has been applied to detect ERRα in the serum and different cell line samples with satisfied results.

Rapid on-site detection of underground petroleum pipeline leaks and risk assessment using portable gas chromatography-mass spectrometry and solid phase microextraction.

Locating underground pipeline leaks can be challenging due to their hidden nature and variable terrain conditions. To sample soil gas, solid-phase microextraction (SPME) was employed, and a portable gas chromatography/mass spectrometry (GC/MS) was used to detect the presence and concentrations of petroleum hydrocarbon volatile organic compounds (pH-VOCs), including benzene, toluene, ethylbenzene, and xylene (BTEX). We optimized the extraction method through benchtop studies using SPME. The appropriate fibre materials and exposure time were selected for each BTEX compound. Before applying SPME, we preconditioned the soil vapour samples by keeping the temperature at around 4 °C and using ethanol as a desorbing agent and moisture filters to minimize the impact of moisture. To conduct this optimisation, airbags were applied to condition the soil vapour samples and SPME sampling. By conditioning the samples using this method, we were able to improve analytical efficiency and accuracy while minimizing environmental impacts, resulting in more reliable research data in the field. The study employed portable GC/MS data to assess the concentration distribution of BTEX in soil vapour samples obtained from 1.5 m below the ground surface at 10 subsurface vapour monitoring locations at the leak site. After optimization, the detection limits of BTEX were almost 100 µg/m3, and the measurement repeatabilities were approximately 5% and 15% for BTEX standards in the laboratory and soil vapour samples in the field, respectively. The soil vapour samples showed a hotspot region with high BTEX concentrations, reaching 30 mg/m3, indicating a diesel return pipeline leak caused by a gasket failure in a flange. The prompt detection of the leak source was critical in minimizing environmental impact and worker safety hazards.

Review and Perspective: Gas Separation and Discrimination Technologies for Current Gas Sensors in Environmental Applications.

Presently, numerous state-of-the-art approaches are being adapted for gas sensing and monitoring. These include hazardous gas leak detection as well as ambient air monitoring. Photoionization detectors, electrochemical sensors, and optical infrared sensors are a few of the commonly widely used technologies. Extensive reviews on the current state of gas sensors have been summarized. These sensors, which are either nonselective or semiselective, are affected by unwanted analytes. On the other hand, volatile organic compounds (VOCs) can be heavily mixed in many vapor intrusion situations. To determine the individual VOCs in a highly mixed gas sample using nonselective or semiselective gas sensors, gas separation and discrimination technologies are highly warranted. These technologies include gas permeable membranes, metal-organic frameworks, microfluidics and IR bandpass filters for different sensors, respectively. The majority of these gas separation and discrimination technologies are currently being developed and evaluated in laboratory-controlled environments and have not yet been extensively utilized in the field for vapor intrusion monitoring. These technologies show promise for continued development and application in the field for more complex gas mixtures. Hence, the present review focuses on the perspectives and a summary of the existing gas separation and discrimination technologies for the currently popular reported gas sensors in environmental applications.

A deep learning model for lymph node metastasis prediction based on digital histopathological images of primary endometrial cancer.

Background: The current study aimed to develop a deep learning (DL) model for prediction of lymph node metastasis (LNM) based on hematoxylin and eosin (HE)-stained histopathological images of endometrial cancer (EC). The model was validated using external data. Methods: A total of 2,104 whole slide image (WSI) from 564 patients with pathologically confirmed LNM status were collated from West China Second University Hospital. An artificial intelligence (AI) model was built on the multiple instance-learning (MIL) framework for automatic prediction of the probability of LNM and its performance compared with "Mayo criteria". An additional external data source comprising 533 WSI was collected from two independent medical institutions to validate the model's robustness. Heatmaps were generated to demonstrate regions of the WSI that made the greatest contributions to the DL network output to improve understanding of these processes. Results: The proposed MIL model achieved an area under the curve (AUC) of 0.938, a sensitivity of 0.830 and a specificity of 0.911 for LNM prediction to EC. The AUC according to Mayo criteria was 0.666 for the same test dataset. For types I, II and mixed EC, AUCs were 0.927, 0.979 and 0.929, respectively. The predictive performance of the MIL model also achieved an AUC of 0.921 for early staging. In external validation data, the proposed model achieved an AUC of 0.770, a sensitivity of 0.814 and a specificity of 0.520 for LNM prediction. AUCs were 0.783 for type I and 0.818 for early stage EC. Conclusions: The proposed MIL model generated from histopathological images of EC has a much better LNM predictive performance than that of Mayo criteria. A novel DL-based biomarker trained on different histological subtypes of EC slides was revealed to predict metastatic status with improved accuracy, especially for early staging patients. The current study proves the concept of MIL-based prediction of LNM in EC for the first time, and brought a new sight to improve the accuracy of LNM prediction. Multicenter prospective validation data is required to further confirm the clinical utility.