Assessing EGFR-mutated NSCLC with bone metastasis: Clinical features and optimal treatment strategy.

BACKGROUND: This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) mutation and to identify the most effective treatment strategy using EGFR-tyrosine kinase inhibitors (TKIs). METHODS: The study included patients with stage IV EGFR-mutated NSCLC who were receiving first-line treatment with EGFR-TKIs between January 2014 and December 2020. These patients were divided into two groups based on the presence or absence of BoM at the time of initial diagnosis. The BoM group was further subdivided based on whether they received denosumab or not. RESULTS: The final analysis included 247 patients. Those with BoM at initial diagnosis had shorter progression-free survival (12.6 vs. 10.5 months, p = 0.002) and overall survival (OS) (49.7 vs. 30.9 months, p = 0.002) compared to those without BoM. There was a difference in the location of metastatic sites between the two groups, with a higher incidence of extrathoracic metastasis in the BoM group (p < 0.001). The incidence of T790M was higher in patients with BoM than in those without (47.4% vs. 33.9%, p = 0.042). Multivariate Cox regression analysis revealed that sequential osimertinib treatment and the addition of antiangiogenic therapy (AAT) and denosumab therapy improved OS in patients with BoM. CONCLUSIONS: The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes.

The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study.

OBJECTIVES: The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting. MATERIALS AND METHODS: Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib. RESULTS: A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years. CONCLUSION: This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions.

iDVEIP: A computer-aided approach for the prediction of viral entry inhibitory peptides.

With the notable surge in therapeutic peptide development, various peptides have emerged as potential agents against virus-induced diseases. Viral entry inhibitory peptides (VEIPs), a subset of antiviral peptides (AVPs), offer a promising avenue as entry inhibitors (EIs) with distinct advantages over chemical counterparts. Despite this, a comprehensive analytical platform for characterizing these peptides and their effectiveness in blocking viral entry remains lacking. In this study, we introduce a groundbreaking in silico approach that leverages bioinformatics analysis and machine learning to characterize and identify novel VEIPs. Cross-validation results demonstrate the efficacy of a model combining sequence-based features in predicting VEIPs with high accuracy, validated through independent testing. Additionally, an EI type model has been developed to distinguish peptides specifically acting as Eis from AVPs with alternative activities. Notably, we present iDVEIP, a web-based tool accessible at http://mer.hc.mmh.org.tw/iDVEIP/, designed for automatic analysis and prediction of VEIPs. Emphasizing its capabilities, the tool facilitates comprehensive analyses of peptide characteristics, providing detailed amino acid composition data for each prediction. Furthermore, we showcase the tool's utility in identifying EIs against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Single-Cell Secretion Analysis via Microfluidic Cell Membrane Immunosorbent Assay for Immune Profiling.

Single-cell multiplexed phenotypic analysis expands the biomarkers for diagnosis, heralding a new era of precision medicine. Cell secretions are the primary measures of immune function, but single-cell screening remains challenging. Here, a novel cell membrane-based assay was developed using cholesterol-linked antibodies (CLAbs), integrating immunosorbent assays and droplet microfluidics to develop a flexible high-throughput single-cell secretion assay for multiplexed phenotyping. CLAb-grafted single cells were encapsulated in water-in-oil droplets to capture their own secretions. Subsequently, the cells were extracted from droplets for fluorescence labeling and screening. Multiple secretions and surface proteins were simultaneously measured from single cells by flow cytometry. To validate the approach, THP-1 cells, THP-1-derived M1 macrophages, and dendritic cells were assayed, indicating the differentiation efficiency of THP-1 cells under different chemical stimulations. Moreover, peripheral blood mononuclear cells from healthy donors under various stimuli showed varied active immune cell populations (6.62-47.14%). The peripheral blood mononuclear cells (PBMCs) of nasopharyngeal carcinoma patients were analyzed to identify a higher percentage of actively cytokine-secreted single cells in the basal state (2.82 ± 1.48%), compared with that in the health donors (0.70 ± 0.29%).

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease.

BACKGROUND: Disease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ. METHODS: For this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan-Meier method, and p-value was calculated using the log-rank test. RESULTS: After 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001). CONCLUSION: Patients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

Graphene oxide aptasensor droplet assay for detection of metabolites secreted by single cells applied to synthetic biology.

Synthetic biology harnesses the power of natural microbes by re-engineering metabolic pathways to manufacture desired compounds. Droplet technology has emerged as a high-throughput tool to screen single cells for synthetic biology, while the challenges in sensitive flexible single-cell secretion assay for bioproduction of high-value chemicals remained. Here, a novel droplet modifiable graphene oxide (GO) aptasensor was developed, enabling sensitive flexible detection of different target compounds secreted from single cells. Fluorophore-labeled aptamers were stably anchored on GO through π-π stacking interactions to minimize the non-specific interactions for low-background detection of target compounds with high signal-to-noise ratios. The assay's versatility was exhibited by adapting aptamer sequences to measure metabolic secretions like ATP and naringenin. To show the case, engineered E. coli were constructed for the bioproduction of naringenin. The high signal-to-noise ratio assay (∼2.72) was approached to precisely measure the naringenins secreted from single E. coli in the droplets. Consequently, secretory cells (Gib) were clearly distinguished from wild-type (WT) cells, with a low overlap in cell populations (∼0%) for bioproduction.

Application of impulse oscillometry to detect interstitial lung disease and airway disease in adults with rheumatoid arthritis.

BACKGROUND: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.

Microbiome analysis of maternal and neonatal microbial communities associated with the different delivery modes based on 16S rRNA gene amplicon sequencing.

OBJECTIVE: With the rising number of cases of non-vaginal delivery worldwide, scientists have been concerned about the influence of the different delivery modes on maternal and neonatal microbiomes. Although the birth rate trend is decreasing rapidly in Taiwan, more than 30 percent of newborns are delivered by caesarean section every year. However, it remains unclear whether the different delivery modes could have a certain impact on the postpartum maternal microbiome and whether it affects the mother-to-newborn vertical transmission of bacteria at birth. MATERIALS AND METHODS: To address this, we recruited 30 mother-newborn pairs to participate in this study, including 23 pairs of vaginal delivery (VD) and seven pairs of caesarean section (CS). We here investigate the development of the maternal prenatal and postnatal microbiomes across multiple body habitats. Moreover, we also explore the early acquisition of neonatal gut microbiome through a vertical multi-body site microbiome analysis. RESULTS AND CONCLUSION: The results indicate that no matter the delivery mode, it only slightly affects the maternal microbiome in multiple body habitats from pregnancy to postpartum. On the other hand, about 95% of species in the meconium microbiome were derived from one of the maternal body habitats; notably, the infants born by caesarean section acquire bacterial communities resembling their mother's oral microbiome. Consequently, the delivery modes play a crucial role in the initial colonization of the neonatal gut microbiome, potentially impacting children's health and development.

A real-world study comparing perioperative chemotherapy and EGFR-tyrosine kinase inhibitors for treatment of resected stage III EGFR-mutant adenocarcinoma.

BACKGROUND: The patient population with stage III non-small-cell lung cancer (NSCLC) is heterogeneous, with varying staging characteristics and diverse treatment options. Despite the potential practice-changing implications of randomized controlled trials evaluating the efficacy of perioperative epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), concerns have been raised due to conflicting overall survival (OS) results. Few real-world studies have examined the survival outcomes of patients with resected EGFR-mutant stage III adenocarcinoma receiving perioperative chemotherapy and EGFR-TKIs. METHODS: In this retrospective observational study, we enrolled patients with resected stage III adenocarcinoma with EGFR mutations between January 2011 and December 2021. Patients were classified into two groups: perioperative chemotherapy and perioperative EGFR-TKIs. Outcomes and prognostic factors were analyzed using Cox proportional hazards regression analysis. RESULTS: Eighty-four patients were enrolled in the analysis. Perioperative EGFR-TKIs led to longer progression-free survival (PFS) than chemotherapy (38.6 versus 14.2 months; p = 0.019). However, only pathological risk factors predicted poor PFS in multivariate analysis. Patients receiving perioperative chemotherapy had longer OS than those receiving EGFR-TKIs (111.3 versus 50.2 months; p = 0.052). Multivariate analysis identified perioperative treatment with EGFR-TKIs as an independent predictor of poor OS (HR: 3.76; 95% CI: 1.22-11.54). CONCLUSION: Our study demonstrates that chemotherapy should be considered in the perioperative setting for high-risk patients, when taking pathological risk factors into consideration, and that optimized sequencing of EGFR-TKIs might be the most critical determinant of OS.

Evaluation of exogenous therapeutic protein activity under confinement and crowding effects.

Dysfunction of intracellular proteins is frequently associated with various diseases, such as cancer. The exogenous proteins in cells are usually assembled with specific configurations due to physiological confinement/crowding to exhibit novel features in the protein structure, folding or conformational stability, distinguished with their behaviors in buffer solutions. Here, we synthesized exogenous proteins under confined/crowded conditions, to explore protein activity within cells. The findings suggested that the confinement and crowding effects on protein activity are heterogeneous; they showed an inhibitory effect on HRP by decreasing Km from ∼9.5- and ∼21.7-fold and Vmax from ∼6.8- and ∼20.2-fold lower than that of dilute solutions. Interestingly, the effects on Cyt C seem to be more complicated, and crowding exerts a positive effect by increasing Km ∼ 3.6-fold and Vmax ∼ 1.5-fold higher than that of dilute solutions; however, confinement exhibits a negative effect by decreasing Km ∼2.0 and Vmax ∼8.3 times. Additionally, in contrast to traditional nanoparticle-based confinement models, we synthesized a biodegradable nanoparticle to mimic the confined space, and the biggest advantage of this novel model is that the particles can be degraded and thus it can provide more intuitive observations of the properties of the target proteins under confinement and after release. Furthermore, we also evaluated protein activity in different cellular environments, indicating that the exogenous protein activity was closely related to the crowdedness of cellular environments, and the inhibition of protein activity in MDA-MB-231 cancer cells was more obvious than in HEK293 normal cells. Finally, SAXS analysis revealed the correlation between the protein conformation and the different environments. Our work will provide a unique method for precisely assessing whether the target cellular environments are native matrix in which specific exogenous protein drugs are delivered to function or whether they display a therapeutic role, which is of great significance for screening and development of new drugs.

Flexible Seven-in-One Microsensor Embedded in High-Pressure Proton Exchange Membrane Water Electrolyzer for Real-Time Microscopic Monitoring.

The voltage, current, temperature, humidity, pressure, flow, and hydrogen in the high-pressure proton exchange membrane water electrolyzer (PEMWE) can influence its performance and life. For example, if the temperature is too low to reach the working temperature of the membrane electrode assembly (MEA), the performance of the high-pressure PEMWE cannot be enhanced. However, if the temperature is too high, the MEA may be damaged. In this study, the micro-electro-mechanical systems (MEMS) technology was used to innovate and develop a high-pressure-resistant flexible seven-in-one (voltage, current, temperature, humidity, pressure, flow, and hydrogen) microsensor. It was embedded in the upstream, midstream, and downstream of the anode and cathode of the high-pressure PEMWE and the MEA for the real-time microscopic monitoring of internal data. The aging or damage of the high-pressure PEMWE was observed through the changes in the voltage, current, humidity, and flow data. The over-etching phenomenon was likely to occur when this research team used wet etching to make microsensors. The back-end circuit integration was unlikely to be normalized. Therefore, this study used lift-off process to further stabilize the quality of the microsensor. In addition, the PEMWE is more prone to aging and damage under high pressure, so its material selection is very important.

Long-Acting Real-Time Microscopic Monitoring Inside the Proton Exchange Membrane Water Electrolyzer.

The proton exchange membrane water electrolyzer (PEMWE) requires a high operating voltage for hydrogen production to accelerate the decomposition of hydrogen molecules so that the PEMWE ages or fails. According to the prior findings of this R&D team, temperature and voltage can influence the performance or aging of PEMWE. As the PEMWE ages inside, the nonuniform flow distribution results in large temperature differences, current density drops, and runner plate corrosion. The mechanical stress and thermal stress resulting from pressure distribution nonuniformity will induce the local aging or failure of PEMWE. The authors of this study used gold etchant for etching, and acetone was used for the lift-off part. The wet etching method has the risk of over-etching, and the cost of the etching solution is also higher than that of acetone. Therefore, the authors of this experiment adopted a lift-off process. Using the flexible seven-in-one (voltage, current, temperature, humidity, flow, pressure, oxygen) microsensor developed by our team, after optimized design, fabrication, and reliability testing, it was embedded in PEMWE for 200 h. The results of our accelerated aging test prove that these physical factors affect the aging of PEMWE.

The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.

Current Progress of COPD Early Detection: Key Points and Novel Strategies.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, with approximately 70% to 80% of adults with COPD being undiagnosed. Patients with undiagnosed COPD are at increased risk of poor outcomes and a worsened quality of life, making early detection a crucial strategy to mitigate the impact of COPD and reduce the burden on healthcare systems. In the past decade, increased interest has been focused on the development of effective strategies and instrument for COPD early detection. However, identifying undiagnosed cases of COPD is still challenging. Both screening and case-finding approaches have been adopted to identify undiagnosed COPD, with case-finding being recommended by the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and the updated United States Preventive Services Task Force (USPTF) recommendation. Nonetheless, the approaches, criteria, and instruments used for early detection of COPD are varied. However, advances in the taxonomy and risk factors of COPD are continuously being investigated. It is important to continuously assess the current state of knowledge on COPD early detection, given the challenges associated with identifying undiagnosed COPD. This review aims to highlight recent advances in early detection of COPD. To discuss the current challenge and opportunity in COPD early detection, providing an overview of existing literature on COPD case-finding strategies, including the approaches, criteria for subjects, and instruments. The review also summarizes the current progress in COPD case-findings and proposes a COPD case-finding flowchart as an efficient method for identifying at risk COPD patients.

A Flexible 8-in-1 Microsensor Embedded in Proton Battery Stack for Real-Time Microscopic Measurements.

According to the latest literature, it is difficult to measure the multiple important physical parameters inside a proton battery stack accurately and simultaneously. The present bottleneck is external or single measurements, and the multiple important physical parameters (oxygen, clamping pressure, hydrogen, voltage, current, temperature, flow, and humidity) are interrelated, and have a significant impact on the performance, life, and safety of the proton battery stack. Therefore, this study used micro-electro-mechanical systems (MEMS) technology to develop a micro oxygen sensor and a micro clamping pressure sensor, which were integrated into the 6-in-1 microsensor developed by this research team. In order to improve the output and operability of microsensors, an incremental mask was redesigned to integrate the back end of the microsensor in combination with a flexible printed circuit. Consequently, a flexible 8-in-1 (oxygen, clamping pressure, hydrogen, voltage, current, temperature, flow, and humidity) microsensor was developed and embedded in a proton battery stack for real-time microscopic measurement. Multiple micro-electro-mechanical systems technologies were used many times in the process of developing the flexible 8-in-1 microsensor in this study, including physical vapor deposition (PVD), lithography, lift-off, and wet etching. The substrate was a 50 µm-thick polyimide (PI) film, characterized by good tensile strength, high temperature resistance, and chemical resistance. The microsensor electrode used Au as the main electrode and Ti as the adhesion layer.

Umbelliferone and eriodictyol suppress the cellular entry of SARS-CoV-2.

BACKGROUND: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. RESULTS: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. CONCLUSIONS: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.

A Flexible Six-in-One Microsensor Embedded in a Vanadium Redox Flow Battery for Long-Term Monitoring.

The vanadium redox flow battery (VRFB) can be used as a supporting technology for energy storage corresponding to wind and solar power generation. An aqueous vanadium compound solution can be used repeatedly. As the monomer is large, the flow uniformity of electrolytes in the battery is better, the service life is long, and the safety is better. Hence, large-scale electrical energy storage can be achieved. The instability and discontinuity of renewable energy can then be solved. If the VRFB precipitates in the channel, there will be a strong impact on the flow of vanadium electrolyte, and the channel could even be blocked as a result. The factors which influence its performance and life include electrical conductivity, voltage, current, temperature, electrolyte flow, and channel pressure. This study used micro-electro-mechanical systems (MEMS) technology to develop a flexible six-in-one microsensor which can be embedded in the VRFB for microscopic monitoring. The microsensor can perform real-time and simultaneous long-term monitoring of the physical parameters of VRFB, such as electrical conductivity, temperature, voltage, current, flow, and pressure to keep the VRFB system in the best operating condition.

The Antimicrobial Effects of Colistin Encapsulated in Chelating Complex Micelles for the Treatment of Multi-Drug-Resistant Gram-Negative Bacteria: A Pharmacokinetic Study.

Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of 'free' colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.

An Internal Real-Time Microscopic Diagnosis of a Proton Battery Stack during Charging and Discharging.

The proton battery has facilitated a new research direction for technologies related to fuel cells and energy storage. Our R&D team has developed a prototype of a proton battery stack, but there are still problems to be solved, such as leakage and unstable power generation. Moreover, it is unlikely that the multiple important physical parameters inside the proton battery stack can be measured accurately and simultaneously. At present, external or single measurements represent the bottleneck, yet the multiple important physical parameters (oxygen, hydrogen, voltage, current, temperature, flow, and humidity) are interrelated and have a significant impact on the performance, life, and safety of the proton battery stack. This research uses micro-electro-mechanical systems (MEMS) technology to develop a micro oxygen sensor and integrates the six-in-one microsensor that our R&D team previously developed in order to improve sensor output and facilitate overall operation by redesigning the incremental mask and having this co-operate with a flexible board for sensor back-end integration, completing the development of a flexible seven-in-one (oxygen, hydrogen, voltage, current, temperature, flow, and humidity) microsensor.

Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.

Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.