Advances in gut-brain organ chips.

The brain and gut are sensory organs responsible for sensing, transmitting, integrating, and responding to signals from the internal and external environment. In-depth analysis of brain-gut axis interactions is important for human health and disease prevention. Current research on the brain-gut axis primarily relies on animal models. However, animal models make it difficult to study disease mechanisms due to inherent species differences, and the reproducibility of experiments is poor because of individual animal variations, which leads to a significant limitation of real-time sensory responses. Organ-on-a-chip platforms provide an innovative approach for disease treatment and personalized research by replicating brain and gut ecosystems in vitro. This enables a precise understanding of their biological functions and physiological responses. In this article, we examine the history and most current developments in brain, gut, and gut-brain chips. The importance of these systems for understanding pathophysiology and developing new drugs is emphasized throughout the review. This article also addresses future directions and present issues with the advancement and application of gut-brain-on-a-chip technologies.

Progress in SARS-CoV-2, diagnostic and clinical treatment of COVID-19.

Background: Corona Virus Disease 2019(COVID-19)is a global pandemic novel coronavirus infection disease caused by Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although rapid, large-scale testing plays an important role in patient management and slowing the spread of the disease. However, there has been no good and widely used drug treatment for infection and transmission of SARS-CoV-2. Key findings: Therefore, this review updates the body of knowledge on viral structure, infection routes, detection methods, and clinical treatment, with the aim of responding to the large-section caused by SARS-CoV-2. This paper focuses on the structure of SARS-CoV-2 viral protease, RNA polymerase, serine protease and main proteinase-like protease as well as targeted antiviral drugs. Conclusion: In vitro or clinical trials have been carried out to provide deeper thinking for the pathogenesis, clinical diagnosis, vaccine development and treatment of SARS-CoV-2.

Prognosis prediction of procalcitonin within 24 h for acute diquat poisoning.

BACKGROUND: To explore the predictive value of procalcitonin (PCT) within 24 h after poisoning for prognosis of acute diquat poisoning. METHODS: This retrospective study included acute diquat poisoning patients in the Nanyang City Hospital between May 2017 and July 2021. RESULTS: Among the 45 patients included, 27 survived. The maximum PCT value within 24 h after poisoning was significantly higher in the non-survival patients [9.65 (2.63, 22.77) vs. 0.15 (0.10, 0.50) µg/mL, P < 0.001] compared to the survival patients. The area under the ROC curve (AUC) indicated that the maximum PCT value within 24 h had a good predictive value (AUC = 0.905, 95% CI: 0.808-1.000) compared to ingested quantity (AUC = 0.879, 95% CI: 0.776-0.981), serum creatinine (AUC = 0.776, 95% CI: 0.640-0.912), or APACHE II score (AUC = 0.778, 95% CI: 0.631-0.925). The predictive value of maximum PCT value within 24 h was comparable with blood lactate (AUC = 0.904, 95%CI: 0.807-1.000). CONCLUSIONS: The maximum PCT value within 24 h after poisoning might be a good predictor for the prognosis of patients with acute diquat poisoning.

Development of a multi-recombinase polymerase amplification assay for rapid identification of COVID-19, influenza A and B.

The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.

Methods of Respiratory Virus Detection: Advances towards Point-of-Care for Early Intervention.

Respiratory viral infections threaten human life and inflict an enormous healthcare burden worldwide. Frequent monitoring of viral antibodies and viral load can effectively help to control the spread of the virus and make timely interventions. However, current methods for detecting viral load require dedicated personnel and are time-consuming. Additionally, COVID-19 detection is generally relied on an automated PCR analyzer, which is highly instrument-dependent and expensive. As such, emerging technologies in the development of respiratory viral load assays for point-of-care (POC) testing are urgently needed for viral screening. Recent advances in loop-mediated isothermal amplification (LAMP), biosensors, nanotechnology-based paper strips and microfluidics offer new strategies to develop a rapid, low-cost, and user-friendly respiratory viral monitoring platform. In this review, we summarized the traditional methods in respiratory virus detection and present the state-of-art technologies in the monitoring of respiratory virus at POC.

Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway.

Given the poor prognosis of unresectable advanced gastric cancer (GC), novel therapeutic strategies are needed. The mitogen-activated protein kinase (MAPK) signaling cascade, the most frequently activated pathway in GC, plays an important role in tumorigenesis and metastasis. The MAPK/extracellular signal-regulated kinase (ERK) pathway is an attractive therapeutic target for GC. In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC.

Microchips for detection of exfoliated tumor cells in urine for identification of bladder cancer.

Bladder cancer (BC) is a common malignancy, and it accounts for one of the highest management costs among urogenital cancers. As a non-invasive method, urine cytology plays an important role in the detection of exfoliated tumor cells (ETCs) for early diagnosis of BC. However, urine cytology suffers from its low sensitivity and reliance on microscopic examination. To address this issue, an integrated filtration device was developed with a pore size of 5 µm that isolated and enriched ETCs from discarded urine samples, and then quantified ETCs using a microchip ELISA method. The results revealed that the number of urinary ETCs from BC patients (n = 35) was obviously higher than the number of ETCs from healthy donors (n = 20). The ROC curve showed that the integrated filtration microfluidic device had a sensitivity of 77.1% when the specificity was set at 90% in identifying BC patients. Thus, the integrated filtration device holds great potential for the screening of BC or the follow-up analysis of treatment efficacy in point-of-care (POC) settings.

Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing.

Cancer poses a great health threat to both developed and developing countries, and anti-cancer drugs are of important interest for improved clinical outcomes. Although tumor-on-a-chip technologies offer a feasible approach to screening drug toxicity, their capability to mimic the native tumor microenvironment (TME) is still limited. For better mimicry of the TME, we developed a biomimetic three-dimensional (3D) liver tumor-on-a-chip with the integration of essential components derived from decellularized liver matrix (DLM) with gelatin methacryloyl (GelMA) in a microfluidics-based 3D dynamic cell culture system. The biomimetic liver tumor-on-a-chip based on the integration of DLM components with GelMA, as opposed to GelMA only, had an increased capability to maintain cell viability and to enhance hepatocyte functions under flow conditions. The improved performance of the DLM-GelMA-based tumor-on-a-chip may be attributed to the provision of biochemical factors (e.g., growth factors), the preservation of scaffold proteins, and the reestablishment of biophysical cues (e.g., stiffness and shear stress) for better recapitulation of the 3D liver TME. Furthermore, this DLM-GelMA-based tumor-on-a-chip exhibited linear dose-dependent drug responses to the toxicity of acetaminophen and sorafenib. Taken together, our study demonstrates that the DLM-GelMA-based biomimetic liver tumor-on-a-chip better mimics the in vivo TME and holds great promise for a breadth of pathological and pharmacological studies.

Tumor-on-a-chip platforms for assessing nanoparticle-based cancer therapy.

Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP-based cancer therapy techniques, and then present the latest advances in 'tumor-on-a-chip' platforms that can potentially facilitate clinical translation of NP-based cancer therapies.

A decade of progress in liver regenerative medicine.

Liver diseases can be caused by viral infection, metabolic disorder, alcohol consumption, carcinoma or injury, chronically progressing to end-stage liver disease or rapidly resulting in acute liver failure. In either situation, liver transplantation is most often sought for life saving, which is, however, significantly limited by severe shortage of organ donors. Until now, tremendous multi-disciplinary efforts have been dedicated to liver regenerative medicine, aiming at providing transplantable cells, microtissues, or bioengineered whole liver via tissue engineering, or maintaining partial liver functions via extracorporeal support. In both directions, new compatible biomaterials, stem cell sources, and bioengineering approaches have fast-forwarded liver regenerative medicine towards potential clinical applications. Another important progress in this field is the development of liver-on-a-chip technologies, which enable tissue engineering, disease modeling, and drug testing under biomimetic extracellular conditions. In this review, we aim to highlight the last decade's progress in liver regenerative medicine from liver tissue engineering, bioartificial liver devices (BAL), to liver-on-a-chip platforms, and then to present challenges ahead for further advancement.

Isolation, identification and phenotypic and molecular characterization of pathogenic Vibrio vulnificus isolated from Litopenaeus vannamei.

The morphology and the drug sensitivity of the strain GYX2014-1 isolated from the hepatic pancreatic tissue of moribund Litopenaeus vannamei were evaluated by conventional culture characteristics, physical and chemical characteristics, and molecular biology methods. Detection of extracellulase and hemolysin activity shows that the isolated GYX2014-1 has protease, lipase, gelatinase activity, but none of amylase, or lecithinase activity. The 16S rRNA gene (GenBank accession number: KT781675) was analyzed, and a phylogenetic tree analysis showed that the isolated pathogen was most closely related to V. vulnificus (GenBank accession number: NR 118570)-a match of more than 99%. The phenotypic traits and molecular biology of isolated bacteria, determined their identity as Vibrio vulnificus (V. vulnificus). In addition, artificially infected L. vannamei with Vibrio vulnificus appeared with the same disease symptoms as those of naturally infected shrimp. Drug sensitivity tests showed that V. vulnificus is highly sensitive to fosfomycin, cefradine and sinomin, and was resistant to penicillin, amikacin and kanamycin. This experiment is the first to separate V. vulnificus from L. vannamei, and the findings of this study can be used as a reference for disease control and health management.

Nanomaterial-based biosensors for measurement of lipids and lipoproteins towards point-of-care of cardiovascular disease.

Cardiovascular disease (CVD) has become the primary cause of global deaths and inflicts an enormous healthcare burden on both developed and developing countries. Frequent monitoring of CVD-associated risk factors such as the level of lipids (e.g., triglyceride (TG) and total cholesterol (TC)) and lipoproteins (e.g., low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) can effectively help prevent disease progression and improve clinical outcomes. However, measurement of these risk factors is generally integrated into an automated analyzer, which is prohibitively expensive and highly instrument-dependent for routine testing in primary care settings. As such, a variety of rapid, simple and portable nanomaterial-based biosensors have been developed for measuring the level of lipids (TG and TC) and lipoproteins (LDL and HDL) towards the management of CVD at the point-of-care (POC). In this review, we first summarize traditional methods for measurement of lipids and lipoproteins, and then present the latest advances in developing nanomaterial-based biosensors that can potentially monitor the risk factors of CVD at the POC.

An Integrated Double-Filtration Microfluidic Device for Detection of Extracellular Vesicles from Urine for Bladder Cancer Diagnosis.

Extracellular vesicles (EVs) are present in a variety of bodily fluids and they play an important role in cellular communications and signal transduction mechanisms. Studies have shown that the number of EVs and EV-associated biomarkers (i.e., proteins, nucleic acids and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for EV isolation, it is not practical for clinical settings. Here, we developed an integrated double-filtration device that isolated and enriched EVs from urine, and subsequently detected/quantified EVs from urine via microchip ELISA. Results showed that the concentration of EVs was significantly elevated compared to healthy controls. Receiver operating characteristic analysis demonstrated that this integrated EV quantification device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and eight healthy controls). Thus, this integrated device shows great potential to supplement urine cytology for diagnosis of bladder cancer in point-of-care (POC) settings.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer.

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30-200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings.

Advances in addressing technical challenges of point-of-care diagnostics in resource-limited settings.

The striking prevalence of HIV, TB and malaria, as well as outbreaks of emerging infectious diseases, such as influenza A (H7N9), Ebola and MERS, poses great challenges for patient care in resource-limited settings (RLS). However, advanced diagnostic technologies cannot be implemented in RLS largely due to economic constraints. Simple and inexpensive point-of-care (POC) diagnostics, which rely less on environmental context and operator training, have thus been extensively studied to achieve early diagnosis and treatment monitoring in non-laboratory settings. Despite great input from material science, biomedical engineering and nanotechnology for developing POC diagnostics, significant technical challenges are yet to be overcome. Summarized here are the technical challenges associated with POC diagnostics from a RLS perspective and the latest advances in addressing these challenges are reviewed.