Promoting patient-centered care in CAR-T therapy for hematologic malignancy: a qualitative meta-synthesis.

BACKGROUND: CAR-T therapy has emerged as a potentially effective treatment for individuals diagnosed with hematologic malignancies. Understanding patients' unique experiences with this therapeutic approach is essential. This knowledge will enable the development of tailored nursing interventions that align with the increasing importance of patient-centered care. OBJECTIVE: To examine and synthesize qualitative data on patients and their family caregivers' experiences during the treatment journey. DESIGN: We conducted a systematic review and qualitative meta-synthesis. Eligible studies contained adult patient or family caregiver quotes about experiences of CAR-T therapy, published in English or Chinese in a peer-reviewed journal since 2015. Data sources included MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, Scopus, Cochrane Library, CNKI, and WanFang. METHODS: Systematic search yielded 6373 identified articles. Of these, 12 reports were included in the analysis, which covered 11 separate studies. Two reviewers independently extracted data into NVIVO 12.0. Qualitative meta-synthesis was performed through line-by-line coding of full text, organization of codes into descriptive themes, and development themes. RESULTS: The qualitative meta-synthesis yielded eight primary themes. Noteworthy revelations from patients and their family caregivers regarding the CAR-T therapy journey encompassed various aspects. Prior to CAR-T therapy, patients experienced a lack of actual choice, struggled with expectations for treatment outcomes, and encountered intricate emotional experiences. During or immediately after CAR-T therapy, patients reported both comfortable and uncomfortable experiences. Additionally, patients emphasized that concerns regarding treatment efficacy and adverse reactions intensified treatment-related distress. After CAR-T therapy, significant changes were observed, and the burden of home-based rehabilitation. Additionally, we found factors contributed to the high CAR-T therapy cost. CONCLUSIONS: To ensure the safety and sustainability of CAR-T therapy, it is crucial to address the physical and psychological aspects of the patient's experience. Effective communication and comprehensive management are highly valued by patients and their caregivers. Further research should investigate ways to reduce burdens and develop self-management education programs for patients and their families.

Mediterranean diet related to 3-year incidence of cognitive decline: results from a cohort study in Chinese rural elders.

OBJECTIVE: This study aims to examine the effect of the Mediterranean diet (MeDi) on cognitive decline among the Chinese elderly with a 3-year follow-up. METHODS: This study is divided into two waves: wave-1 January 2019 to June 2019 (n = 2313); wave-2 January 2022 to March 2022 (n = 1648). MeDi scores were calculated from the Mediterranean Diet Adherence Screener (MEDAS), with the scoring of low compliance (0-6 points) and high compliance (7-14 points). The Mini-Mental State Examination (MMSE) was used to assess cognitive function. An MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between MeDi score and cognitive decline were analyzed by linear regression models or Binary logistic regression. RESULTS: During the 3-year follow-up, 23.8% of patients exhibited cognitive decline. The study revealed a significant difference in MMSE score changes between low and high MeDi adherence groups (p < 0.001). MeDi score was negatively correlated with cognitive deterioration (ß = -0.020, p = 0.026). MeDi score was only negatively associated with cognitive decline in the female subgroup aged ≥65 years (ß = -0.034, p = 0.033). The food beans (OR = 0.65, 95%CI:0.51, 0.84), fish (OR = 0.72, 95%CI:0.54, 0.97), and cooked vegetables (OR = 0.68, 95%CI:0.53, 0.84) were protective factors for cognitive decline. CONCLUSIONS: This study suggests that greater adherence to the MeDi is linked to a reduced risk of cognitive decline in elderly people. However, this is found only in women who are 65 years old or older. It also found long-term adherence to beans, fish, and vegetables are more effective in improving cognitive function.

Approximately half of the nursing students confirmed their willingness to participate in caring for older people: a systematic review and meta-analysis.

BACKGROUND: Global population aging poses a significant global challenge, necessitating an increased demand for proficient caregivers specialized in elderly care. In our study, a systematic review and meta-analysis were conducted to synthesize the evidence concerning nursing students' willingness to participate in caring for older people. METHODS: Eligibility criteria focused on cross-sectional studies involving nursing students' willingness to participate in caring for older people and were reported in English or Chinese. PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WANFANG databases were searched from inception until July 24, 2022. The methodological quality assessment in the included studies was evaluated using the AHRQ instrument. The pooled effects of the nursing students' willingness to participate in caring for older people were computed using a random-effects model. Funnel plots and Egger's test were employed to evaluate publication bias. Meta-regression and subgroup analysis were performed to explore the sources of heterogeneity. Sensitivity analysis was conducted to verify the robustness of the meta-analysis findings. All statistical tests were conducted with Stata 16.0 software. RESULTS: A total of 68 studies of medium or high quality met the eligibility criteria, involving 30,328 nursing students. The rate of nursing students' willingness to participate in caring for older people was 49.0% (95% CI = 46-53%, I2 = 98.1%, P = 0.000). The results of meta-regression analysis showed that the following four predictor variables were significantly associated with nursing students' willingness to participate in caring for older people: experience of living with and caring for older people, nursing as their first choice and their year-level in education, respectively. Subgroup analyses for these four predictor variables revealed the following pooled estimates of nursing students' willingness: having experience of living with older people (0.54, 95% CI = 0.46-0.62) vs. no such experience (0.38, 95% CI = 0.30-0.46), having experience of caring for older people (0.55, 95% CI = 0.48-0.63) vs. no such experience (0.38, 95% CI = 0.30-0.46), nursing as their first choice (0.54, 95% CI = 0.51-0.58) vs. not their first choice (0.44, 95% CI = 0.35-0.53), being in the first year of nursing education (0.44, 95% CI = 0.34-0.55), second year (0.45, 95% CI = 0.34-0.56), and third and fourth year (0.62, 95% CI = 0.53-0.71). CONCLUSION: The study found that approximately half of the nursing students confirmed their willingness to participate in caring for older people.The present study can serve as a resource for policymakers to increase the willingness of nursing students to participate in caring for older people.

Radioactive and Fluorescent Dual Modality Cysteine Cathepsin B Activity-Based Probe for Cancer Theranostics.

Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study sets out to develop and evaluate an activity-based multimodality theranostic agent targeting CTS-B for cancer imaging and therapy. A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with 68Ga and 90Y to produce 68Ga-BMX2 for multimodality imaging and 90Y-BMX2 for radiation therapy. The affinity and specificity of BMX2 binding with the CTS-B enzyme were determined by fluorescent western blots using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG, with CA074 as the CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement were also performed. Then, in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of 90Y-BMX2 was tested. BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B is time-dependent and enzyme concentration-dependent. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and 68Ga-BMX2. In vivo optical and PET imaging showed a high tumor uptake of BMX2 and 68Ga-BMX2 and accumulation for more than 24 h. 90Y-BMX2 could significantly inhibit HeLa tumor growth. The development of 68Ga/90Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostics in the future.

Anastomotic occlusion after laparoscopic low anterior rectal resection: a rare case study and literature review.

BACKGROUND: With the development of laparoscopic techniques and the broad clinical application of various anastomotic types, anal-preserving low anterior rectal resection and ultra-low anterior rectal resection have been popularized. Some patients with rectal cancer have retained their anus and improved their quality of life. Nevertheless, the incidence of postoperative anastomotic stenosis remains high, and anastomotic occlusion is even rarer. CASE PRESENTATION: We report a case of anastomotic occlusion in a patient with rectal cancer, which occurred after undergoing laparoscopic low anterior rectal resection + prophylactic terminal ileal fistulation at our department. Under endoscopy, we used a small guidewire to break through the occluded anastomosis, thereby finding the lacuna. After endoscopic balloon dilation, digital anal dilatation, and continuous dilator-assisted dilation, the desired efficacy was achieved, ultimately recovering ileal stoma. Postoperative follow-up condition was generally acceptable, without symptoms like abdominal pain, bloating, or difficulty in defecation. CONCLUSION: Numerous factors cause postoperative anastomotic stenosis in patients with rectal cancer. Complete occlusion of anastomosis occurs relatively rare in clinical practice, and is challenging to treat. This case was our first attempt to remove the anastomotic occlusion successfully, which avoided re-operation or pain from the permanent fistula.

A Network Model for Detecting Marine Floating Weak Targets Based on Multimodal Data Fusion of Radar Echoes.

Due to the interaction between floating weak targets and sea clutter in complex marine environments, it is necessary to distinguish targets and sea clutter from different dimensions by designing universal deep learning models. Therefore, in this paper, we introduce the concept of multimodal data fusion from the field of artificial intelligence (AI) to the marine target detection task. Using deep learning methods, a target detection network model based on the multimodal data fusion of radar echoes is proposed. In the paper, according to the characteristics of different modalities data, the temporal LeNet (T-LeNet) network module and time-frequency feature extraction network module are constructed to extract the time domain features, frequency domain features, and time-frequency features from radar sea surface echo signals. To avoid the impact of redundant features between different modalities data on detection performance, a Self-Attention mechanism is introduced to fuse and optimize the features of different dimensions. The experimental results based on the publicly available IPIX radar and CSIR datasets show that the multimodal data fusion of radar echoes can effectively improve the detection performance of marine floating weak targets. The proposed model has a target detection probability of 0.97 when the false alarm probability is 10-3 under the lower signal-to-clutter ratio (SCR) sea state. Compared with the feature-based detector and the detection model based on single-modality data, the new model proposed by us has stronger detection performance and universality under various marine detection environments. Moreover, the transfer learning method is used to train the new model in this paper, which effectively reduces the model training time. This provides the possibility of applying deep learning methods to real-time target detection at sea.

Instrumentation-Compact Digital Microfluidic Reaction Interface-Extended Loop-Mediated Isothermal Amplification for Sample-to-Answer Testing of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is usually spread via consumption of contaminated seafood and causes vibriosis. By combination of digital microfluidic (DMF) and loop-mediated isothermal amplification (LAMP), we provided an automated instrumentation-compact DMF-LAMP device for sample-to-answer detection of V. parahaemolyticus. For the first time, how much the proper mixing might facilitate the DMF-LAMP process is explored. The results illustrated that increasing the number of flow configurations and decreasing the fluid-reversibility will extend the interfacial surface available for diffusion-based mass transfer within a droplet microreactor, thus contributing to the overall amplification reaction rate. Noticeably, the DMF-LAMP amplification plateau time is shortened by proper mixing, from 60 min in static mixing and traditional bulk LAMP to 30 min in 2-electrode mixing and 15 min in 3-electrode mixing. The device achieved much higher detection sensitivity (two copies per reaction) than previously reported devices. V. parahaemolyticus from spiked shrimps is detected by Q-tip sampling associated with 3-electrode mixing DMF-LAMPs. The detectable signal occurs within only 3 min at a higher concentration and, at most, is delayed to 18 min, with a detection limit of <0.23 × 103 CFU/g. Thus, the developed DMF-LAMP device demonstrates potential for being used as a sample-to-answer system with a quick analysis time, high sensitivity, and sample-to-answer format.

An integrated digital microfluidic bioreactor for fully automatic screening of microalgal growth and stress-induced lipid accumulation.

Algae are the promising feedstock of biofuel. The screening of competent species and proper fertilizer supply is of the most important tasks. To accelerate this rather slow and laborious step, we developed an integrated high-throughput digital microfluidic (DMF) system that uses a discrete droplet to serve as a microbioreactor, encapsulating microalgal cells. On the basis of fundamental understanding of various droplet hydrodynamics induced by the existence of different sorts of ions and biological species, incorporation of capacitance-based position estimator, electrode-saving-based compensation, and deterministic splitting approach, was performed to optimize the DMF bioreactor. Thus, it enables all processes (e.g., nutrient gradient generation, algae culturing, and analyzing of growth and lipid accumulation) occurring automatically on-chip especially in a high-fidelity way. The ability of the system to compare different microalgal strains on-chip was investigated. Also, the Chlorella sp. were stressed by various conditions and then growth and oil accumulation were analyzed and compared, which demonstrated its potential as a powerful tool to investigate microalgal lipid accumulation at significantly lower laborites and reduced time.

A three-dimensional pinwheel-shaped paper-based microfluidic analytical device for fluorescence detection of multiple heavy metals in coastal waters by rational device design.

Here, we present the rational design of a pinwheel-shaped three-dimensional microfluidic paper-based analytical device (3D-µPAD) for specific, sensitive and multiplexed detection of heavy metals in coastal waters. A more homogeneous permeation of fluids along the chip than common design, even under unskilled performance, has been achieved by the elaborate chip design of the hydrostatic balancing inlet port and uniformly stressed reversible sealing. With the combination of ion imprinted polymer grafted CdTe quantum-dots and fluid accumulation pad, 4 metals (Cu2+, Cd2+, Pb2+, and Hg2+) in 1 analysis and 25-fold enrichment for each metal can be simultaneously performed within 20 min, with detection limits of 0.007-0.015 µg/L. It has the ability to selectively recognize these 4 metals in mixtures and immunizing to interferences from components found in coastal waters, which provided results that were in agreement with values gained from atomic absorption. The inexpensive and portable nature as well as the highly sensitive and flexible performance of the new developed 3D-µPAD could make it attractive as an on-site testing approach for marine environmental monitoring.

Design, synthesis and anti-Alzheimer's disease activity study of xanthone derivatives based on multi-target strategy.

A series of xanthone derivatives were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). In vitro studies showed all xanthone derivatives had good metal chelating property and exhibited selective inhibitory activity against Acetylcholinesterase (AChE). In particular, compound 2a showed the highest inhibitory activity against AChE, and the IC50 value was (0.328 ± 0.001) µM, which was comparable to tacrine. Kinetic analysis and molecular docking studies indicated that these derivatives targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of AChE. Moreover, all derivatives showed higher anti-oxidative activity than vitamin C. Furthermore, copper complex had higher anti-AChE activity and antioxidant activity. Thus, these xanthone derivatives are potential multi-targeted-directed ligands for further development for the treatment of AD.

Strain induced spin-splitting and half-metallicity in antiferromagnetic bilayer silicene under bending.

Searching for half-metals in low dimensional materials is not only of scientific importance, but also has important implications for the realization of spintronic devices on a small scale. In this work, we show theoretically that simple bending can induce spin-splitting in bilayer silicene. For bilayer silicene with Bernal stacking, the monolayer has a long range ferromagnetic spin order and between the two monolayers, the spin orders are opposite, giving rise to an antiferromagnetic configuration for the ground state of the bilayer silicene. Under bending, the antiferromagnetic spin order is retained but the energetic degeneracy of opposite spin states is lifted. Due to the unusual deformation potentials of the conduction band minimum (CBM) and valence band maximum (VBM) as revealed by density-functional theory calculations and density-functional tight-binding calculations, this spin-splitting is nearly proportional to the degree of bending deformation. Consequently, the spin-splitting can be significant and the desired half-metallic state may emerge when the bending increases, which has been verified by direct simulation of the bent bilayer silicene using the generalized Bloch theorem. Our results hint that bilayer silicene may be an excellent candidate for half-metallicity.

Analysis of the status quo of the Elderly's demands of medical and elderly care combination in the underdeveloped regions of Western China and its influencing factors: a case study of Lanzhou.

BACKGROUND: This study aims to analyse the current demand by senior citizens in Lanzhou, China for a combination of medical and elderly care services and to identify the factors influencing their needs. METHODS: 7500 participants aged 60 or above living in Lanzhou, China, were recruited, a unified questionnaire concerning elderly people's demand for a service combining medical and elderly care has been adopted to survey these subjects. The status quo of the demand of the service combining medical and elderly care and its influencing factors were analysed with the single-factor Chi-square test and multi-factor binomial logistic regression method. RESULTS: 3772 of 7320 older people have the demand for the service combining medical and elderly care, accounting for 53.15% of survey respondents. Many factors are in play, including gender, marital status, degree of education, occupation before retirement, number of children, monthly income, health self-assessment status, endowment insurance type, medical insurance type, current nursing arrangements, old-age demands, self-care ability and the knowledge of combining medical and elderly care and the willingness to pay for the combination of medical and elderly care have statistical significance (P < 0.05) with the elderly's needs, different ages, living styles and the prevalence of chronic diseases, have no statistical significance (P > 0.05) with the elderly's care needs in Lanzhou. The number of children, type of medical insurance and willingness to pay for the combination of medical treatment and nursing care are major influencing factors among the complex factors influencing the elderly's demand for the proposed service. CONCLUSIONS: The low knowledge rate and demand rate, the number of children, the type of medical insurance, and the willingness to pay for the medical-nursing combination service for the elderly in Lanzhou have a great impact on the elderly's demand rate for combining medical and elderly care. Meanwhile, relevant government departments should focus more on the promotion of the endowment model of combining medical and elderly care and provide integrated medical care services by integrating multiple resources, and improving social security.

Application of 18F-FDG PET/CT in evaluation of curative effect and prognosis for small cell lung cancer. / 18F-FDG PET/CT在小细胞肺癌疗效与预后评价中的应用.

Small cell lung cancer belongs to neuroendocrine tumors and is the most malignant one in lung cancer. It possesses clinical features such as rapid growth, easy early metastasis, and poor prognosis. PET/CT is a molecular imaging technique that combines morphological and metabolic imaging. It has been widely used in the diagnosis, staging, treatment planning, efficacy and prognosis evaluation of tumors. This article reviews the efficacy, prognostic parameters, evaluation criteria, possible influencial factors, clinical application and value of 18F-fluorodeoxyglucose (18F-FDG) PET/CT in small cell lung cancer. The accuracy and sensitivity of 18F-FDG PET/CT in small cell lung cancer stage, efficacy and prognosis evaluation are significantly higher than those of traditional imaging methods. Maximal standardized uptake, metabolic tumor volume, and total lesion glycolysis have been applied in efficacy and prognosis prediction, which have important value in developing the personalized treatment and improving the survival for small cell lung cancer patient.

Trichoderma harzianum mitigates salt stress in cucumber via multiple responses.

Trichoderma harzianum T-soybean plays an important role in controlling soybean root rot disease. However, the mechanism by which it improves plant tolerance to salt stress is not clear. In this study, we investigated the possible mechanism of T-soybean in mitigating the damage caused by salt stress in Cucumis sativus L plants. Our results suggest that T-soybean improved salt tolerance of cucumber seedlings by affecting the antioxidant enzymes including peroxidase (POD) (EC 1.11.1.6), polyphenol oxidase (PPO) (EC 1.14.18.1), phenylalanine ammonia-lyase (PAL) (EC 4.3.1.5), catalase (CAT) (EC 1.11.1.6), superoxide dismutase (SOD) (EC 1.15.1.1), ascorbate peroxidase (APX) (EC 1.11.1.11), and glutathione reductase (GR) (EC 1.6.4.2), by increasing the levels of proline, soluble sugars, soluble protein, ascorbic acid (AsA) and chlorophyll as well as improving root activity. Treatment with T-soybean improved the ratio of glutathione (GSH)/oxidized glutathione (GSSG) and AsA/dehydroascorbate (DHA), and up-regulated the expression of CsAPX and CsGR genes involved in the AsA-GSH cycle. In addition, treatment with T-soybean increased the K+ content and K+/Na+ ratio while decreased the Na+ concentration and ethylene level. In summary, the improved salt tolerance of cucumber plants may be due to multiple mechanisms of T-soybean, such as the increase in reactive oxygen species (ROS) scavenging, as well as maintaining osmotic balance and metabolic homeostasis under salt stress.

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile, Exerts Anti-bladder Activities through IGF-1R/STAT3 Signaling.

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile (SYD007) is a small molecule compound that was synthesized according to the structure of diarylamine. In this study, we evaluated the anti-bladder activities of SYD007, and determined its cytotoxic mechanism. We found that SYD007 exerted cytotoxicity to bladder cancer cells. Furthermore, SYD007 induced bladder cancer cell early apoptosis and arrested cell cycle. Mechanistically, SYD007 suppressed phosphorylated signal transducer and activator of transcription 3 (p-STAT3) (Tyr705) level in parallel with increases of p-extracellular signal-regulated kinase (ERK) and p-AKT. SYD007 significantly inhibited insulin-like growth factor 1 (IGF-1)-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in SYD007-treated cells, suggesting that SYD007 acted primarily at a posttranscriptional level. Using molecular docking analysis, SYD007 was identified as an IGF-1R inhibitor. In summary, we reported that SYD007 exerted anti-bladder activities, and these effects were partially due to inhibition of IGF-1R/STAT3 signaling.

Computer-aided design of microfluidic resistive network using circuit partition and CFD-based optimization and application in microalgae assessment for marine ecological toxicity.

We present an automatic design process for microfluidic dilution network towards marine ecological toxicity assessment on microalgae. Based on the hydraulic-electric circuit analogy, we defined an abstract specification using computer-aided designing system. Several approaches, especially circuit partition, were applied to minimize design effort. Computational fluid dynamics (CFD) simulation was exploited to convert the electrics specification to fabrication model. We automatically designed the combinational-mixing-serial dilution microfluidics to generate parallel stepwise gradients for mixing chemicals (binary/ternary/quaternary mixture) using the present algorithm. We critically discussed design rules and evaluated the microfluidic performance by colorimetric analysis. To examine whether these microfluidic chips can be used for toxicity test on microalgae, single and joint toxic effects of heavy metals (copper, mercury, zinc, and cadmium) were examined on line. In all cases, dose-related toxic responses were successfully detected. These results provided a solution for designing resistive network using circuit partition and CFD-based optimization and a route to develop a promising user-friendly alternative for microalgae bioassays as well as cell-based screening experiments in risk assessment.

[Benign metastasizing leiomyoma: A case report andliterature review].

Benign metastasizing leiomyoma (BML) often occurs in women with a history of uterine leiomyoma at the childbearing age. At the same time, BML cases with multiple sites of metastatic lesions are extremely rare. A BML patient with multiple metastases of uterine leiomyoma in two lung and lumbar spine after surgery was admitted to Department of Spinal Surgery, Second Xiangya Hospital, Central South University in September 2017. Positron emission tomography/computed tomography (PET/CT) can perform a whole body examination for BML patients, which can find metastases in many parts of the body such as lung, abdominal cavity, pelvic cavity and spine. The PET/CT results are helpful to a comprehensive diagnosis. The imaging and clinical features of BML are now explored in combination with the characteristics of the case and relevant literature reports.

[Health economics analysis for 18F-fluorodeoxyglucose positron-emission tomography compared with computed tomography in lung cancer].

Compared with conventional imaging, 18F-fluorodeoxyglucose positron-emission tomography compared with computed tomography (18F-FDG PET/CT) possesses higher sensitivity and specificity in the diagnosis of solitary pulmonary nodule (SPN) and lung cancer. From the perspective of health economics, PET/CT is more suitable strategy for diagnose of SPN with intermediate probability of malignancy, and has good health economics value in preoperative staging diagnosis and follow-up after radiotherapy and chemotherapy of lung cancer. The evaluation method, effect index and comparison method used in the health economics research of PET/CT for lung cancer diagnosis and treatment are cost-effect analysis, life year and incremental cost-effect ratio, respectively. Case tracking and follow-up was a means of early studies on PET/CT health economics, and in recent years mathematical models are used in most studies.

Development of Microfluidic Dilution Network-Based System for Lab-on-a-Chip Microalgal Bioassays.

Because of the crucial ecological significance of microalgae, microalgal bioassays have become one of the most demanding tests from all classic aquatic toxicity tests in regulatory frameworks. However, conventional algal tests tend to be lab-intensive and time- and space-consuming, and they have not been utilized to their full potential for routine toxicity assessments. Microfluidics should be a user-friendly alternative. Particularly, dilution to generate gradients that are appropriate for screening experiments can be precisely attained by microfluidic network in a simple and cost-/time-/space-saving way. Here, we demonstrate a microfluidics series toward routine microalgal bioassays, including pretest, single, and joint toxicity test. The chip mainly consists of upstream dilution network (single serial dilution module (logarithmic/linear gradient generator) or multiple (binary/ternary/quaternary) mixing serial dilution module) and downstream diffusible culturing module. It allows the processes of chemical liquid dilution and diffusion, microscale microalgal culture, cell stimulation, and online screening to be integrated into a single device. Electric theorems with the aid of EDA (electronic design automation) simulation were innovatively introduced to minimize design effort for such systems. Using the device, microalgae were successfully cultured and stressed on-chip. The simple assay provides multibiological trait assessments of cell division rate, autofluorescence, esterase activity, and mobile capacity. This work showed promise in developing a high-throughput microfluidic platform for microalgal bioassays as well as lab-on-a-chip screening experiments in the cell-based quantitative assessment of environmental health risks.

Differential Expression of PGC1α in Intratumor Redox Subpopulations of Breast Cancer.

Our previous studies indicate that the mitochondrial redox state and its intratumor heterogeneity are associated with invasiveness and metastatic potential in human breast cancer cell models and mouse xenografts. To further study the molecular basis of redox heterogeneity, we obtained the fluorescence images of Fp (oxidized flavoproteins containing flavin adenine dinucleotide, i.e., FAD), NADH (reduced nicotinamide adenine dinucleotide), and the Fp redox ratio (FpR = Fp/(Fp + NADH)) of MDA-MB-231 xenografts by the Chance redox scanner, then isolated the intratumoral redox subpopulations by dissection according to the redox ratio image. A total of 12 subpopulations were isolated from 4 tumors (2-4 locations from each tumor). The 12 subpopulations were classified into 3 FpR groups: high FpR (HFpR, n = 4, FpR range 0.78-0.92, average 0.85), medium FpR (MFpR, n = 5, FpR range 0.39-0.68, average 0.52), and low FpR (LFpR, n = 3, FpR range 0.15-0.28, average 0.20). The RT-PCR (reverse transcription polymerase chain reaction) analysis on these redox subpopulations showed that PGC-1α is significantly upregulated in the HFpR redox group compared to the MFpR group (fold change 2.1, p = 0.008), but not significantly different between MFpR and LFpR groups, or between HFpR and LFpR groups. These results indicate that optical redox imaging (ORI)-based redox subpopulations exhibit differential expression of PGC1α gene and suggest that PGC1α might play a role in redox mediation of breast cancer progression.