VISTA is an acidic pH-selective ligand for PSGL-1.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer1,2. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies3. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement.

A cross-sectional study: a breathomics based pulmonary tuberculosis detection method.

BACKGROUND: Diagnostics for pulmonary tuberculosis (PTB) are usually inaccurate, expensive, or complicated. The breathomics-based method may be an attractive option for fast and noninvasive PTB detection. METHOD: Exhaled breath samples were collected from 518 PTB patients and 887 controls and tested on the real-time high-pressure photon ionization time-of-flight mass spectrometer. Machine learning algorithms were employed for breathomics analysis and PTB detection mode, whose performance was evaluated in 430 blinded clinical patients. RESULTS: The breathomics-based PTB detection model achieved an accuracy of 92.6%, a sensitivity of 91.7%, a specificity of 93.0%, and an AUC of 0.975 in the blinded test set (n = 430). Age, sex, and anti-tuberculosis treatment does not significantly impact PTB detection performance. In distinguishing PTB from other pulmonary diseases (n = 182), the VOC modes also achieve good performance with an accuracy of 91.2%, a sensitivity of 91.7%, a specificity of 88.0%, and an AUC of 0.961. CONCLUSIONS: The simple and noninvasive breathomics-based PTB detection method was demonstrated with high sensitivity and specificity, potentially valuable for clinical PTB screening and diagnosis.

Transparent nanopaper for ultrashort pulse generation in the near-infrared region.

Transparent nanopaper (T-paper) can be applied in the field of electromagnetic shielding materials, antistatic materials, composite conductive materials, electric pool materials, super capacitors, and thermal management systems. However, this kind of T-paper has not been employed in ultrafast photonics yet. For the first time, to our knowledge, transparent electrical nanopaper is used in fiber lasers, different from the conventional pulsed fiber laser, which operates in the Q-switched regime under low pump power and then in the mode-locked regime under high pump power. Mode-locking is achieved first with a pulse duration of 550 fs under low pump power (166 mW). When further increasing the pump power up to 198 mW, the proposed fiber laser can be converted from a mode-locked to Q-switched state, which is a result of the two-photon absorption effect. The proposed fiber laser based on T-paper can be potentially applied in optical tomography, metrology, spectroscopy, micro-machining technology, and biomedical diagnostics.

A Meta-Analysis on the Association between Tea Consumption and the Risk of Osteoporotic Fractures.

Background: Bone fractures are a significant cause of health impairment. However, observational studies have yielded inconsistent conclusions regarding the correlation between tea consumption and bone fractures. Objective: This meta-analysis aims to examine the influence of tea consumption on bone fractures by conducting a comprehensive search of databases such as PubMed, Embase, and others. Methods: The meta-analysis utilized STATA software and identified a total of 9 observational studies involving 147 950 participants. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using a random effects model. Conclusions: The findings indicate that tea consumption does not exhibit a significant association with the risk of bone fractures. However, further studies with larger sample sizes are warranted to confirm this conclusion.

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72.

BACKGROUND: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored. RESULTS: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage. CONCLUSION: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.

A detection model for cognitive dysfunction based on volatile organic compounds from a large Chinese community cohort.

INTRODUCTION: We explored whether volatile organic compound (VOC) detection can serve as a screening tool to distinguish cognitive dysfunction (CD) from cognitively normal (CN) individuals. METHODS: The cognitive function of 1467 participants was assessed and their VOCs were detected. Six machine learning algorithms were conducted and the performance was determined. The plasma neurofilament light chain (NfL) was measured. RESULTS: Distinguished VOC patterns existed between CD and CN groups. The CD detection model showed good accuracy with an area under the receiver-operating characteristic curve (AUC) of 0.876. In addition, we found that 10 VOC ions showed significant differences between CD and CN individuals (p < 0.05); three VOCs were significantly related to plasma NfL (p < 0.005). Moreover, a combination of VOCs with NfL showed the best discriminating power (AUC = 0.877). DISCUSSION: Detection of VOCs from exhaled breath samples has the potential to provide a novel solution for the dilemma of CD screening.

Computer-aided directed evolution ofl-threonine aldolase for asymmetric biocatalytic synthesis of a chloramphenicol intermediate.

l-Threonine aldolases (LTAs) employing pyridoxal phosphate (PLP) as cofactor can convert low-cost achiral substrates glycine and aldehyde directly into valuable ß-hydroxy-α-amino acids such as (2R,3S)-2-amino-3-hydroxy-3-(4-nitrophenyl) propanoic acid ((R,S)-AHNPA), which is utilized broadly as crucial chiral intermediates for bioactive compounds. However, LTAs' stereospecificity towards the ß carbon is rather moderate and their activity and stability at high substrate load is low, which limits their industrial application. Here, computer-aided directed evolution was applied to improve overall activity, selectivity and stability under desired process conditions of a l-threonine aldolase in the asymmetric synthesis of (R,S)-AHNPA. Selectivity and stability determining regions were computationally identified for structure-guided directed evolution of LTA-variants under efficient biocatalytic process conditions using 40% ethanol as cosolvent. We applied molecular modeling to rationalize selectivity improvement and design focused libraries targeting the substrate binding pocket, and we also used MD simulations in nonaqueous process environment as an effective and promising method to predict potential unstable loop regions near the tetramer interface which are hot-spots for cosolvent resistance. An excellent LTA variant EM-ALDO031 with 18 mutations was obtained, which showed âˆ¼ 30-fold stability improvement in 40% ethanol and diastereoselectivity (de) raised from 31.5% to 85% through a three-phase evolution campaign. Our fast and efficient data-driven methodology utilizing a combination of experimental and computational tools enabled us to evolve an aldolase variant to achieve the target of 90% conversion at up to 150 g/L substrate load in 40% ethanol, enabling the biocatalytic production of ß-hydroxy-α-amino acids from cheap achiral precursors at multi-ton scale.

Toxicity in Takifugu rubripes exposed to acute ammonia: Effects on immune responses, brain neurotransmitter levels, and thyroid endocrine hormones.

Exposure to ammonia can cause convulsions, coma, and death. In this study, we investigate the effects of ammonia exposure on immunoregulatory and neuroendocrine changes in Takifugu rubripes. Fish were sampled at 0, 12, 24, 48, and 96 h following exposure to different ammonia concentrations (0, 5, 50, 100, and 150 mg/L). Our results showed that exposure to ammonia significantly reduced the concentrations of C3, C4, IgM, and LZM whereas the heat shock protein 70 and 90 levels significantly increased. In addition, the transcription levels of Mn-SOD, CAT, GRx, and GR in the liver were significantly upregulated following exposure to low ammonia concertation, however, downregulated with increased exposure time. These findings suggest that ammonia poisoning causes oxidative damage and suppresses plasma immunity. Ammonia exposure also resulted in the elevation and depletion of the T3 and T4 levels, respectively. Furthermore, ammonia stress induced an increase in the corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol levels, and a decrease in dopamine, noradrenaline, and 5-hydroxytryptamine levels in the brain, illustrating that ammonia poisoning can disrupt the endocrine and neurotransmitter systems. Our results provide insights into the mechanisms underlying the neurotoxic effects of ammonia exposure, which helps to assess the ecological and environmental health risks of this contaminant in marine fish.

Decreased expression of HADH is related to poor prognosis and immune infiltration in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the subtype pf kidney cancer having the highest mortality as well as the highest potential of invasion and metastasis. The expression of HADH, encoding a key enzyme in fatty acid ß-oxidation, has rarely been reported to correlate with prognosis and immune infiltration in cancers. This study aimed to explore the prognostic value of HADH in patients with KIRC. Gene expression profiles and clinical data of KIRC patients were acquired from The Cancer Genome Atlas. We compared the expression of HADH between KIRC tissues and normal tissues. Then, the relationship between HADH expression and the clinicopathological characteristics (survival, age, gender, stage, and grade) of KIRC was explored. Data from several online databases and paraffin-embedded specimens from two cohorts were used for external validation (10 cases from Meizhou People's Hospital and another 75 cases from a tissue chip, with both cohorts including KIRC samples and paired normal tissues). We also predicted the fractions of tumor-infiltrating immune cells (TIICs) in various tissues using CIBERSORT. Next, we estimated the prognostic value of differences in TIIC proportions between the high and low HADH expression groups. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms by which HADH expression influences patient survival. The expression of HADH was significantly lower in KIRC tissue than in normal tissue. Decreased expression of HADH was significantly correlated with high histologic grade, advanced stage, and poor prognosis. The differential expression of HADH was validated at the protein level by immunohistochemistry. Multivariate Cox regression analysis indicated that HADH was an independent prognostic factor for KIRC. In addition, HADH expression was significantly associated with the accumulation of several TIICs, especially regulatory T cells. Finally, GSEA revealed that the transcriptome of the low HADH expression group was significantly enriched in genes involved in not only epithelial-mesenchymal transition and inflammatory response but also TNF-α, IL-6-JAK-STAT3, and interferon-γ signaling. In conclusion, our study demonstrated that decreased expression of HADH is related to poor prognosis and immune infiltration in KIRC; this finding may provide crucial information for the development of immunotherapies.

A review of in situ phytoextraction of rare earth elements from contaminated soils.

Rare earth elements (REE), with their distinct physical and chemical properties, are critical components of green economic development. Intensive exploitation and application of REE are wreaking havoc on the environment. But research on REE is still limited to a small number and in a few countries. With the growing interest of REE in modern technologies and their potential ecological risks, phytoextraction seems promising for both REE pollution reduction and resource circulation. This paper summarizes the recent findings in the literature concerning REE hyperaccumulating plants and relevant accumulation mechanisms. Additional interests should be focused on a broader range of plant species and a global scale to achieve a sustainable REE supply.Novelty statementThis paper summarized the referenced potential rare earth elements (REE) hyperaccumulator plants that accumulated higher than REE 100 µg/g and discussed their accumulation and translocation mechanisms.We addressed the synonyms of Dicranopteris pedata, Dicranopteris dichotoma Bernh., and Dicranopteris linearis.Although Dicranopteris pedata has been extensively studied in the sense of REE hyperaccumulation, active phytoextraction outside of its native range, as well as in accumulation of the precious heavy rare earth elements, may be difficult. Thus, further interests should take these disadvantages into account.

High-Precision Cavity Length Demodulation Method for Fiber-Optic Fabry-Perot Sensors Based on Dual Superluminescent Diodes.

A high-precision cross-correlation cavity length demodulation method for fiber-optic Fabry-Perot (F-P) sensors based on two different wavelength superluminescent diodes (SLDs) was proposed. This method can solve the problem of low demodulation accuracy caused by the difficulty in identifying the maximum cross-correlation coefficient when the cavity length of the fiber-optic F-P fiber sensor is too short, or when the spectral bandwidth of the illuminating single-light source is too narrow. This demodulation method is based on the principle that the two main peaks of the two cross-correlation curves corresponding to two different spectral ranges should match, and the average value of the two calculated cavity lengths corresponding to the two matched peaks is determined as the real cavity length. The cavity length demodulation of fiber-optic F-P sensors in the range of 20-200 µm shows a maximum measurement deviation of 0.008 µm, which is significantly smaller than the demodulation result obtained with a single light source, and the standard deviation of the measurement results is only approximately 0.0005 µm, indicating the high precision and stability of a dual SLD cross-correlation demodulation method.

Transcriptomic Analysis Revealed Antimicrobial Mechanisms of Lactobacillus rhamnosus SCB0119 against Escherichia coli and Staphylococcus aureus.

Lactic acid bacteria were reported as a promising alternative to antibiotics against pathogens. Among them, Lactobacillus rhamnosus could be used as probiotics and inhibit several pathogens, but its antibacterial mechanisms are still less known. Here, L. rhamnosus SCB0119 isolated from fermented pickles could inhibit bacterial growth or even cause cell death in Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538, which was mainly attributed to the cell-free culture supernatant (CFS). Moreover, CFS induced the accumulation of reactive oxygen species and destroyed the structure of the cell wall and membrane, including the deformation in cell shape and cell wall, the impairment of the integrity of the cell wall and inner membrane, and the increases in outer membrane permeability, the membrane potential, and pH gradient in E. coli and S. aureus. Furthermore, the transcriptomic analysis demonstrated that CFS altered the transcripts of several genes involved in fatty acid degradation, ion transport, and the biosynthesis of amino acids in E. coli, and fatty acid degradation, protein synthesis, DNA replication, and ATP hydrolysis in S. aureus, which are important for bacterial survival and growth. In conclusion, L. rhamnosus SCB0119 and its CFS could be used as a biocontrol agent against E. coli and S. aureus.

Effect of winter feeding frequency on growth performance, biochemical blood parameters, oxidative stress, and appetite-related genes in Takifugu rubripes.

Tiger pufferfish (Takifugu rubripes) is one of Asia's most economically valuable aquaculture species. However, winter production of this species in North China is limited by low water temperature and unavailability of high-quality feed, resulting in high mortality and low profitability. Therefore, the aim of this study was to evaluate the effect of feeding frequency (F1: one daily meal; F2: two daily meals; F3: four daily meals; F4: continuous diurnal feeding using a belt feeder) on the growth performance, plasma biochemistry, digestive and antioxidant enzyme activities, and expression of appetite-related genes in T. rubripes (initial weight: 266.80 ± 12.32 g) cultured during winter (18.0 ± 1.0 °C) for 60 days. The results showed that fish in the F3 group had the highest final weight, weight gain rate, specific growth rate, survival rate, and best feed conversion ratio. Additionally, daily feed intake increased significantly with increasing feeding frequency. The protein efficiency and lipid efficiency ratios of fish in the F3 group were significantly higher than those of fish in the other groups. Furthermore, total cholesterol, triglycerides, and glucose levels increased with increasing feeding frequency, peaking in the F2 group and decreasing under higher feeding frequencies. The antioxidant (superoxide dismutase, catalase, glutathione, and glutathione peroxidase) and digestive (trypsin, amylase, and lipase) enzyme activities of fish in the F1 group were significantly higher than those of fish in the F3 and F4 groups. Additionally, there was a decrease in orexin expression with increasing feeding frequency. In contrast, the expression levels of tachykinin, cholecystokinin, and leptin increased with increasing feeding frequency, peaking in the F4 group. Overall, the findings of this study indicated that a feeding frequency of four meals per day was optimal for improved growth performance of pufferfish juveniles cultured during winter.

High-Throughput Surface Plasmon Resonance Biosensors for Identifying Diverse Therapeutic Monoclonal Antibodies.

Identification of antibodies targeting diverse functional epitopes on an antigen is highly crucial for discovering effective therapeutic candidates. Employing a traditional stepwise antibody "screening funnel" as well as prioritizing affinity-based selections over epitope-based selections, result in lead antibody panels lacking epitope diversity. In the present study, we employed an array-based surface plasmon resonance (SPR) platform to perform high-throughput epitope binning analysis on a large number of monoclonal antibodies (mAbs) generated in the early drug discovery process. The mAb panel contained clones from different antibody generation techniques and diverse transgenic mouse strains. The epitope binning results were analyzed in unique ways using various visualizations in the form of dendrograms and network plots, which assisted in determining diversity and redundancy in the mAb sample set. The binning data were further integrated with affinity information to evaluate the performance of seven different transgenic mouse strains. The combination of epitope binning results with binding kinetics and sequence analysis provided an effective and efficient way of selecting high affinity antibodies representing a diverse set of sequence families and epitopes.

Negative correlation between endoglin levels and coronary atherosclerosis.

BACKGROUND: Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. METHODS: We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data. RESULTS: Research has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells. CONCLUSION: The endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.

Fiber-optic vector magnetic field sensor based on a magnetic-fluid-infiltrated large-core-offset Mach-Zehnder interferometer.

A fiber-optic vector magnetic field sensor based on a large-core-offset Mach-Zehnder interferometer (MZI) infiltrated by magnetic fluid (MF) is proposed and demonstrated in this paper. By large-core-offset fusion splicing of a short single-mode fiber (SMF) between a lead-in SMF and a coupling multi-mode fiber, the MZI with a sub-millimeter length is formed, which is then sealed in an MF-infiltrated glass capillary. Through the MF's refractive index modulation by external magnetic field, the phase of the light passing through the MZI is altered. As a result, the transmission spectrum can be monitored for the magnetic field measurement. Furthermore, from the axial-asymmetry of the large-core-offset MZI structure, the proposed sensor possesses vectorial magnetic-field-sensing ability. Experiments show that the MF-infiltrated large-core-offset MZI vector magnetic-field sensor can achieve a high wavelength sensitivity of 96.68 pm/Oe in a magnetic field range of 50-130 Oe.

HE4 overexpression decreases pancreatic cancer Capan-1 cell sensitivity to paclitaxel via cell cycle regulation.

BACKGROUND: Paclitaxel is a first-line chemotherapy drug for pancreatic, ovarian, endometrial cancers and other malignancies. However, its efficacy is often compromised by decreased cell sensitivity or the development of resistance. Human epididymis protein 4 (HE4) is highly expressed in gynecologic and pancreatic cancer tissues, and its serum levels are used for patient triage and assistant diagnosis of gynecologic cancers. Previous studies have shown that HE4 overexpression could promote cancer cell proliferation and the growth of tumor xenografts, which suggests its potential involvement in cancer chemosensitivity. METHODS: Two pancreatic cancer cell lines, Capan-1 and Suit-2, were transiently transfected with an HE4 overexpression plasmid, and transfected cells were treated with paclitaxel. S-phase cells were labeled using BrdU, and cell positivity rates were determined by counting BrdU-positive cells. Following HE4 overexpression and/or drug treatment, a western blotting analysis was performed to determine the protein alterations of PCNA and p21, two important cell cycle regulators. RESULTS: HE4 overexpression not only promoted the proliferation of the Capan-1 pancreatic cells, but also significantly decreased cell sensitivity to paclitaxel. Results from western blotting showed that paclitaxel inhibited cell proliferation by decreasing the expression of PCNA and increasing the expression of p21. Data analysis indicated interactive actions between HE4 function and paclitaxel effects, both converging to cell cycle regulation. CONCLUSION: These findings suggest that HE4 could be a potential therapeutic target for the sensitization of pancreatic cancer cells to paclitaxel treatment. HE4 expression levels may be used to predict the sensitivity of pancreatic cancer patients to paclitaxel.

Investigation of the differences between the medical personnel's and general population's view on the doctor-patient relationship in China by a cross-sectional survey.

BACKGROUND: Due to economic development and an increase in the aging population, the demand for medical resources is increasing. A good doctor-patient relationship (DPR) can optimize patients' medical experience and improve treatment efficiency. The DPR, however, is currently in crisis in China. To explore ways to improve DPR, this study assessed the views on the status of the DPR, medical services, and the general situation of medical work among medical personnel (MP) and the general population (GP). METHODS: This cross-sectional study, conducted between December 2019 and March 2020, targeted the MP and the GP in Nanjing City, Jiangsu Province, and Zhengzhou City, Henan Province. A total of 154 MP and 329 GP answered a self-administered questionnaire through Questionnaire Star and WeChat apps. Wilcoxon's Sign Rank Test, Chi-square test, and frequency distributions and percentages were used to process the data. RESULTS: Only 11.04% of the MP and 14.89% of the GP believed that the current DPR was harmonious. Moreover, 54.55% of the MP and 71.12% of the GP believed that the medical industry was a service industry. While 14.29% of the MP and 64.44% of the GP thought medical staff earned high salaries, 19.48% of the MP and 47.11% of the GP wanted their children to be in the medical industry. The recognition of the current status of the DPR did not affect the GP's preference for their children's practice (p < 0.05). Most MPs hoped to improve salaries (40.26%), followed by safety (17.53%) and social status (12.99%); only 8.44% of the MP wanted to improve the DPR. CONCLUSION: The MP's and GP's views on the current status of DPR, the importance of medical service attitudes, and the general sense of the medical industry were similar. However, there was a significant difference in the perception of the nature of medical services and the income of the people employed in the medical industry between the two groups. Balancing the expectations of patients in the medical industry and increasing public awareness of the actual situation in the medical industry may be a feasible way to improve the DPR.

Squared peak-to-peak algorithm for the spectral interrogation of short-cavity fiber-optic Fabry-Perot sensors.

The cavity length of short-cavity Fabry-Perot (FP) sensors cannot be effectively interrogated using the conventional peak-to-peak method if the spectrum of the exciting source is not wide enough. In this paper, we propose a squared peak-to-peak algorithm for interrogation of short-cavity fiber-optic FP sensors. By squaring the DC-filtered reflection spectrum of an FP sensor in the frequency domain, we produce an additional peak, with which the cavity length of a sensor can be estimated using the same calculations as performed with the conventional peak-to-peak method. For investigation of the feasibility of this technique, we conducted simulations and practical experiments analyzing fiber-optic FP sensors with cavity lengths in the range of 15-25 µm. The maximum error in cavity length estimated using the proposed algorithm in experiments was 0.030 µm.

An efficient Screening System in Yeast to Select a Hyperactive piggyBac Transposase for Mammalian Applications.

As non-viral transgenic vectors, the piggyBac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. However, further improvements in transpose activity are required for industrialization and clinical applications. Herein, we established a one-plasmid effective screening system and a two-step high-throughput screening process in yeast to isolate hyperactive mutants for mammalian cell applications. By applying this screening system, 15 hyperactive piggyBac transposases that exhibited higher transpose activity compared with optimized hyPBase in yeast and four mutants that showed higher transpose activity in mammalian cells were selected among 3000 hyPBase mutants. The most hyperactive transposase, bz-hyPBase, with four mutation sites showed an ability to yield high-efficiency editing in Chinese hamster ovarian carcinoma (CHO) cells and T cells, indicating that they could be expanded for gene therapy approaches. Finally, we tested the potential of this screening system in other versions of piggyBac transposase.