Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization.

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.

Hydrogel-Based Biosensors for Bacterial Infections.

Hydrogels are known to have the advantages such as good biodegradability, biocompatibility, and easy functionalization, making them ideal candidates for biosensors. Hydrogel-based biosensors that respond to bacteria-induced microenvironmental changes such as pH, enzymes, antigens, etc., or directly interact with bacterial surface receptors, can be applied for early diagnosis of bacterial infections, providing information for timely treatment while avoiding antibiotic abuse. Furthermore, hydrogel biosensors capable of both bacteria diagnosis and treatment will greatly facilitate the development of point-of-care monitoring of bacterial infections. In this review, the recent advancement of hydrogel-based biosensors for bacterial infection is summarized and discussed. First, the biosensors based on pH-sensitive hydrogels, bacterial-specific secretions-sensitive hydrogels, and hydrogels directly in contact with bacterial surfaces are presented. Next, hydrogel biosensors capable of detecting bacterial infection in the early stage followed by immediate on-demand treatment are discussed. Finally, the challenges and future development of hydrogel biosensors for bacterial infections are proposed.

Assessing the necessity of screening ≤5 Mb segmental aneuploidy in routine PGT for aneuploidies.

RESEARCH QUESTION: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb? DESIGN: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed. RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage. CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.

Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification.

The extracellular matrix (ECM) is mechanically inhomogeneous due to the presence of a wide spectrum of biomacromolecules and hierarchically assembled structures at the nanoscale. Mechanical inhomogeneity can be even more pronounced under pathological conditions due to injury, fibrogenesis, or tumorigenesis. Although considerable progress has been devoted to engineering synthetic hydrogels to mimic the ECM, the effect of the mechanical inhomogeneity of hydrogels has been widely overlooked. Here, we develop a method based on host-guest chemistry to control the homogeneity of maleimide-thiol cross-linked poly(ethylene glycol) hydrogels. We show that mechanical homogeneity plays an important role in controlling the differentiation or stemness maintenance of human embryonic stem cells. Inhomogeneous hydrogels disrupt actin assembly and lead to reduced YAP activation levels, while homogeneous hydrogels promote mechanotransduction. Thus, the method we developed to minimize the mechanical inhomogeneity of hydrogels may have broad applications in cell culture and tissue engineering.

Toxicity of the sunscreen UV filter benzophenone-3 (OBZ) to the microalga Selenastrum capricornutum: An insight into OBZ's damage to photosynthesis and respiration.

Oxybenzone (OBZ; benzophenone-3, CAS# 131-57-7), as a new pollutant and ultraviolet absorbent, shows a significant threat to the survival of phytoplankton. This study aims to explore the acute toxic effects of OBZ on the growth of the microalga Selenastrum capricornutum, as well as the mechanisms for its damage to the primary metabolic pathways of photosynthesis and respiration. The results demonstrated that the concentrations for 50 % of maximal effect (EC50) of OBZ for S. capricornutum were 9.07 mg L-1 and 8.54 mg L-1 at 72 h and 96 h, respectively. A dosage of 4.56 mg L-1 OBZ significantly lowered the photosynthetic oxygen evolution rate of S. capricornutum in both light and dark conditions for a duration of 2 h, while it had no effect on the respiratory oxygen consumption rate under darkness. OBZ caused a significant decline in the efficiency of photosynthetic electron transport due to its damage to photosystem II (PSII), thereby decreasing the photosynthetic oxygen evolution rate. Over-accumulated H2O2 was produced under light due to the damage caused by OBZ to the donor and acceptor sides of PSII, resulting in increased peroxidation of cytomembranes and inhibition of algal respiration. OBZ's damage to photosynthesis and respiration will hinder the conversion and reuse of energy in algal cells, which is an important reason that OBZ has toxic effects on S. capricornutum. The present study indicated that OBZ has an acute toxic effect on the microalga S. capricornutum. In the two most important primary metabolic pathways in algae, photosynthesis is more sensitive to the toxicity of OBZ than respiration, especially in the dark.

NIR-II Perylene Monoimide-Based Photothermal Agent with Strengthened Donor-Acceptor Conjugation for Deep Orthotopic Glioblastoma Phototheranostics.

Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.

Supramolecular Photonic Hydrogel for High-Sensitivity Alkaline Phosphatase Detection via Synergistic Driving Force.

Structurally-colored photonic hydrogels which are fabricated by introducing hydrogels into thin films or photonic crystal structures are promising candidates for biosensing. Generally, the design of photonic hydrogel biosensors is based on the sensor-analyte interactions induced charge variation within the hydrogel matrix, or chemically grafting binding sites onto the polymer chains, to achieve significant volume change and color variation of the photonic hydrogel. However, relatively low anti-interference capability or complicated synthesis hinder the facile and low-cost fabrication of high-performance photonic hydrogel biosensors. Here, a facilely prepared supramolecular photonic hydrogel biosensor is developed for high-sensitivity detection of alkaline phosphatase (ALP), which is an extensively considered clinical biomarker for a variety of diseases. Responding to ALP results in the broken supramolecular crosslinking and thus increased lattice distancing of the photonic hydrogel driven by synergistic repulsive force between nanoparticles embedded in photonic crystal structure and osmotic swelling pressure. The biosensor shows sensitivity of 7.3 nm spectral shift per mU mL-1 ALP, with detection limit of 0.52 mU mL-1 . High-accuracy colorimetric detection can be realized via a smartphone, promoting point-of-care sensing and timely diagnosis of related pathological conditions.

Immunomodulatory and antiviral effects of Lycium barbarum glycopeptide on influenza a virus infection.

Influenza is caused by a respiratory virus and has a major global impact on human health. Influenza A viruses in particular are highly pathogenic to humans and have caused multiple pandemics. An important consequence of infection is viral pneumonia, and with serious complications of excessive inflammation and tissue damage. Therefore, simultaneously reducing direct damage caused by virus infection and relieving indirect damage caused by excessive inflammation would be an effective treatment strategy. Lycium barbarum glycopeptide (LbGp) is a mixture of five highly branched polysaccharide-protein conjuncts (LbGp1-5) isolated from Lycium barbarum fruit. LbGp has pro-immune activity that is 1-2 orders of magnitude stronger than that of other plant polysaccharides. However, there are few reports on the immunomodulatory and antiviral activities of LbGp. In this study, we evaluated the antiviral and immunomodulatory effects of LbGp in vivo and in vitro and investigated its therapeutic effect on H1N1-induced viral pneumonia and mechanisms of action. In vitro, cytokine secretion, NF-κB p65 nuclear translocation, and CD86 mRNA expression in LPS-stimulated RAW264.7 cells were constrained by LbGp treatment. In A549 cells, LbGp can inhibit H1N1 infection by blocking virus attachment and entry action. In vivo experiments confirmed that administration of LbGp can effectively increase the survival rate, body weight and decrease the lung index of mice infected with H1N1. Compared to the model group, pulmonary histopathologic symptoms in lung sections of mice treated with LbGp were obviously alleviated. Further investigation revealed that the mechanism of LbGp in the treatment of H1N1-induced viral pneumonia includes reducing the viral load in lung, regulating the phenotype of pulmonary macrophages, and inhibiting excessive inflammation. In conclusion, LbGp exhibits potential curative effects against H1N1-induced viral pneumonia in mice, and these effects are associated with its good immuno-regulatory and antiviral activities.

Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups.

Inflammation is the initial biological reaction of the immune system to various stimuli such as infection, injury, or irritation. Extensive research has demonstrated that a growing array of diseases are triggered by inflammatory mechanisms. Currently, anti-inflammatory drugs are widely utilized in clinical practice due to their therapeutic advantages; however, the potential side effects cannot be ignored by us. In our work, a series of amide compounds with chromones as the parent nucleus were designed and synthesized using the principle of colligated drug design. The results of the biological evaluation indicated that four compounds exhibited lower EC50 values compared to the positive drug ibuprofen. Notably, compound 5-9 showed optimal inhibitory activity (EC50 = 5.33 ± 0.57 µM) against the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells. Structure-activity relationships (SAR) showed that the presence of electron-withdrawing groups at positions 5 and 8, or electron-donating groups at positions 6 and 7 of the parent nucleus of the chromones can enhance the anti-inflammatory activity of the chromones. The molecular docking studies predicted the mode of interaction between the compounds and protein. Additionally, these studies have demonstrated that the amide bond is the key radical to the anti-inflammatory effect. Based on the summary of the aforementioned studies, it can be inferred that compound 5-9 exhibit potential as an anti-inflammatory drug that deserves further investigation.

Perception of risk of relapse among patients with first episode and recurrent schizophrenia: a descriptive phenomenological study.

BACKGROUND: Patients suffering from schizophrenia are at a higher risk of relapse. The perception of the risk of relapse in patients is critical for relapse prevention. In the field of psychiatry, the study of risk perception of relapse has been neglected. METHODS: We carried out a qualitative study using a descriptive phenomenological approach. Data were collected at two psychiatric hospitals in China. In total, 22 patients with schizophrenia were recruited through purposive sampling. Face to face semi-structured in-depth interviews were conducted. Interview recordings were transcribed by the research team, and transcripts were analysed by two independent coders with Colaizzi's descriptive analysis framework. The consolidated criteria for reporting qualitative research checklist were used for reporting. RESULTS: The data of first-episode patients yielded three themes: (i) lack of knowledge about disease recognition and medical treatment; (ii) overoptimistic estimation of the risk of relapse; (iii) perceived importance of treatment. For first-relapse patients : (i) initial awareness of relapse warning signs; (ii) lack of systematic and accurate assessment of disease information; (iii) the perception that drug withdrawal is related to relapse. Patients with multiple relapses: (i) susceptibility to relapse: confusion and powerlessness; (ii) the severity of relapse: suicidal thoughts and behavior; (iii) effects of perceived benefits and barriers of medication behaviour. CONCLUSIONS: In schizophrenic patients with first-episode, first-relapse, and multiple relapses, there were dynamic changes in the perception of disease relapse risk and medication behaviour. Medical workers must improve risk awareness education. They should provide patients with scientific, accurate, and timely communication channels, and dynamically assess and manage the risk of relapse in various patients.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Unsupervised clustering analysis of comprehensive health status and its influencing factors on women of childbearing age: a cross-sectional study from a province in central China.

BACKGROUND: Most previous studies on women of childbearing age have focused on reproductive health and fertility intentions, and evidence regarding the comprehensive health status of women of childbearing age is limited. This study aimed to comprehensively examine the health status of women of childbearing age through a multi-method and multi-indicator evaluation, analyze the factors that influence their overall health, and provide sound recommendations for the improvement and promotion of healthy behaviors. METHODS: Data on women of childbearing age living in Shanxi Province were collected between September 2021 and January 2022 through online and offline surveys. The k-means algorithm was used to assess health-related patterns in women, and multivariate nonconditional logistic regression was used to assess the influencing factors of women's overall health. RESULTS: In total, 1,258 of 2,925 (43%) participants were classified as having a good health status in all five domains of the three health dimensions: quality of life, mental health, and illness. Multivariate logistic regression showed that education level, gynecological examination status, health status of family members, access to medical treatment, age, cooking preferences, diet, social support, hand washing habits, attitude toward breast cancer prevention, and awareness of reproductive health were significantly associated with different health patterns. CONCLUSIONS: The comprehensive health status of women of childbearing age in Shanxi Province is generally good; however, a large proportion of women with deficiencies in some dimensions remains. Since lifestyle greatly impacts women's health, health education on lifestyle and health-related issues should be strengthened.

Total saponins of panax ginseng via the CX3CL1/CX3CR1 axis attenuates neuroinflammation and exerted antidepressant-like effects in chronic unpredictable mild stress in rats.

Total saponins of Panax ginseng (TSPG) have antidepressant effects. However, the underlying antidepressant mechanism of TSPG remains not clear. This study aimed to predict the mechanism of TSPG by bioinformatics analysis and to verify it experimentally. Bioinformatics analysis showed that the antidepressant effects of TSPG may be related to inflammation, and CX3CL1/CX3CR1 may play a key mediating role. Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and TSPG (50 mg/kg/d, 100 mg/kg/d) was administered throughout the modeling period. It was found that TSPG improves depressive behavior and reduces neuropathic damage in the hippocampus in rats. Meanwhile, TSPG decreased mRNA and protein expression of pro-inflammatory cytokines and CX3CL1/CX3CR1 and inhibited P38 and JNK protein phosphorylation in the hippocampus. Rat astrocytes were employed to explore further the potential mechanism of TSPG in regulating CX3CL1/CX3CR1. The results showed that CX3CL1 small interfering RNA (siRNA-CX3CL1) and CX3CR1 inhibitor (JMS-17-2) had similar effects to TSPG, that is, reduced inflammatory response, reactive oxygen species (ROS), and phosphorylation of P38 and JNK proteins, while overexpression of CX3CL1 (pcDNA-CX3CL1) counteracted the above effects of TSPG. It is suggested that the antidepressant effect of TSPG may be achieved through inhibition of CX3CL1/CX3CR1.

LncRNA Miat knockdown protects against pirarubicin-induced cardiotoxicity by targeting miRNA-129-1-3p.

Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. The aim of this study was to investigate the protective effect and mechanism of knockdown of lncRNA Miat in THP-induced cardiotoxicity. The extent of damage to immortalized cardiomyocytes in mice was assessed by CCK8, TUNEL, ROS, Ca2+ , RT-qPCR, and Western blot. The relative levels of Miat in THP-treated cardiomyocytes (HL-1) were measured. The protective effect of Miat on THP-treated HL-1 was assessed. The binding relationship between lncRNA Miat and mmu-miRNA-129-1-3p was verified by a dual luciferase reporter gene assay. The protective role of Miat/miRNA-129-1-3p in THP-induced HL-1 was explored by performing a rescue assay. THP reduced cell viability, induced apoptosis, triggered oxidative stress and calcium overload. Expression of Miat in HL-1 was significantly elevated after THP treatment. Miat knockdown significantly alleviated the cardiotoxicity of THP. MiR-129-1-3p is a direct target of Miat. Knockdown of miR-129-1-3p reversed the protective effect of Miat knockdown on HL-1. Miat knockdown can alleviate THP-induced cardiomyocyte injury by regulating miR-129-1-3p.

MiR-494-3p aggravates pirarubicin-induced cardiomyocyte injury by regulating MDM4/p53 signaling pathway.

OBJECTIVE: Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. There is an urgent need to find drugs to alleviate the cardiotoxicity of THP. This study aimed to investigate the effect and mechanism of miR-494-3p on THP-induced cardiomyocytes. METHODS: THP induced immortalized mouse cardiomyocytes HL-1, silenced or overexpressed miR-494-3p. The effects of miR-494-3p on HL-1 contained in THP were investigated by CCK8, flow cytometry, ROS detection, JC-1 mitochondrial membrane potential detection, TUNEL cell apoptosis detection, RT-qPCR, and Western blot. RESULTS: miR-494-3p could reduce cell viability, increase oxidative damage, and promote cell apoptosis; at the same time, it inhibited the expression of MDM4, promoted the activation of p53, and promoted the expression of apoptosis-related proteins. MiR-494-3p inhibitors have the opposite effect. CONCLUSION: miR-494-3p can aggravate THP damage to HL-1, which may be achieved by downregulating MDM4 and promoting p53. miR-494-3p is one of the important miRNAs in THP-induced cardiotoxicity, which provides theoretical support for its possible use as a therapeutic target for THP-induced cardiovascular disease.

When biochar is involved in rhizosphere dissipation and plant absorption of pesticides: A meta-analysis.

Clarifying the influences of biochar input on the rhizosphere dissipation and plant absorption of pesticides is a crucial prerequisite for utilizing biochar in the restoration of pesticide-contaminated soils. Nevertheless, the application of biochar to pesticide-contaminated soils does not always achieve consistent results on the rhizosphere dissipation and plant absorption of pesticides. Under the new situation of vigorously promoting the application of biochar in soil management and carbon sequestration, a timely review is needed to further understand the key factors affecting biochar remediation of pesticide-contaminated soil. In this study, a meta-analysis was conducted utilizing variables from three dimensions of biochar, remediation treatment, and pesticide/plant type. The pesticide residues in soil and the pesticide uptake by plant were used as response variables. Biochar with high adsorption capacity can impede the dissipation of pesticides in soil and mitigate their absorption by plants. The specific surface area of biochar and the type of pesticide are critical factors that affect pesticide residues in soil and plant uptake, respectively. Applying biochar with high adsorption capacity, based on specific dosages and soil characteristics, is recommended for the remediation of continuously cultivated soil contaminated with pesticides. This article aims to provide a valuable reference and understanding for the application of biochar-based soil remediation technology and the treatment of pesticide pollution in soil.

Emotive Tonality of the "Youth-Old Age" Dichotomy in Russian and Chinese Media Discourses: The Stage of Psychosemantic Expertise.

The issue of attitude to age has the character of social stigma at different stages of human civilization, therefore, the identification of the general and particular in the assessments of the "youth-old age" dichotomy in different structural languages seems relevant. The results are based on the materials of an in-depth interview among 510 respondents belonging to different age groups: young, middle, and elderly; and 1257 respondents' responses. The in-depth interview covered 128 characteristics of interpersonal interaction. This made it possible to compile descriptor tables. The 54 characteristics identified were 27 bipolar scales. The objects of evaluation are characterized by 8 pole positions. A comparison was also made with data extracted from 368 articles in Russian and Chinese media. This work contributes to the understanding of the psycholinguistic processes of emotional perception of age in Russian and Chinese linguistic cultures.

Toward High Sensitivity: Perspective on Colorimetric Photonic Crystal Sensors.

The sensitivity of colorimetric photonic crystal (PC) sensors have been significantly improved with the advancement of deformable structural color materials, structures design, sensing signal analysis methods, and fabrication strategies. In this perspective, the strategies toward high-sensitivity colorimetric PC sensors are discussed, from the perspectives of molecular design, single sensor construction, and multisensor assembly, which include incorporation of flexible polymer chains, construction of strong sensor-analyte interactions, incorporation of more soft materials, construction of stimuli-angle/orientation relationship, design of colorimetric sensors in series, and assembly of colorimetric PC sensors in parallel. Based on these strategies, progress of high-sensitivity colorimetric PC sensors in recent years is summarized, in terms of mechano-sensors and chemo-/biosensors. Specifically, PC based optical-electrical dual-signal sensing devices are included. Finally, the future development and challenges of high-sensitivity colorimetric PC sensors are presented, in regards to deformable properties, optical properties, analysis methods, and fabrication strategies.

Tertiary lymphoid structures are associated with favorable survival outcomes in patients with endometrial cancer.

Immunotherapy has experienced remarkable growth recently. Tertiary lymphoid structures (TLSs) and B cells may play a key role in the immune response and have a survival benefit in some solid tumors, but there have been no reports about their role in endometrial cancer (EC). We investigated the clinicopathological and pathobiological characteristics of the tumor microenvironment (TME) in EC. Patients with EC at Kyoto University Hospital during 2006-2011 were retrospectively included. In 104 patients with EC who met study inclusion criteria, 81 (77.9%) had TLSs, which consisted of areas rich in CD20+ B cells, CD8+ T cells, CD4+ T cells, and CD38+ plasma cells. The absence of TLS was independently associated with tumor progression (HR, 0.154; 95% CI, 0.044-0.536; P = 0.003). Patients with TLSs that included CD23+ germinal centers had better PFS. All tumor infiltrating lymphocytes were counted in the intratumor site. The number of CD20+ B cells was significantly larger in patients with TLSs than in those without TLS (P < 0.001). CD20+ B cells numbers were positively correlated with other TLSs. The larger number of CD20+ B cell was associated with better PFS (P = 0.015). TLSs and B cell infiltration into tumors are associated with favorable survival outcomes in patients with EC. They may represent an active immune reaction of the TME in endometrial cancer.

Deep-Penetrating Triple-Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models.

Chemoradiotherapy (CRT) is the most accepted treatment for locally advanced pancreatic ductal adenocarcinoma (PDAC) and can significantly improve the R0 resection rate. However, there are few long-term survivors after CRT. Although some polymer nanoparticles have shown potential in alleviating the dose-limiting toxicity and assisting the chemotherapy of PDAC, there are few efficient nanosensitizers (NS) available for CRT of this malignancy, especially in the context of its hypoxic nature. Herein, based on the biological features of PDAC, a γ-glutamyl transpeptidase (GGT)/glutathione (GSH)/hypoxia triple-responsive prodrug NS to overcome the biological barrier and microenvironmental limitations confronted by CRT in PDAC is developed. Due to triple-responsiveness, deep tumor penetration, GSH/hypoxia-responsive drug release/activation, and hypoxia-induced chemoradio-sensitization can be simultaneously achieved with this NS. As a result, tumor shrinkage after CRT with this NS can be observed in both subcutaneous and orthotopic PDAC models, foreshadowing its potential in clinical neoadjuvant CRT.