Self-powered soft robot in the Mariana Trench.

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

Fluorine-18 labeling PEGylated 6-boronotryptophan for PET scanning of mice for assessing the pharmacokinetics for boron neutron capture therapy of brain tumors.

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies. Shorter PEG compound 6-boronotryptophanPEG200[18F] was obtained in 1.7 % radiochemical yield and the PET-derived radioradioactivity percentage in 18 % was taken up by U87 tumor at the limb of xenograft mouse. As high as tumor to normal uptake ratio in 170 (T/N) was obtained while an inferior radioactivity uptake of 3 % and T/N of 8 was observed in LN229 xenografted mouse.

Design, synthesis and evaluation of novel prostate-specific membrane antigen-targeted aryl [18F]fluorosulfate PET tracers.

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.

A Novel Homoconjugated Propellane Triimide: Synthesis, Structural Analyses, and Gas Separation.

Rigid three-dimensional (3D) polycyclic propellanes have garnered interest due to their unique conformational spaces, which display great potential use in selectivity, separation and as models to study through-space electronic interactions. Herein we report the synthesis of a novel rigid propellane, trinaphtho[3.3.3]propellane triimide, which comprises three imide groups embedded on a trinaphtho[3.3.3]propellane. This propellane triimide exhibits large bathochromic shift, amplified molar absorptivity, enhanced fluorescence, and lower reduction potential when compared to the subunits. Computational and experimental studies reveal that the effective through-space π-orbitals interacting (homoconjugation) occurs between the subunits. Single-crystal XRD analysis reveals that the propellane triimide has a highly quasi-D3h symmetric skeleton and readily crystallizes into different superstructures by changing alkyl chains at the imide positions. In particular, the porous 3D superstructure with S-shaped channels is promising for taking up ethane (C2H6) with very good selectivity over ethylene (C2H4), which can purify C2H4 from C2H6/C2H4 in a single separation step. This work showcases a new class of rare 3D polycyclic propellane with intriguing electronic and supramolecular properties.

Monitoring Bipolar Electrochemistry and Hydrogen Evolution Reaction of a Single Gold Microparticle under Sub-Micropipette Confinement.

Herein, an approach to track the process of autorepeating bipolar reactions and hydrogen evolution reaction (HER) on a micro gold bipolar electrode (BPE) is established. Once blocking the channel of the sub-micropipette tip, the formed gold microparticle is polarized into the wireless BPE, which induces the dissolution of the gold at the anode and the HER at the cathode. The current response shows a periodic behavior with three regions: the bubble generation region (I), the bubble rupture/generation region (II), and the channel opening region (III). After a stable low baseline current of region I, a series of positive spike signals caused by single H2 nanobubbles rupture/generation are recorded standing for the beginning of region II. Meanwhile, the dissolution of the gold blocking at the orifice will create a new channel, increasing the baseline current for region III, where the synthesis of gold occurs again, resulting in another periodic response. Finite element simulations are applied to unveil the mechanism thermodynamically. In addition, the integral charge of the H2 nanobubbles in region II corresponds to the consumption of the anode gold. It simultaneously monitors autorepeating bipolar reactions of a single gold microparticle and HER of a single H2 nanobubble electrochemically, which reveals an insightful physicochemical mechanism in nanoscale confinement and makes the glass nanopore an ideal candidate to further reveal the heterogeneity of catalytic capability at the single particle level.

Effects of the Implementation of Intelligent Technology for Hand Hygiene in Hospitals: Systematic Review and Meta-analysis.

BACKGROUND: The World Health Organization recommends regular hand hygiene monitoring and feedback to improve hand hygiene behaviors and health care-associated infection rates. Intelligent technologies for hand hygiene are increasingly being developed as alternative or supplemental monitoring approaches. However, there is insufficient evidence regarding the effect of this type of intervention, with conflicting results in the literature. OBJECTIVE: We conduct a systematic review and meta-analysis to evaluate the effects of using intelligent technology for hand hygiene in hospitals. METHODS: We searched 7 databases from inception to December 31, 2022. Two reviewers independently and blindly selected studies, extracted data, and assessed the risk of bias. A meta-analysis was performed using the RevMan 5.3 and STATA 15.1 software. Sensitivity and subgroup analyses were also conducted. Overall certainty of evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation approach. The systematic review protocol was registered. RESULTS: The 36 studies comprised 2 randomized controlled trials and 34 quasi-experimental studies. The included intelligent technologies involved 5 functions: performance reminders，electronic counting and remote monitoring，data processing，feedback，and education. Compared with usual care, the intelligent technology intervention for hand hygiene improved health care workers' hand hygiene compliance (risk ratio 1.56, 95% CI 1.47-1.66; P<.001), reduced health care-associated infection rates (risk ratio 0.25, 95% CI 0.19-0.33; P<.001), and was not associated with multidrug-resistant organism detection rates (risk ratio 0.53, 95% CI 0.27-1.04; P=.07). Three covariates, including publication year, study design, and intervention, were not factors of hand hygiene compliance or hospital-acquired infection rates analyzed by meta-regression. Sensitivity analysis showed stable results except for the pooled outcome of multidrug-resistant organism detection rates. The caliber of 3 pieces of evidence suggested a dearth of high-caliber research. CONCLUSIONS: Intelligent technologies for hand hygiene play an integral role in hospital. However, low quality of evidence and important heterogeneity were observed. Larger clinical trials are required to evaluate the impact of intelligent technology on multidrug-resistant organism detection rates and other clinical outcomes.

Spatiotemporal distribution and probabilistic health risk assessment of arsenic in drinking water and wheat in Northwest China.

Drinking water arsenic poisoning has been a health concern, however the importance of dietary arsenic exposure to health also needs to be taken into account. The aim of this study was to conduct a comprehensive health risk assessment of arsenic-contaminated substances in drinking water and wheat-based food intake in the Guanzhong Plain, China. 87 samples of wheat and 150 samples of water were randomly selected from the research region and examined. The level of arsenic in 89.33% of the water samples in the region exceeded the limit for drinking water (10 µg/L), with an average concentration of 29.98 µg/L. The arsenic in 2.13% of the wheat samples exceeded the food limit (0.5 mg/kg) with an average concentration of 0.24 mg/kg. Under the situation of different exposure pathways, two scenarios of deterministic and probabilistic health risk assessments were compared and analyzed. By contrast, the probabilistic health risk assessment can ensure a certain degree of confidence in the assessment results. The findings of this study indicated that the total cancer risk value faced by the population aged 3-79 years, except for those aged 4-6 years, was 1.03E-4-1.21E-3, which exceeded the 10E-6-10E-4 range of thresholds usually used by USEPA as guidance recommendations for determination. And the non-cancer risk experienced by the population aged 6 months to 79 years was higher than the acceptable threshold (1), with children aged 9 months to 1 year having the highest total non-cancer risk of 7.25. The potential health risks of the exposed population were mainly due to the drinking water route, and consumption of arsenic-containing wheat increased both carcinogenic and non-carcinogenic risks. Finally, the sensitivity analysis revealed that the assessment findings were most significantly influenced by exposure time. The amount of intake was the second influencing factor in the health risk assessment from drinking water and dietary intakes of arsenic, and arsenic concentration was the second influencing factor in the health risk assessment due to dermal exposure to arsenic. The findings of this study can aid in understanding the negative health consequences of arsenic pollution to local residents and in adopting focused remediation strategies to alleviate environmental concerns.

Critical care nurses' experiences of physical restraint in intensive care units: A qualitative systematic review and meta-synthesis.

INTRODUCTION: Physical restraint is widely used in intensive care units. Critical care nurses are the primary decision makers and practitioners of physical restraint. However, little is known about the qualitative evidence of their experience of physical restraint. AIMS: To aggregate, synthesise and interpret the qualitative evidence of studies that explored critical care nurses' experiences of physical restraint in intensive care units. METHODS: A qualitative systematic review and meta-synthesis was conducted following Joanna Briggs Institute methodology and reported following the ENTREQ statement. Qualitative studies published in the English and Chinese were systematically searched in eight databases. PubMed, Web of Science, CINAHL, EMBASE, PsycINFO, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature Database from inception to November 2021. Two reviewers independently assessed the study eligibility and performed the data extraction and the quality appraisal. A meta-aggregative approach was used to synthesise findings. The review protocol was registered prospectively with PROSPERO (CRD42021278671). RESULTS: Thirteen studies were included. A total of 48 intact and definite codes were extracted and classified into ten sub-categories. Four themes were finally identified: intention, alternatives, determinants, and reflection. CONCLUSION: The intention of critical care nurses to use physical restraint is primarily driven by patient safety. Nurses will consider alternatives; however, many determinants urge nurses to implement physical restraint. Nurses prefer to sacrifice patients' comfort to ensure their safety. When nurses reflect on what they have done, some experience moral distress, but most rationalise their decision making. Further studies should explore the safety of alternatives, reduce the use of physical restraint, and pay more attention to nurses' moral distress through these insights. RELEVANCE TO CLINICAL PRACTICE: Developing alternatives, providing relevant training for nurses, physicians, patients, and families to facilitate a restraint-free culture, and developing high-quality guidelines and regulations are essential strategies to reduce the use of physical restraint in ICUs.

All-optical microwave waveform transformation based on photonic temporal processors.

An all-photonic approach of microwave waveforms generation and transformation is proposed and experimentally demonstrated. From the perspective of envelope function operation in time domain, an initial triangular waveform is transformed into square waveform and sawtooth (or reversed-sawtooth) waveform via two types of differentiators, respectively. In addition, by using a SOA as a multiplier, both bright and dark parabolic pulses are achieved, which are further transformed into sawtooth (or reversed-sawtooth) waveform by taking the first derivative operation. The feasibility of the system is verified by theoretical analysis and simulation. In experiment, all of the expected results are successfully demonstrated and agree with the theoretical analysis well. This scheme provides a novel access to implement all-optical microwave waveforms generation, transformation, signal processing and computing.

Development and implementation of a novel decision support tool on physical restraint use in critically ill adult patients.

AIM: To investigate whether a novel decision support tool would effectively minimize physical restraint use in critically ill adult patients. DESIGN: A nonequivalent quasi-experimental design combined with a descriptive qualitative approach was used. METHODS: A Restraint Decision Tree was developed based on a qualitative study that explored the barriers to employ the Restraint Decision Wheel. During the quasi-experimental study, patients admitted to the unit between October 2017 and March 2018 were enrolled as the control group receiving the Restraint Decision Wheel (n = 528), whereas patients between April 2018 and September 2018 were enrolled as the intervention group receiving the Restraint Decision Tree (n = 564). The physical restraint rate, accidental catheter removal rate and nurses' satisfaction were compared. RESULTS: The Restraint Decision Tree significantly decreased physical restraint use. No significant difference in the rate of accidental catheter removal was found. Nurses reported increased satisfaction with the restraint decision-making. CONCLUSIONS: The Restraint Decision Tree could minimize physical restraint use. Physicians' involvement in the restraint decision-making and nurses' competence in delirium assessment may be essential for successful implementation of the Restraint Decision Tree.

Single-cell transcriptome analysis revealed the heterogeneity and microenvironment of gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. In this study, we performed single-cell RNA sequencing (RNA-seq) on intra- and peri-tumor tissues from GIST patients with the aim of discovering the heterogeneity of tumor cells in GIST and their interactions with other cells. We found four predominating cell types in GIST tumor tissue, including T cells, macrophages, tumor cells, and NK cells. Tumor cells could be clustered into two groups: one was highly proliferating and associated with high risk of metastasis, the other seemed "resting" and associated with low risk. Their clinical relevance and prognostic values were confirmed by RNA-seq of 65 GIST samples. T cells were the largest cell type in our single-cell data. Two groups of CD8+ effector memory (EM) cells were in the highest clonal expansion and performed the highest cytotoxicity but were also the most exhausted among all T cells. A group of macrophages were found polarized to possess both M1 and M2 signatures, and increased along with tumor progression. Cell-to-cell interaction analysis revealed that adipose endothelial cells had high interactions with tumor cells to facilitate their progression. Macrophages were at the center of the tumor microenvironment, recruiting immune cells to the tumor site and having most interactions with both tumor and nontumor cells. In conclusion, we obtained an overview of the GIST microenvironment and revealed the heterogeneity of each cell type and their relevance to risk classifications, which provided a novel theoretical basis for learning and curing GISTs.

Changes in Alternative Splicing in Response to Domestication and Polyploidization in Wheat.

Alternative splicing (AS) occurs extensively in eukaryotes as an important mechanism for regulating transcriptome complexity and proteome diversity, but variation in the AS landscape in response to domestication and polyploidization in crops is unclear. Hexaploid wheat (AABBDD, Triticum aestivum) has undergone two separate allopolyploidization events, providing an ideal model for studying AS changes during domestication and polyploidization events. In this study, we performed high-throughput transcriptome sequencing of roots and leaves from wheat species with varied ploidies, including wild diploids (AbAb, Triticum boeoticum) and tetraploids (AABB, Triticum dicoccoides), domesticated diploids (AmAm, Triticum monococcum) and tetraploids (AABB, Triticum dicoccum), hexaploid wheat (AABBDD, T aestivum), as well as newly synthesized hexaploids together with their parents. Approximately 22.1% of genes exhibited AS, with the major AS type being intron retention. The number of AS events decreased after domestication in both diploids and tetraploids. Moreover, the frequency of AS occurrence tended to decrease after polyploidization, consistent with the functional sharing model that proposes AS and duplicated genes are complementary in regulating transcriptome plasticity in polyploid crops. In addition, the subgenomes exhibited biased AS responses to polyploidization, and ∼87.1% of homeologs showed AS partitioning in hexaploid wheat. Interestingly, substitution of the D-subgenome modified 42.8% of AS patterns of the A- and B-subgenomes, indicating subgenome interplay reprograms AS profiles at a genome-wide level, although the causal-consequence relationship requires further study. Conclusively, our study shows that AS variation occurs extensively after polyploidization and domestication in wheat species.

A green rust-coated expanded perlite particle electrode-based adsorption coupling with the three-dimensional electrokinetics that enhances hexavalent chromium removal.

A green rust-coated expanded perlite (GR-coated Exp-p) microelectrode was synthesized and incorporated into a column-mode three-dimensional electrokinetic (3D-EK) platform to effectively pursue a continuous Cr(VI) removal from the aqueous solution. Brucite-like layers of GR were decorated onto the Exp-p material. The molar ratio of Fe(II) to Fe(III) played a most vital role among the three synthesis factors in influencing the performance of the particle electrode. For the equilibrium adsorption experiments, the target maximum adsorption capacity of 122 mg/g was predicted by a target optimizer and desirability function at the conditions following the pH of 4.7, the initial concentration of 172.4 mg/L, the dosage of 0.28 g/L, and the temperature of 28.96 °C, respectively. SO42-, Cl-, and NO3- fiercely competed with Cr(VI) anions in the acidic conditions for the locally positive sites. A low concentration and a slow flow were favored in the column-mode 3D-EK platform. The pseudo-first-order and Langmuir models were suitable for describing the kinetics and isotherms of the adsorption process, respectively. Cr(VI) anions were electrostatically attracted to the silanol groups and GR surface of the adsorbent, subsequently reduced in both heterogeneity and homogeneity, and finally immobilized by coordinating with silanediol groups and silanetriol groups.

[Correlation of B-type Natriuretic Peptide Level with Hemodynamic Parameters and Inflammatory Cytokines in Patients with Gram-negative Sepsis].

Objective To study the correlation of B-type natriuretic peptide(BNP)level with hemodynamic parameters and inflammatory cytokines in patients with Gram-negative sepsis,and further determine the main factors for the significant increase of BNP level. Methods The prospective study method was applied,and septic patients infected with Gram-negative bacteria from May 2017 to October 2019 were enrolled.The patients were divided into the BNP<2400 ng/L group and the BNP≥2400 ng/L group by taking the average value of BNP as the dividing point.The independent predictors of BNP≥2400 ng/L were analyzed by Logistic regression.Pearson correlation analysis was used to analyze the correlation between BNP and various indicators. Results A total of 106 patients with Gram-negative sepsis were included,among which 60 cases present with higher serum BNP levels than the average of(2398.45 ± 421.45)ng/L.Thus BNP≥2400 ng/L was considered as a significantly increased BNP level.Multiple logistic regression analysis showed that cardiac index(CI)[odds ratio (OR)=0.428,95% confidence interval (95%CI)=0.743-0.965,P=0.011],left ventricular ejection fraction(LVEF) (OR=0.394,95%CI=0.182-0.549,P=0.013),lactic acid (OR=1.983,95%CI=1.264-3.420,P=0.023),endotoxin (OR=6.146,95%CI=4.091-8.226,P=0.001),procalcitonin(PCT) (OR=6.513,95%CI=4.365-8.210,P=0.005) and cardiac troponin I(cTnI) (OR=1.144,95%CI=1.001-2.150,P=0.047) were independent predictors of BNP≥2400 ng/L in patients with Gram-negative sepsis.Pearson correlation analysis showed that BNP was negatively correlated with CI(R=-0.514,P<0.001)and LVEF (R=-0.552,P<0.001),whereas positively correlated with lactic acid (R=0.265,P=0.032),cTnI (R=0.204, P=0.036),PCT(R=0.801,P<0.001),and endotoxin(R=0.765,P<0.001). Conclusions In septic patients with Gram-negative bacterial infection,LVEF,CI,lactic acid,cTnI,endotoxin and PCT are all independent risk factors for the significant increase of BNP,and endotoxin and PCT were more significantly correlated with BNP increase.Endotoxin and inflammatory reaction may be the more important stimulators of BNP increase in septic patients with Gram-negative bacterial infection.

Effect of incineration temperature on chromium speciation in real chromium-rich tannery sludge under air atmosphere.

As a hazardous waste, the disposal of chromium enriched tannery sludge has attracted increasing public concern due to its potential adverse risks towards the environment. And incineration is considered to be an effective method to stabilize heavy metals, like Cr, in solid phase during tannery sludge treatment. In this study, real chromium enriched tannery sludge without pre-treatment was incinerated at 300°C-1200 °C under air atmosphere to investigate the transformation of chromium speciation. Here detailed thermal behavior, phase transformation and chromium speciation were characterized by TG-DSC, XRD and XPS, respectively. Experimental results show that content of Cr(VI) increases gradually with the increase of temperature from 300 °C to 500 °C and reaches a maximal level of 46% total Cr at 500 °C, with different Cr(VI) species of CaCrO4, MgCrO4 and Cr5O12. However, the content of Cr(VI) decreases gradually with the further increase of temperature, with only about 5% Cr(VI) at high temperature of 1200 °C, due to formation of Cr(III) species of Cr2O3 crystallite and MgCr2O4 spinel. Besides, a growing number of hexagonally shaped flake-like crystallite Cr2O3 can be discovered from characterization results of XRD and SEM. Finally, the reduction of CaCrO4 to Cr2O3 in the presence of SiO2 is thermodynamically feasible over 700 °C, indicating possible transformation of Cr(VI) to Cr(III) through controlled incineration temperature.

Decision-making among the substitute decision makers in intensive care units: An investigation of decision control preferences and decisional conflicts.

AIMS: To explore decision control preferences and decisional conflicts and to analyse their association among the surrogate decision makers in the intensive care unit. DESIGN: The study carried out a cross-sectional survey among the surrogates. METHODS: The participants were 115 surrogate decision makers of critical patients, from August to September 2019. A Chi-squared test and logistic regression were used to assess decision control preferences and decisional conflicts, and Spearman's rank correlation coefficient was employed to examine their association. RESULTS: Of the 115 surrogate decision makers, 51.3% preferred a collaborative role, and 63.48% were somewhat unsure about making decisions. Logistic regression analysis identified decision control preferences was associated with surrogates' age, education level, and personality traits, while decisional conflicts was associated with surrogates' age, education level, character, medical expense burden, and Acute Physiology and Chronic Health Evaluation-II score. Cohen's kappa statistics showed a bad concordance of decision-making expectations and actuality, with kappa values of 0.158 (p < .05). Wherein surrogates who experienced discordance between their preferred and actual roles, have relatively higher decisional conflicts. CONCLUSION: This study identified individual differences of surrogate decision makers in decision control preferences and decisional conflicts. These results imply that incorporation of the individual decision preferences and communication styles into care plans is an important first step to develop high quality decision support. IMPACT: This research is a contribution to the limited study on decision control preferences and decisional conflicts among surrogate decision makers of critically ill patients. Moreover based on the investigation of understanding the status and related factors of decision preferences and decisional conflicts set the stage for developing effective decision support interventions.

Emergence Delirium in Elderly Patients as a Potential Predictor of Subsequent Postoperative Delirium: A Descriptive Correlational Study.

PURPOSE: This study aimed to investigate the incidence of emergence delirium (ED) in elderly patients under general anesthesia and to determine the correlation between ED and delirium at five subsequent postoperative days. DESIGN: This research is a descriptive correlational study. METHODS: A total of 168 aged patients undergoing elective general anesthesia were recruited from a comprehensive tertiary teaching hospital with 2,400 beds in Southern China from April 2018 to September 2018. The Nursing Delirium Screening Scale was used to assess delirium at 30 and 60 minutes after extubation or on discharge from the postanesthesia care unit. Patients were assessed for delirium at postoperative days one through five using the same method. Patients' demographic information, including cognitive function, were collected. FINDINGS: Among the 168 aged patients, 58 suffered from ED (34.5%), including the 79.3% for the 46 patients who experienced postoperative delirium (POD). A positive correlation existed between ED and POD (χ2 = 111.744; P < .01). Logistic regression analysis included seven variables: age, preoperative Mini-Mental State Examination score, underlying diseases, American Society of Anesthesiologists grade, surgery duration, postoperative complications, and the presence of ED. Age and ED were concluded to be independent predictive factors of POD. CONCLUSIONS: ED in the first hour after tracheal tube removal is a predictor of delirium at five subsequent postoperative days. Accurate and timely assessment of recovery period can effectively guide the treatment and rehabilitation of POD and maximize prevention of adverse consequences.

Neurodevelopmental toxicity assessments of alkyl phenanthrene and Dechlorane Plus co-exposure in zebrafish.

Alkyl phenanthrene (A-Phen) and Dechlorane Plus (DP) are ubiquitous environmental pollutants that widely co-exist in the environment. It has been established that both A-Phen and DP elicit neurotoxicity, but the potential interactive toxicity of these contaminants is not well-known. To determine whether a mixture of A-Phen and DP would exhibit interactive effects on neurodevelopment, we co-exposed 3-methylphenanthrene (3-MP), a representative of A-Phen, with DP. Our results illustrated that exposure to 5 or 20 µg/L 3-MP alone or in combination with 60 µg/L DP caused neurobehavioral anomalies in zebrafish. In accordance with the behavioral deficits, 3-MP alone or co-exposed with DP significantly decreased axonal growth of secondary motoneurons, altered intracellular Ca2+ homeostasis and induced cell apoptosis in the muscle of zebrafish. Additionally, 3-MP alone or co-exposed with DP significantly increased reactive oxygen species (ROS) and the mRNA levels of apoptosis-related genes. These findings indicate that 3-MP alone or co-exposed with DP induces neurobehavioral deficits through the combined effects on neuronal connectivity and muscle function. Chemical analysis revealed significant increases in 3-MP and DP bioaccumulation in zebrafish co-exposed with 3-MP and DP. Elevated bioaccumulation resulting from mixture exposure may represent a significant contribution of the synergistic effects observed in combined chemical exposure.

TCR repertoire profiling of tumors, adjacent normal tissues, and peripheral blood predicts survival in nasopharyngeal carcinoma.

The T-cell immune responses in nasopharyngeal carcinoma patients have been extensively investigated recently for designing adoptive immunotherapy or immune checkpoint blockade therapy. However, the distribution characteristics of T cells associated with NPC pathogenesis are largely unknown. We performed deep sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue from 15 NPC patients and peripheral blood from 39 NPC patients, 39 patients with other nasopharyngeal diseases, and 33 healthy controls. We found that a lower diversity of TCR repertoire in tumors than paired tissues or a low similarity between the paired tissues was associated with a poor prognosis in NPC. A more diverse TCR repertoire was identified in the peripheral blood of NPC patients relative to the controls; this was related to a significant decrease in the proportion of high-frequency TCR clones in NPC. Higher diversity in peripheral blood of NPC patients was associated with a worse prognosis. Due to the peculiarity of the Vß gene usage patterns in the peripheral blood of NPC patients, 15 Vß genes were selected to distinguish NPC patients from controls by the least absolute shrinkage and selection operator analysis. We identified 11 clonotypes shared by tumors and peripheral blood samples from different NPC patients, defined as "NPC-associated" that might have value in adoptive immunotherapy. In conclusion, we here report the systematic and overall characteristics of the TCR repertoire in tumors, adjacent normal tissues, and peripheral blood of NPC patients. The data obtained may be relevant to future clinical studies in the setting of immunotherapy for NPC patients.

Circulating CD8+ T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients.

PURPOSE: CD8+ T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8+ T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy. EXPERIMENTAL DESIGN: We applied a high-throughput TCR ß-chain sequencing method to characterize the CD8+ T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8+ T-cell repertoire during chemotherapy were analyzed. RESULTS: We found that the HEC ratios of the CD8+ T-cell repertoires from HER2+ breast cancer patients were significantly higher than those of HER2- patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8+ T cells. Several Vß and CDR3 motifs preferentially used in HER2+ patients were identified. Besides, we found that the circulating CD8+ T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8+ T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response. CONCLUSIONS: Although functional studies of clonally expanded CD8+ T-cell populations are clearly required, our results suggest that the circulating CD8+ T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.