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Therapeutic drug monitoring is essential for dosing pharmaceuticals with narrow therapeutic windows. Nevertheless, standard methods are imprecise and involve invasive/resource-intensive procedures with long turnaround times. Overcoming these limitations, we present a microneedle-based electrochemical aptamer biosensing patch (μNEAB-patch) that minimally invasively probes the interstitial fluid (ISF) and renders correlated, continuous, and real-time measurements of the circulating drugs' pharmacokinetics. The μNEAB-patch is created following an introduced low-cost fabrication scheme, which transforms a shortened clinical-grade needle into a high-quality gold nanoparticle-based substrate for robust aptamer immobilization and efficient electrochemical signal retrieval. This enables the reliable in vivo detection of a wide library of ISF analytes-especially those with nonexistent natural recognition elements. Accordingly, we developed μNEABs targeting various drugs, including antibiotics with narrow therapeutic windows (tobramycin and vancomycin). Through in vivo animal studies, we demonstrated the strong correlation between the ISF/circulating drug levels and the device's potential clinical use for timely prediction of total drug exposure.

The awareness of individuals’ biological status is critical for creating interactive and adaptive environments that can actively assist the users to achieve optimal outcomes. Accordingly, specialized human–machine interfaces—equipped with bioperception and interpretation capabilities—are required. To this end, we devised a multimodal cryptographic bio-human–machine interface (CB-HMI), which seamlessly translates the user’s touch-based entries into encrypted biochemical, biophysical, and biometric indices. As its central component, the CB-HMI features thin hydrogel-coated chemical sensors and inference algorithms to noninvasively and inconspicuously acquire biochemical indices such as circulating molecules that partition onto the skin (here, ethanol and acetaminophen). Additionally, the CB-HMI hosts physical sensors and associated algorithms to simultaneously acquire the user’s heart rate, blood oxygen level, and fingerprint minutiae pattern. Supported by human subject studies, we demonstrated the CB-HMI’s capability in terms of acquiring physiologically relevant readouts of target bioindices, as well as user-identifying and biometrically encrypting/decrypting these indices in situ (leveraging the fingerprint feature). By upgrading the common surrounding objects with the CB-HMI, we created interactive solutions for driving safety and medication use. Specifically, we demonstrated a vehicle-activation system and a medication-dispensing system, where the integrated CB-HMI uniquely enabled user bioauthentication (on the basis of the user’s biological state and identity) prior to rendering the intended services. Harnessing the levels of bioperception achieved by the CB-HMI and other intelligent HMIs, we can equip our surroundings with a comprehensive and deep awareness of individuals’ psychophysiological state and needs.

With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.

Active biofluid management is central to the realization of wearable bioanalytical platforms that are poised to autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, here, a programmable epidermal microfluidic valving system is devised, which is capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. At its core, the system is a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system is harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection). Through integration with a wireless flexible printed circuit board and seamless bilateral communication with consumer electronics (e.g., smartwatch), contextually-relevant (scheduled/on-demand) on-body biomarker data acquisition/display was achieved.

To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. In that regard, wearable biosensing technologies, capable of tracking drug pharmacokinetics in noninvasively retrievable biofluids (e.g., sweat), play a critical role, because they can be deployed at a large scale to monitor the individuals' drug transcourse profiles (semi)continuously and longitudinally. To this end, voltammetry-based sensing modalities are suitable, as in principle they can detect and quantify electroactive drugs on the basis of the target's redox signature. However, the target's redox signature in complex biofluid matrices can be confounded by the immediate biofouling effects and distorted/buried by the interfering voltammetric responses of endogenous electroactive species. Here, we devise a wearable voltammetric sensor development strategy-centering on engineering the molecule-surface interactions-to simultaneously mitigate biofouling and create an "undistorted potential window" within which the target drug's voltammetric response is dominant and interference is eliminated. To inform its clinical utility, our strategy was adopted to track the temporal profile of circulating acetaminophen (a widely used analgesic and antipyretic) in saliva and sweat, using a surface-modified boron-doped diamond sensing interface (cross-validated with laboratory-based assays, R 2 ∼ 0.94). Through integration of the engineered sensing interface within a custom-developed smartwatch, and augmentation with a dedicated analytical framework (for redox peak extraction), we realized a wearable solution to seamlessly render drug readouts with minute-level temporal resolution. Leveraging this solution, we demonstrated the pharmacokinetic correlation and significance of sweat readings.

Negative lattice expansion-induced upconversion luminescence (UCL) thermal enhancement can be used to efficiently solve the problems of thermal quenching of lanthanide ions, and it can be combined with traditional fluorescence intensity ratio technology to obtain temperature-sensing characteristics. In this work, linear negative thermal expansion of the lattice of Na2MoO4:Yb3+, Er3+ transparent glass ceramics was examined after fabrication by a low-temperature co-sintering approach. Thermal enhancement of UCL at 525 and 806/860 nm for the glass ceramics was caused by an increase in energy transfer between Yb3+ and Er3+ ions induced by the linear negative thermal expansion properties of orthorhombic Na2MoO4 nanoparticles. Combining the UCL characteristics of a positive thermal expansion tellurite glass matrix and negative thermal expansion Na2MoO4:Yb3+, Er3+ nanoparticles, a novel glass ceramic temperature sensor was obtained. The temperature relative sensitivity was manipulated by selecting different UCL spectral modes up to 3.14% K−1 (313 K), which provided a more optimal performance than many glass ceramics previously reported. The cycle measurement of the UCL response alternating between 313 and 573 K indicates excellent repeatability, and thus, there is the potential for successful application of Na2MoO4:Yb3+, Er3+ transparent glass ceramics as a new generation of temperature sensors. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is a common tumor malignancy of the endocrine system worldwide. Recently, circular RNAs (circRNAs) have been reported to participate in diverse pathological processes, especially in tumorigenesis. However, the functional role and mechanism of circRNA pleckstrin and Sec7 domain containing 3 (circ-PSD3) in PTC are still unclear. In this study, qRT-PCR results showed that circ-PSD3 was significantly upregulated in PTC tissues and cell lines. Meanwhile, circ-PSD3 overexpression was positively associated with larger tumor size, TNM stage, and lymph node metastasis. Knockdown of circ-PSD3 suppressed the proliferation and invasion of PTC cells. Besides, circ-PSD3 interacted with miR-7-5p to reduce its expression, and methyltransferase like 7B (METTL7B) was verified as a target gene of miR-7-5p. Functionally, inhibition of circ-PSD3 impeded PTC cell proliferation and invasion via targeting miR-7-5p to downregulate METTL7B expression. Taken together, silencing of circ-PSD3 hampered the proliferation and invasion of PTC cells via upregulating the inhibitory effect of miR-7-5p on METTL7B expression. Therefore, circ-PSD3 could be a potential diagnostic biomarker or molecular treatment target for PTC. [ABSTRACT FROM AUTHOR]

Photoluminescence (PL) of rare earth ion‐doped glasses could be enhanced by diverse Ag species such as Ag+ ions, Ag+‐Ag+ pairs, Ag nano‐clusters (NCs), and Ag nanoparticles (NPs). Selective preparation of silver species in rare earth ion‐doped glasses is a crucial step to obtain the luminescence enhancement of rare earth ions caused by the different silver species. In this work, Ag+ ions and Ag NCs were selectively prepared in the Sm3+‐doped borosilicate glass via the Ag+‐Na+ ion exchange. The influence of AgNO3/NaNO3 ratio in the molten salt on the Ag existing states was investigated. The results demonstrate that the isolated Ag+ ions exist in the Sm3+‐doped borosilicate glass when the ratio of AgNO3/NaNO3 is 1/1000. The Ag NCs are formed in the Sm3+‐doped borosilicate glass when the AgNO3/NaNO3 ratio is 1/10. The influence of Ag+ ions or Ag NCs on the PL of Sm3+ was systematically investigated. The results show that the PL of Sm3+ was enhanced by the energy transfer from Ag+ ions or Ag NCs to Sm3+. [ABSTRACT FROM AUTHOR]

Considering the resistance of papillary thyroid cancer (PTC) 131I therapy, this study was designed to find a solution at molecular respect. By probing into lncRNA-NEAT1/miR-101-3p/FN1 axis and PI3K/AKT signaling pathway, this study provided a potential target for PTC therapy. 131I-resistant cell lines were established by continuous treatment with median-lethal 131I. Bioinformatic analysis was applied to filtrate possible lncRNA/miRNA/mRNA and related signaling pathway. Luciferase reporter assay was employed in the verification of the targeting relationship between lncRNA and miRNA as well as miRNA and mRNA. MTT assay and flow cytometry assay were performed to observe the impact of NEAT1/miR-101-3p/FN1 on cell viability and apoptosis in radioactivity iodine (RAI)-resistant PTC cell lines, respectively. Western blot and qRT-PCR were conducted to measure the expression of proteins and mRNAs in RAI-resistant PTC tissues and cells. Meanwhile, endogenous PTC mice model were constructed, in order to verify the relation between NEAT1 and RAI-resistance in vivo. NEAT1 was over-expressed in RAI-resistant PTC tissues and cell lines and could resist RAI by accelerating proliferation accompanied by suppressing apoptosis. It indicated that overexpressed NEAT1 restrained the damage of RAI to tumor in both macroscopic and microcosmic. Besides, NEAT1/miR-101-3p exhibited a negative correlation by directly targeting each other. The expression of FN1, an overexpressed downstream protein in RAI-resistance PTC tissues, could be tuned down by miR-101-3p, while the decrease could be restored by NEAT1. In conclusion, both in vitro and in vivo, NEAT1 suppression could inhibit 131I resistance of PTC by upregulating miR-101-3p/FN1 expression and inactivated PI3K/AKT signaling pathway both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

A vast amount of evidence indicates that long non-coding RNAs (lncRNAs) are involved in cancer. Previous studies have indicated that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) is aberrantly expressed in lung cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma. However, the role of DGCR5 in papillary thyroid carcinoma (PTC) has remained elusive. In the present study, it was revealed that DGCR5 was significantly downregulated in PTC tissues compared with that in adjacent normal tissues. Through functional experiments, it was demonstrated that ectopic overexpression of DGCR5 markedly suppressed PTC cell growth and invasion. A bioinformatics analysis suggested that DGCR5 binds to microRNA (miR)-2861. A total of 5 putative binding sites for miR-2861 were identified in DGCR5, and a luciferase reporter assay confirmed the direct interaction between DGCR5 and miR-2861. Furthermore, reverse transcription-quantitative polymerase chain reaction analysis indicated that ectopic overexpression of DGCR5 led to a decreased expression of miR-2861 in PTC cells and miR-2861 mimic transfection caused a downregulation of DGCR5. miR-2861 level was upregulated in PTC tissues compared with adjacent tissues and negatively correlated with DGCR5 level. In addition, rescue experiments indicated that ectopic expression of miR-2861 reversed the effects of DGCR5 overexpression on PTC cell proliferation and invasion. Taken together, the present results demonstrated that DGCR5 inhibits PTC progression via sponging miR-2861, indicating DGCR5 may serve as a therapeutic target. [ABSTRACT FROM AUTHOR]

Thyroid carcinoma is primarily treated by surgery combined with radioactive 131iodine (131I) treatment; however, certain patients exhibit resistance to 131I treatment. Previous research indicated that nuclear factor‑κB (NF‑κB) was associated with resistance to 131I in cancer cells. The present study aimed to investigate the effects of NF‑κB on 131I uptake and apoptosis in thyroid carcinoma cells. TPC‑1 and BCPAP cell lines were employed as research models in the present study, and the expression of NF‑κB was inhibited by RNA interference (RNAi). The ability of TPC‑1 and BCPAP cells to uptake 131I was measured and the cell viability was detected by an MTT assay. Finally, the expression of the apoptosis‑associated proteins X‑linked inhibitor of apoptosis (XIAP), cellular inhibitor of apoptosis protein 1 (cIAP1) and caspase‑3 in TCP‑1 and BCPAP cells was determined by western blotting. Western blotting results demonstrated that the expression levels of NF‑κB in TPC‑1 and BCPAP cells were successfully downregulated by RNAi (P<0.05), while analysis of 131I uptake revealed no significant alterations in the 131I uptake ability of cells following RNAi (P>0.05). MTT experiments demonstrated that the inhibition of NF‑κB expression in combination with radiation (131I treatment) led to a marked reduction in cell viability (P<0.05). Furthermore, western blot analysis revealed that the inhibition of NF‑κB expression downregulated the expression levels of XIAP and cIAP1 (P<0.05), while the expression levels of caspase‑3 were upregulated, indicating that the observed reduction in cell viability following NF‑κB inhibition may be due to an increased level of apoptosis. Although NF‑κB inhibition did not affect the 131I uptake of thyroid cancer cells, this inhibition may increase the apoptotic effects of radioactive 131I. [ABSTRACT FROM AUTHOR]

Abstract: Upconversion inverse opal photonic crystals based on a luminescent matrix of Yb, Er co-doped Y2Ti2O7 were synthesized, and their photoluminescence was investigated. By comparing the spectra of the inverse opals with that of the reference sample, the contribution of photonic band gap effect to the upconversion emission was observed in the Y2Ti2O7: Yb, Er inverse opals. Intensity of the green or red upconversion emission from Er3+ was depressed when the overlapping between the photonic band-gap and Er3+ ions emission band occurs. [Copyright &y& Elsevier]