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Covalent organic frameworks (COFs) have demonstrated versatile application potential since their discovery. Although the structure of COFs is orderly arranged, the synthesis of controllable macrostructures still faces challenges. Herein, we report, to our knowledge, the first template-free self-assembled COF-18 Å hollow microtubule (MT-COF-18 Å) structure and its use for insulin delivery that exhibits high loading capacity, gastroresistance, and glucose-responsive properties. The hollow MT-COF-18 Å was achieved by a template-free method benefiting from the mixed solvents of mesitylene and dioxane. The formation mechanism and morphology changes with insulin loading and release were observed. In Caco-2 cells, the transferrin-coated system demonstrated enhanced insulin cellular uptake and transcellular transport, which indicated great potential for oral applications. Additionally, the composites presented sustained glycemic control and effective insulin blood concentrations without noticeable toxicity in diabetic rats. This work shows that hollow microtubular COFs hold great promise in loading and delivery of biomolecules.

IMPORTANCE: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor–related bone metastases. OBJECTIVES: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor–related bone metastases based on a large-scale head-to-head study. DESIGN, SETTING, AND PARTICIPANTS: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. INTERVENTIONS: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. MAIN OUTCOMES AND MEASURES: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). RESULTS: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was −72.0% (95% CI, −73.5% to −70.4%) in the MW032 group and −72.7% (95% CI, −74.2% to −71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of −1.27 and −1.30, or a difference of 0.02. The 90% CI for the difference (−0.04 to 0.09) was within the equivalence margin (−0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, −0.06 to 0.09), −0.02 (95% CI, −0.09 to 0.06), −0.05 (95% CI, −0.13 to 0.03) and 0.001 (95% CI, −0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were −0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, −0.07 to 0.07), −0.085 (95% CI, −0.18 to 0.01), −0.09 (95% CI, −0.20 to 0.02), and −0.13 (95% CI, −0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (−1.4%; 95% CI, −5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. CONCLUSIONS AND RELEVANCE: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812509

Pyroptosis has been reported to improve the antitumor effect by evoking a more intense immune response and a therapeutic effect. For phototherapy, several photosensitizers have been found to initiate pyroptosis. However, the effect of pyroptosis associated with apoptosis in enhancing the antitumor therapy needs sufficient characterization, especially under long-term treatment. As a NIR photosensitizer, heptamethine cyanines have been discovered for anticancer phototherapy for deep tissue penetration and inherent tumor-targeted capability. However, they are not quite stable for long-term performance. To investigate the effect of pyroptosis along with apoptosis on the anticancer immune responses and phototherapy, here, we chemically modulate the cyanine IR780 to regulate hydrophobicity, stability, and intracellular targeting. Two photosensitizers, T780T-TPP and T780T-TPP-C12, were finally optimized and showed excellent photostability with high photothermal conversion efficiency. Although the cellular uptake of the two molecules was both mediated by OATP transporters, T780T-TPP induced tumor cell death via pyroptosis and apoptosis and accumulated in tumor accumulation, while T780T-TPP-C12was prone to accumulate in the liver. Ultimately, via one injection-multiple irradiation treatment protocol, T780T-TPP displayed a significant antitumor effect, even against the growth of large tumors (200 mm3).

Precise profiling of the cytokine panel consisting of different levels of cytokines can provide personalized information about several diseases at certain stages. In this study, we have designed and fabricated an “all-in-one” diagnostic tool kit to bioassay multiple inflammatory cytokines ranging from picograms per milliliter to μg/mL in a small cytokine panel. Taking advantage of the kit fabricated by the DNA-encoded assembly of nanocatalysts in dynamic regulation and signal amplification, we have demonstrated the multiplex, visual, and quantitative detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) with limits of detection of 1.6 ng/mL (61.54 pM), 20 pg/mL (1.57 pM), and 4 pg/mL (0.19 pM), respectively. This diagnostic tool kit can work well with commercial kits for detecting serum cytokines from breast cancer patients treated with immunotherapies. Furthermore, a small cytokine panel composed of CRP, PCT, and IL-6 is revealed to be significantly heterogeneous in each patient and highly dynamic for different treatment courses, showing promise as a panel of quantitative biomarker candidates for individual treatments. So, our work may provide a versatile diagnostic tool kit for the visual detection of clinical biomarkers with an adjustable broad detection range.

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n= 353; experimental arm) versus placebo and nab-P (n= 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470–0.906, P= 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414–0.914, P= 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579.

Recently, nanoformulations have been widely applied in the delivery of organic photothermal agents (OPTAs) for cancer therapy to prolong blood circulation or improve tumor-targeting capacity. However, the systematic evaluations of their effects on the photothermal behavior of OPTAs are limited, especially for different types of nanoparticle systems. Herein, we prepared two kinds of nanoparticles (BSA and PEG nanoparticles (NPs)) to load an OPTA, a cyanine photosensitizer (IR780-O-TPE), and investigated their photothermal response, organelle targeting, and in vivo therapeutic efficacy. Due to different assembly forms, the two NPs showed distinct morphological changes after exposure to laser or hyperthermia. Under laser irradiation at 808 nm, BSA NPs could release IR780-O-TPE more efficiently than PEG NPs. We speculate that this phenomenon is probably caused by dual-responsive release of IR780-O-TPE from BSA NPs against light and hyperthermia. Moreover, IR780-O-TPE/BSA NPs were highly mitochondria-targeting and therefore displayed significant inhibition of cell viability. In contrast, IR780-O-TPE/PEG NPs were “shell–core” nanostructures and more stable under laser stimulation. As a consequence, the mitochondria-targeting and anticancer photothermal therapy by IR780-O-TPE/PEG NPs was less obvious. This study revealed the significance of nanocarrier design for OPTA delivery and demonstrated that BSA NPs could release IR780-O-TPE more effectively for efficient photothermal therapy. We also believe that the dual-responsive release of OPTAs from NPs can provide an effective strategy to promote anticancer photothermal treatment.

With the rapid development of nanotechnology, researchers have designed a variety of intelligent nanodelivery systems to enhance tumor targeting of anticancer drugs. However, increased tumor accumulation does not indicate deeper penetration in the tumor tissue, without which the tumor cells in the core area cannot be sufficiently killed. Herein, we develop a size-controllable nanoparticle system for deep-penetrating cancer therapy, which will be programmably disassembled with the decrease of the pH from the normal tissue to the tumor microenvironment and to the intracellular area. The integrated nanoparticle is composed of a gold nanoparticle (GNP, ∼30 nm) and a tetrahedral DNA nanostructure (TDN, ∼25 nm) loaded with doxorubicin (DOX). Initially, the nanoparticles maintain a larger size (∼100 nm) to accumulate in the tumor through the enhanced permeability and retention effect. At a pH of about 6.5 at the tumor microenvironment, with the linkage of DNA sequences converting into a triplex structure, the TDNs detach from the GNP and penetrate deeply into the tumor interstitium and then are internalized into the cells. Finally, in acidic lysosomes with pH 5.0, the TDNs release DOX by forming an i-motif structure. This nanosmart delivery system thus shows effective deep penetration into the tumor core with good antitumor efficacy and satisfactory biocompatibility and provides new insights into the development of intelligent nanosystems for anti-cancer treatment.

Blockade of the cyclin-dependent kinase 4 and 6 pathway has been shown to be effective in the treatment of hormone receptor-positive advanced breast cancer (ABC). We report the interim results of DAWNA-1 (NCT03927456), a double-blind, randomized, phase 3 trial of dalpiciclib (a new cyclin-dependent kinase 4 and 6 inhibitor) plus fulvestrant in hormone receptor-positive, HER2-negative ABC with disease progression after endocrine therapy. A total of 361 patients were randomized 2:1 to receive dalpiciclib plus fulvestrant or placebo plus fulvestrant. The study met the primary end point, showing significantly prolonged investigator-assessed progression-free survival with dalpiciclib plus fulvestrant versus placebo plus fulvestrant (median = 15.7, 95% confidence interval (CI) = 11.1–not reached versus 7.2, 95% CI = 5.6–9.2 months; hazard ratio = 0.42, 95% CI = 0.31–0.58; one-sided P< 0.0001 (boundary was P ≤ 0.008)). The most common grade 3 or 4 adverse events with dalpiciclib plus fulvestrant were neutropenia (84.2%) and leukopenia (62.1%). The incidence of serious adverse events was 5.8% with dalpiciclib plus fulvestrant versus 6.7% with placebo plus fulvestrant. Our findings support dalpiciclib plus fulvestrant as a new treatment option for pretreated hormone receptor-positive, HER2-negative ABC.

Phenotypic plasticity is an emerging paradigm for providing biological and clinical insights into cancer initiation, progression, and resistance to therapy. However, it is a great challenge to track phenotypic information on live cells with high levels of sensitivity, specificity, and simplicity, when a specific cancer-cell subset is being targeted. In this work, we have successfully achieved cascade assembly of nanoparticles on the surface of specific cancer cells by designing a dual-aptamer-weaved molecular AND logic system. Taking advantage of spatial addressability, precise controllability, and targeting recognition of the nanostructure assemblies, we can precisely label the target-cell subset in a large population of similar cells and rapidly obtain phenotypic information in response to the surface changes of captured cancer cells. Without sophisticated instruments, we can know the phenotypic information on HepG2 cells in whole blood with a high level of sensitivity and rapid naked-eye tracking of on-cell phenotype changes of HepG2 cells undergoing epithelial–mesenchymal transition.

Extensive attention has been recently focused on designing signal adjustable biosensors. However, there are limited approaches available in this field. In this work, to visually track lysosomes with high contrast, we used the i-motif structure as a pH-responsive unit and proposed a novel strategy to regulate the fluorescence resonance energy transfer (FRET) response of the pH sensor. By simply splitting the i-motif into two parts and modulating the split parameters, we can tune the pH transition midpoint (pHt) from 5.71 to 6.81 and the signal-to-noise ratio (S/N) from 1.94 to 18.11. To facilitate the lysosome tracking, we combined the i-motif split design with tetrahedral DNA (Td). The obtained pH nanosensor (pH-Td) displays appropriate pHt(6.12) to trace lysosomes with high S/N (10.3). Benefited from the improved stability, the superior cell uptake and lysosomal location of pH-Td, the visualization of the distribution of lysosomes, the lysosome–mitochondria interaction, and the pH changes of lysosomes in response to different stimuli were successfully achieved in NIH 3T3 cells. We believe that the design concept of controlling the split sequence distance will provide a novel insight into the design of i-motif-based nanosensors and even inspire the construction of smart DNA nanodevices for sensing, disease diagnosis, and controllable drug delivery.

Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC50= 3.3 μM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50of 0.3 μM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.

Fingerprint formed through lifted papillary ridges is considered the best reference for personal identification. However, the currently available latent fingerprint (LFP) images often suffer from poor resolution, have a low degree of information, and require multifarious steps for identification. Herein, an individual Cloud-based fingerprint operation platform has been designed and fabricated to achieve high-definition LFPs analysis by using CsPbBr3perovskite nanocrystals (NCs) as eikonogen. Moreover, since CsPbBr3NCs have a special response to some fingerprint-associated amino acids, the proposed platform can be further used to detect metabolites on LFPs. Consequently, in virtue of Cloud computing and artificial intelligence (AI), this study has demonstrated a champion platform to realize the whole LFP identification analysis. In a double-blind simulative crime game, the enhanced LFP images can be easily obtained and used to lock the suspect accurately within one second on a smartphone, which can help investigators track the criminal clue and handle cases efficiently.

Glioblastoma (GBM) is one of the most fatal tumors in the brain, and its early diagnosis remains technically challenging due to the complex repertoires of oncogenic alterations and blood-brain barrier (BBB). GBM-derived specific exosomes can cross the BBB and circulate in body fluids, so they can be noninvasive biomarkers for the early diagnosis of GBM. Herein, we propose a sensitive and label-free electrochemical biosensor designed by using Zr-based metal–organic frameworks (Zr-MOFs) for the detection of GBM-derived exosomes with practical application. In the design, a peptide ligand can specifically bind with human epidermal growth factor receptor (EGFR) and EGFR variant (v) III mutation (EGFRvIII), which are overexpressed on the GBM-derived exosomes. Meanwhile, Zr-MOFs encapsulated with methylene blue can absorb on the surface of the exosomes due to the interaction between Zr4+and the intrinsic phosphate groups outside of exosomes. Consequently, the concentration of exosomes can be directly quantified by monitoring the electroactive molecules inside MOFs, ranging from 9.5 × 103to 1.9 × 107particles/μL with the detection of limit of 7.83 × 103particles/μL. Furthermore, this proposed biosensor can distinguish GBM patients from healthy groups, demonstrating the great prospect for early clinical diagnosis.

Mitochondria are crucial in the process of oxidative metabolism and apoptosis. Their morphology is greatly associated with the development of certain diseases. For specific and long-term imaging of mitochondrial morphology, we synthesized a new mitochondria-targeted near-infrared (NIR) fluorescent probe (TPE–Xan–In) by incorporating TPE with a NIR merocyanine skeleton (Xan–In). TPE–Xan–In displayed both absorption (660 nm) and emission peaks (743 nm) in the NIR region. Moreover, it showed aggregation-induced emission properties at neutral pH and specifically illuminated mitochondria with good biocompatibility, superior photostability, and high tolerance to mitochondrial membrane potential changes. With a pH-responsive unit, hydroxyl xanthene (Xan), the probe exhibited a pH-sensitive fluorescence emission in the range of pH 4.0–7.0, which indicated its potential in long-term tracking of pH and morphology changes of mitochondria in the biomedical research studies.

Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTBantigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs). By flow cytometry, we then dissected CD4+ and CD8+ T lymphocytes secreting intracellular cytokines of IFN-γ and TNF-α to assess the local immune response of TB patients with pulmonary cavities compared with those having other radiological infiltrates. As expected, after 16 h of ex vivo activation using both ESAT-6 and CFP-10, the proportions of CD4+IFN-γ, CD4+TNF-α, CD8+TNF-α, and CD8+IFN-γ cells were all markedly increased in 46 patients with TB when compared with 23 household contacts. However, the IFN-γ and TNF-α responses of both CD4+ and CD8+ T lymphocytes were found to be relatively lower in 18 patients who had pulmonary cavities when compared with 28 patients who had radiological infiltrates. Moreover, patients with cavities had higher absolute numbers of neutrophils than patients with infiltrates. Further analysis indicated an inverse correlation between neutrophil counts and the proportions of IFN-γ-secreting T cells. MTB-specific lymphocyte responses are impaired in TB patients with pulmonary cavities that are likely to play an important role in the pathogenesis of cavitary TB.

Immune checkpoint inhibitors have transformed the management of advanced cancers, but biomarkers for the prediction of therapeutic responses have not been fully uncovered. Here, we provide a step-by-step approach for the identification of novel biomarkers from public transcriptomic datasets. We comprehensively summarize the available transcriptomic datasets containing immunotherapy information and describe the necessary procedures to evaluate the effectiveness of a novel immunotherapy biomarker, which may accelerate the identification of novel immunotherapy biomarkers.

Peptidylarginine deiminase 4 (PAD4) is the only isoform of PADs located within the cell nucleus, which has been known to be related to several human diseases. In this work, we have proposed an electrochemical method for the assay of endogenous PAD4 activities as well as the studies of PAD4 inhibitors by making use of the supramolecular chemistry-assisted signal labeling. Specifically, peptide probes P1 and P2, which separately contain cysteine residues and tripeptides FGG (Phe-Gly-Gly), can be self-assembled onto the surface of the gold electrode and silver nanoparticles, respectively. In the meantime, the peptide probes can be connected together through cucurbit[8]uril-mediated host–guest interaction. Nevertheless, after trypsin-catalyzed digestion, FGG at the N-terminal of P1 will be removed from the electrode surface, thereby inhibiting the connection of P1 and P2. Since PAD4 catalyzes the citrullination of arginine residue within P1, trypsin-catalyzed digestion of P1 can be prohibited by the addition of PAD4. Consequently, an obvious change of the electrochemical response can be obtained from the silver nanoparticles (AgNPs) immobilized on the electrode surface. Experimental results have shown that our method can display an improved sensitivity and specificity for both PAD4 assay and inhibitor screening, which may effectively trace endogenous PAD4 and the inhibitors in the cancer cells. Therefore, our method may have great potential for the diagnosis and treatment of PAD4-related diseases in the future.

Low-temperature photothermal therapy (PTT) has the advantage of causing less damage to normal tissues and has attracted great attention in recent years. However, the efficacy of low-temperature PTT is restricted by the overexpression of heat shock proteins (HSPs), specifically HSP70 and HSP90. Inhibiting the function of these HSPs is a major strategy used in the development of new cancer therapies. Herein, we designed four T780T-containing thermosensitive nanoparticles to interrupt the energy supply for HSP expression using their TPP-based mitochondrial targeting action. The reversal behavior of the nanoparticles on the gambogic acid (GA)-induced compensatory increase of HSP70 was investigated in vitroby Western blot and in vivoby immunohistochemistry. The in vivoanticancer efficacy of the low-temperature PTT based on these thermosensitive nanoparticles was also systematically examined. The design proposes for the first time to utilize and elucidate the mechanism of the mitochondrial targeting of T780T-containing NPs in synergy with the HSP90 inhibition of GA to achieve an effective low-temperature PTT. This work not only provides a novel pathway for the dual inhibition of HSP70 and HSP90 but also opens up a new approach for low-temperature PTT of tumors.

Pulmonary cavitation is the classic hallmark of pulmonary tuberculosis (PTB) and is the site of very high mycobacterial burden associated with antimycobacterial drug resistance and treatment failure. The objective of this study was to investigate the relationship between re-treatment PTB and initial pulmonary cavitation coordinated with other clinical factors. We conducted a case–control study of 291 newly diagnosed cases of pulmonary TB in The Infectious Hospital of Wuxi from Dec 2009 to Dec 2011 with complete follow-up information until December 31st of 2014. 68 patients were followed-up with PTB re-treatment; the rest of the PTB patients (n= 223) had completed anti-TB treatment, and cured without re-treatment were selected as controls. The univariate analysis [hazard ratio (HR) 1.885, 95 % CI 1.170–3.035, P= 0.009] and the multivariable analysis (HR 2.242, 95 % CI 1.294–3.882, P= 0.004) demonstrated that the initial pulmonary cavitation was a prognostic predictor for TB re-treatment. Additionally, the re-treatment rates in PTB patients with cavitation and no-cavitation were 27.1 and 15.5 %, respectively, with significant difference (log-rank test; P= 0.010). Other factors, age of ≥60 and history of smoking, were also prognostic variables. Initial pulmonary cavitation of chest X-ray was a significant predictor for PTB re-treatment

In this study, a specific antibody against sirolimus was produced by its well synthesized immunogen and a competitive chemiluminescence immunoassay (CLIA) was established. The sirolimus molecule was modified with succinic anhydride (hapten 1) and carboxymethoxylamine (hapten 2). Hapten 1 was conjugated with bovine serum albumin to serve as the immunogen whilst hapten 2 was conjugated with ovalbumin for the coating antigen. A polyclonal antibody was prepared by immunizing rabbits with the purified immunogen. A CLIA method was established using the antibody for the analysis of sirolimus in phosphate-buffered saline and plasma. The limits of detection of the method in the two samples could reach 0.20 and 0.25 ng mL−1, respectively. Furthermore, this immunoassay was successfully applied to the pharmacokinetic study of sirolimus and the calculation of its pharmacokinetic parameters. The results suggest that this immunoassay has significant potential to be developed as a kit which can provide a sensitive, specific and inexpensive approach to therapeutic drug monitoring of sirolimus.

•Breast cancer is the main cause of cancer-related deaths in women.•Microproteins, comprising about 100 amino acids, have been demonstrated to play important roles in biology and disease.•TRPC5OS is encoded by short transient receptor potential channel 5 opposite strand as a microprotein of 111 amino acids, and predicted to correlate with tumor metabolic reprogramming.•Here we aim to elucidate the function of TRPC5OS in aberrant metabolism mediated tumorigenesis.•Our study demonstrated that TRPC5OS promotes breast tumorigenesis by ENO1/PI3K/Akt-mediated metabolic reprogramming.•TRPC5OS might be an independent prognostic marker and potential therapeutic target for breast cancer patients.

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent.

For routine monitoring of the pharmacokinetic behavior of anticancer drug methotrexate (MTX), polyclonal antibodies for MTX were originally produced, and a sensitive chemiluminescence immunoassay (CLIA) was developed for the determination of plasma MTX. Three kinds of coupling reagents (EDC, CDI and isobutyl chloroformate) were utilized to synthesize MTX immunogens. The coupling ratio, titer and sensitivity of polyclonal antibodies for each immunogen were evaluated. Consequently, MTX–EDC–cBSA was found to be the optimal immunogen since it showed the highest coupling ratio and yielded antibodies with the highest sensitivity. Under optimal conditions, the developed CLIA showed a limit of detection (LOD) of 4.3 ng mL−1in buffer and 9.1 ng mL−1in plasma with acceptable coefficients of variations (<14.9%). The method exhibited no cross-reaction with the MTX metabolite (7-OH MTX) and structural analogs. When applied in a pharmacokinetic study, the CLIA results were statistically consistent with the HPLC method in measuring key pharmacokinetic parameters (t1/2, Cmax, AUC0–12and MRT0–12). In conclusion, the CLIA method showed advantages of simple sample preparation, low cost, high sensitivity and good reproducibility. These properties make it a potential tool in the rapid detection of MTX for therapeutic drug monitoring (TDM).

Multidrug resistance(MDR) is a main factor to make the failure of chemotherapy. It is closely related to the over-expression of P-glycoprotein(P-gp), multidrug resistance protein(MRP) and breast cancer resistance protein( BCRP). Herein we reported a novel method to characterize MDR, taking advantage of the electrochemical property of chemotherapeutic drugs. Meanwhile, the definition of accumulation phase and retention phase has been improved. Furthermore, with specific modulators introduced to inhibit the relevant efflux pumps, the exact protein that mainly works in the cells employed in this study can be identified.