TFEB activator tanshinone IIA and derivatives derived from Salvia miltiorrhiza Bge. Attenuate hepatic steatosis and insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. (SMB) is an herbal medicine extensively used for improving metabolic disorders, including Nonalcoholic fatty liver disease (NAFLD). However, the potential material basis and working mechanism still remained to be elucidated. AIM OF THE STUDY: To find potential ingredients for therapy of NAFLD by high content screening and further verify the efficacy on restoring hepatic steatosis and insulin resistance, and clarify the potential working mechanism. MATERIALS AND METHODS: The mouse transcription factor EB (Tfeb) in preadipocytes was knocked out by CRISPR-Cas9 gene editing. High content screening of TFEB nuclear translocation was performed to identify TFEB activators. The effect of candidate compounds on reducing lipid accumulation was evaluated using Caenorhabditis elegans (C. elegans). Then the role of Salvia miltiorrhiza extract (SMB) containing Tanshinone IIA and the derivatives were further investigated on high-fat diet (HFD) fed mice. RNA-seq was performed to explore potential molecular mechanism of SMB. Finally, the gut microbiota diversity was evaluated using 16S rRNA sequencing to investigate the protective role of SMB on regulating gut microbiota homeostasis. RESULTS: Knockout of Tfeb led to excessive lipid accumulation in adipocytes while expression of TFEB homolog HLH-30 in C. elegans (MAH240) attenuated lipid deposition. Screening of TFEB activators identified multiple candidates from Salvia miltiorrhiza, all of them markedly induced lysosome biogenesis in HepG2 cells. One of the candidate compounds Tanshinone IIA significantly decreased lipid droplet deposition in HFD fed C. elegans. Administration of SMB on C57BL/6J mice via gastric irrigation at the dose of 15 g/kg/d markedly alleviated hepatic steatosis, restored serum lipid profile, and glucose tolerance. RNA-seq showed that gene expression profile was altered and the genes related to lipid metabolism were restored. The disordered microbiome was remodeled by SMB, Firmicutes and Actinobacteriotawere notably reduced, Bacteroidota and Verrucomicrobiota were significantly increased. CONCLUSION: Taken together, the observations presented here help address the question concerning what were the main active ingredients in SMB for alleviating NAFLD, and established that targeting TFEB was key molecular basis for the efficacy of SMB.

Mechanism analysis of essential oil from Radix Bupleuri for the treatment of asthma through regulation of ectopic olfactory receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri is the root of Bupleurum chinense DC. (BC) and a classic aromatic traditional Chinese medicine. The traditional pharmacological effects of Radix Bupleuri are alleviating bronchial spasms, dilating airways, and promoting the resolution of respiratory inflammation, thereby reducing asthma symptoms. AIM OF THE STUDY: Studies have demonstrated the efficacy of water extracts from BC in asthma treatment. However, the potential role of volatile oil, another active constituent in BC, remains unexplored with asthma. Notably, volatile oil is renowned for its ease of absorption and direct targeting of affected areas, offering distinct advantages in alleviating airway inflammation. This study aims to explain the anti-asthmatic mechanism of BC-oil through in vivo and in vitro pharmacological experiments. MATERIALS AND METHODS: Firstly, the OVA-induced SD rat asthma model was utilized to evaluate the pharmacological effect of BC-oil by lung function monitoring, HE staining, flow cytometry, ELISA, and RT-qPCR. The anti-asthmatic mechanism was further analyzed by combining transcriptomic analysis of lung tissue from rat model and airway smooth muscle tissue from public database. Initially, GC-MS was used to analyze the components of BC-oil. The anti-asthmatic activity was evaluated in 16-HBE, RBL-2H3, and ASMC cells using CAMKII inhibitors to explore of the critical signal transduction regulated by BC-oil. Furthermore, molecular docking and calcium flow assay were utilized to screen and identify the active components from BC-oil. RESULTS: Oral administration of BC-oil significantly enhanced pulmonary function in asthmatic SD rats by reducing airway resistance and elastic resistance. Additionally, BC-oil inhibited inflammatory cytokines, including serum IL-2, pulmonary Il1b, Tnf, and Cxcl13, demonstrating potent anti-inflammatory and immunomodulatory effects. In this study, we analyzed the significant role of OR2W3 in asthma using public transcriptomic data. Furthermore, we indicated that BC-oil regulated the expression of Olr1433 and GNAL in rat lung tissue. BC-oil reduced degranulation and inhibited gene expression of Il3 and Tnf in RBL-2H3 cells and suppressed gene expression of IL8 and TNF in 16-HBE cells. BC-oil also attenuated airway smooth muscle cell proliferation and expression of Acta2 and Ccnd1. Furthermore, BC-oil regulates asthma-related cellular processes by activating CAMKII. GC-MS analysis identified 11 components of BC-oil, and n-hexadecanoic acid, linoleic acid and oleic acid from BC-oil were identified to interact with OR2W3 by molecular docking. The calcium flow assay revealed linoleic acid as a significant activator of OR2W3 and indicated that BC-oil alleviated asthma through the ectopic olfactory signaling pathway. CONCLUSIONS: The mechanism of BC-oil in treating asthma through signal transduction of OR2W3 is revealed at the molecular and cellular levels.

One-step time-resolved cascade logic gate microfluidic chip for home testing of SARS-CoV-2 and flu B.

Home testing technology strategy is critical for early screening of disease. However, current home testing technologies often require complex processes, which limits their application. In this study, a time-resolved cascade logic gate microfluidic chip (TCLMC) was revealed to enable capillary force-based one-step operation without manual intervention or professional equipment. By analogy with logic gates in the circuit, TCLMC could automatically control the fluid flow and regulate the incubation time to optimize the immunoassay. The limit of detection of TCLMC for SARS-CoV-2 and influenza B virus (Flu B) was 134.94 and 79.17 pg mL-1 within 10 min. Additionally, this study tested saliva samples from 12 Flu B patients and 24 healthy controls to verify its clinical application. The results showed that TCLMC had high sensitivity (100%), specificity (100%), and accuracy (100%). This study provides a new one-step strategy for home testing and demonstrates its great potential in the diagnosis field.

N-doped porous carbon with ZIF-67-derived CoFe2O4-Fe particles for supercapacitors.

The development of novel materials for electrodes with high energy densities is essential to the advancement of energy storage technologies. In this study, N-doped layered porous carbon with ZIF-67-derived binary CoFe2O4-Fe particles was successfully fabricated by the pyrolysis of an Fe-based chitosan (CS) hydrogel mixed with ZIF-67 particles. Various characterization techniques were employed to assess the performance of the prepared porous CoFe2O4-Fe@NC composite. This composite exhibits excellent performance owing to the effective combination of multivalent CoFe2O4-Fe particles derived from ZIF-67 with N-doped porous carbon substances with a high surface area, which helps to accelerate ion and charge transfer. The specific capacitance of the CoFe2O4-Fe@NC composite carbonized at 700 °C reached 3960.9F/g at 1 A/g. When this composite is combined with activated carbon (AC) to construct an asymmetric supercapacitor (ASC), a density of energy of up to 84.9 W h kg-1 is attained at a power capacity of 291.6 W kg-1. Moreover, this composite maintained a capacitance retention of up to 94.9 % after 10,000 cycles. This work offers new perspectives on high-performance supercapacitors and their applications.

Advancing Microfluidic Immunity Testing Systems: New Trends for Microbial Pathogen Detection.

Pathogenic microorganisms play a crucial role in the global disease burden due to their ability to cause various diseases and spread through multiple transmission routes. Immunity tests identify antigens related to these pathogens, thereby confirming past infections and monitoring the host's immune response. Traditional pathogen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs), are often labor-intensive, slow, and reliant on sophisticated equipment and skilled personnel, which can be limiting in resource-poor settings. In contrast, the development of microfluidic technologies presents a promising alternative, offering automation, miniaturization, and cost efficiency. These advanced methods are poised to replace traditional assays by streamlining processes and enabling rapid, high-throughput immunity testing for pathogens. This review highlights the latest advancements in microfluidic systems designed for rapid and high-throughput immunity testing, incorporating immunosensors, single molecule arrays (Simoas), a lateral flow assay (LFA), and smartphone integration. It focuses on key pathogenic microorganisms such as SARS-CoV-2, influenza, and the ZIKA virus (ZIKV). Additionally, the review discusses the challenges, commercialization prospects, and future directions to advance microfluidic systems for infectious disease detection.

Advances in Nucleic Acid Assays for Infectious Disease: The Role of Microfluidic Technology.

Within the fields of infectious disease diagnostics, microfluidic-based integrated technology systems have become a vital technology in enhancing the rapidity, accuracy, and portability of pathogen detection. These systems synergize microfluidic techniques with advanced molecular biology methods, including reverse transcription polymerase chain reaction (RT-PCR), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR), have been successfully used to identify a diverse array of pathogens, including COVID-19, Ebola, Zika, and dengue fever. This review outlines the advances in pathogen detection, attributing them to the integration of microfluidic technology with traditional molecular biology methods and smartphone- and paper-based diagnostic assays. The cutting-edge diagnostic technologies are of critical importance for disease prevention and epidemic surveillance. Looking ahead, research is expected to focus on increasing detection sensitivity, streamlining testing processes, reducing costs, and enhancing the capability for remote data sharing. These improvements aim to achieve broader coverage and quicker response mechanisms, thereby constructing a more robust defense for global public health security.

Discovery of LC-MI-3: A Potent and Orally Bioavailable Degrader of Interleukin-1 Receptor-Associated Kinase 4 for the Treatment of Inflammatory Diseases.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target in inflammation-related diseases. However, the inhibition of IRAK4 kinase activity may lead to moderate anti-inflammatory efficacy owing to the dual role of IRAK4 as an active kinase and a scaffolding protein. Herein, we report the design, synthesis, and biological evaluation of an efficient and selective IRAK4 proteolysis-targeting chimeric molecule that eliminates IRAK4 scaffolding functions. The most potent compound, LC-MI-3, effectively degraded cellular IRAK4, with a half-maximal degradation concentration of 47.3 nM. LC-MI-3 effectively inhibited the activation of downstream nuclear factor-κB signaling and exerted more potent pharmacological effects than traditional kinase inhibitors. Furthermore, LC-MI-3 exerted significant therapeutic effects in lipopolysaccharide- and Escherichia coli-induced acute and chronic inflammatory skin models compared with kinase inhibitors in vivo. Therefore, LC-MI-3 is a candidate IRAK4 degrader in alternative targeting strategies and advanced drug development.

Effectiveness of video-based psychiatric rehabilitation for patients with early-phase schizophrenia spectrum: A randomized controlled trial.

AIM: This study aimed to establish a comprehensive set of recovery-oriented rehabilitation programs for individuals with schizophrenia, comparing the efficacy of video-based rehabilitation to traditional face-to-face interventions. The primary objective was to assess whether video-based rehabilitation could serve as a viable alternative for individuals with schizophrenia residing in remote areas. METHODS: A randomized controlled study was used to recruit 80 patients with schizophrenia in a stable post-hospitalization stage following discharge. Participants were categorized into three groups: 24 in the control group, 21 in the face-to-face group, and 35 in the remote group. Assessment parameters included psychiatric symptoms, social skills, family function and self-stigma. RESULTS: A total of 68 participants completed the program. The findings indicated significant differences (p < .05) between the control group and intervention group, particularly in the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance Scale (PSP). CONCLUSIONS: The rehabilitation program, tailored for patients in the early phase of the schizophrenia spectrum, demonstrates both effectiveness and feasibility in enhancing clinical symptoms and social functions. Notably, interventions conducted via video proved to be equally effective as those administered face-to-face.

Integrating Network Pharmacology, Quantitative Metabolic Network Analysis, In Vitro Experiments, and Molecular Dynamics to Explore the Mechanism of Angelica Sinensis for Regulating Bone Metabolism.

BACKGROUND: Bone metabolic diseases are serious health issues worldwide. Angelica sinensis (AS) is traditionally used in Chinese medicine for treating bone metabolism diseases clinically. However, the mechanism of AS in regulating bone metabolism remains uncertain. OBJECTIVE: The current investigation was structured to elucidate the potential mechanisms of AS for modulating bone metabolism. METHODS: Firstly, targets of AS regulating bone metabolism were collected by network pharmacology. Then, the transcriptional regulation of RUNX2 was enriched as one of the key pathways for AS to regulate bone metabolism, constructing its metabolic network. Secondly, combining molecular docking, network efficiency, and network flux analyses, we conducted a quantitative evaluation of the metabolic network to reveal the potential mechanisms and components of AS regulating bone metabolism. Finally, we explored the effect of AS on the differentiation of osteoclasts from M-CSF and RANKL-induced RAW264.7 cells, as well as its impact on the osteogenic induction of MC3T3-E1 cells. We verified the mechanism and key targets of AS on bone metabolism using qRT-PCR. Furthermore, the key component was preliminarily validated through molecular dynamics simulation. RESULTS: Quantitative metabolic network of the transcriptional regulation of RUNX2 was constructed to illustrate the potential mechanism of AS for regulating bone metabolism, indicating that ferulic acid may be a pharmacological component of AS that interferes with bone metabolism. AS suppressed osteoclast differentiation in M-CSF and RANKL-induced RAW264.7 cells and reversed the expressions of osteoclastic differentiation markers, including RUNX2 and SRC. Additionally, AS induced osteogenic generation in MC3T3-E1 cells and reversed the expressions of markers associated with osteoblastic generation, such as RUNX2 and HDAC4. Molecular dynamics simulation displayed a strong binding affinity among ferulic acid, HDAC4 and SRC. CONCLUSION: This study reveals a systematic perspective on the intervention bone mechanism of AS by transcriptive regulation by RUNX2, guiding the clinical use of AS in treating diseases of the skeletal system.

A root cap-localized NAC transcription factor controls root halotropic response to salt stress in Arabidopsis.

Plants are capable of altering root growth direction to curtail exposure to a saline environment (termed halotropism). The root cap that surrounds root tip meristematic stem cells plays crucial roles in perceiving and responding to environmental stimuli. However, how the root cap mediates root halotropism remains undetermined. Here, we identified a root cap-localized NAC transcription factor, SOMBRERO (SMB), that is required for root halotropism. Its effect on root halotropism is attributable to the establishment of asymmetric auxin distribution in the lateral root cap (LRC) rather than to the alteration of cellular sodium equilibrium or amyloplast statoliths. Furthermore, SMB is essential for basal expression of the auxin influx carrier gene AUX1 in LRC and for auxin redistribution in a spatiotemporally-regulated manner, thereby leading to directional bending of roots away from higher salinity. Our findings uncover an SMB-AUX1-auxin module linking the role of the root cap to the activation of root halotropism.

Development and Characterization of Bio-Based Formaldehyde Free Sucrose-Based Adhesive for Fabrication of Plywood.

In order to solve the problem of excessive consumption of petrochemical resources and the harm of free formaldehyde release to human health, biomass raw materials, such as sucrose (S) and ammonium dihydrogen phosphate (ADP) can be chemically condensed in a simple route under acidic conditions to produce a formaldehyde free wood adhesive (S-ADP), characterized by good storage stability and water resistance, and higher wet shear strength with respect to petroleum based phenolic resin adhesive. The dry and boiling shear strength of the plywood based on S-ADP adhesive are as high as 1.05 MPa and 1.19 MPa, respectively. Moreover, is Modulus of Elasticity (MOE) is as high as 4910 MPa. Interestingly, the plywood based on the developed S-ADP adhesive exhibited good flame retardancy. After burning for 90 s, its shape remains unchanged. Meanwhile, it can be concluded from thermomechanical analysis (TMA) and thermogravimetric analysis (TGA) that the S-ADP acquired excellent modulus of elasticity (MOE) and good thermal stability. It is thus thought promisingly that the use of S-ADP adhesive as a substitute for PF resin adhesive seems feasible in the near future.

The application of autofluorescence system contributes to the preservation of parathyroid function during thyroid surgery.

PURPOSE: The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS: A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS: The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION: This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.

Air-Liquid Interface Microfluidic Monitoring Sensor Platform for Studying Autophagy Regulation after PM2.5 Exposure.

Undoubtedly, a deep understanding of PM2.5-induced tumor metastasis at the molecular level can contribute to improving the therapeutic effects of related diseases. However, the underlying molecular mechanism of fine particle exposure through long noncoding RNA (lncRNA) regulation in autophagy and, ultimately, lung cancer (LC) metastasis remains elusive; on the other hand, the related monitoring sensor platform used to investigate autophagy and cell migration is lacking. Herein, this study performed an air-liquid interface microfluidic monitoring sensor (AIMMS) platform to analyze human bronchial epithelial cells after PM2.5 stimulation. The multiomics analysis [RNA sequencing (RNA-seq) on lncRNA and mRNA expressions separately] showed that MALAT1 was highly expressed in the PM2.5 treatment group. Furthermore, RNA-seq analysis demonstrated that autophagy-related pathways were activated. Notably, the main mRNAs associated with autophagy regulation, including ATG4D, ATG12, ATG7, and ATG3, were upregulated. Inhibition or downregulation of MALAT1 inhibited autophagy via the ATG4D/ATG12/ATG7/ATG3 pathway after PM2.5 exposure and ultimately suppressed LC metastasis. Thus, based on the AIMMS platform, we found that MALAT1 might become a promising therapeutic target. Furthermore, this low-cost AIMMS system as a fluorescence sensor integrated with the cell-monitor module could be employed to study LC migration after PM2.5 exposure. With the fluorescence cell-monitoring module, the platform could be used to observe the migration of LC cells and construct the tumor metastasis model. In the future, several fluorescence probes, including nanoprobes, could be used in the AIMMS platform to investigate many other biological processes, especially cell interaction and migration, in the fields of toxicology and pharmacology.

Construction and Application of a Traditional Chinese Medicine Syndrome Differentiation Model for Dysmenorrhea Based on Machine Learning.

BACKGROUND: Dysmenorrhea is one of the most common ailments affecting young and middle-aged women, significantly impacting their quality of life. Traditional Chinese Medicine (TCM) offers unique advantages in treating dysmenorrhea. However, an accurate diagnosis is essential to ensure correct treatment. This research integrates the age-old wisdom of TCM with modern Machine Learning (ML) techniques to enhance the precision and efficiency of dysmenorrhea syndrome differentiation, a pivotal process in TCM diagnostics and treatment planning. METHODS: A total of 853 effective cases of dysmenorrhea were retrieved from the CNKI database, including patients' syndrome types, symptoms, and features, to establish the TCM information database of dysmenorrhea. Subsequently, 42 critical features were isolated from a potential set of 86 using a selection procedure augmented by Python's Scikit-Learn Library. Various machine learning models were employed, including Logistic Regression, Random Forest Classifier, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Artificial Neural Networks (ANN), each chosen for their potential to unearth complex patterns within the data. RESULTS: Based on accuracy, precision, recall, and F1-score metrics, SVM emerged as the most effective model, showcasing an impressive precision of 98.29% and an accuracy of 98.24%. This model's analytical prowess not only highlighted the critical features pivotal to the syndrome differentiation process but also stands to significantly aid clinicians in formulating personalized treatment strategies by pinpointing nuanced symptoms with high precision. CONCLUSION: The study paves the way for a synergistic approach in TCM diagnostics, merging ancient wisdom with computational acuity, potentially innovating the diagnosis and treatment mode of TCM. Despite the promising outcomes, further research is needed to validate these models in real-world settings and extend this approach to other diseases addressed by TCM.

Discovery of a doublecortin-like kinase 1 inhibitor to prevent inflammatory responses in acute lung injury.

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein kinase involved in neurogenesis and human cancer. Recent studies have revealed a novel functional role for DCLK1 in inflammatory signaling, thus positioning it as a novel target kinase for respiratory inflammatory disease treatment. In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKß phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory activity in an LPS-challenged acute lung injury model. These findings suggest that compound a24 may serve as a novel candidate for the development of DCLK1 inhibitors and a potential therapeutic agent for the treatment of inflammatory diseases.

Developing high performance biodegradable film based on crosslinking of cellulose acetate and tannin using caprolactone.

The use of metal catalysts during the production process of cellulose acetate (CA) film can have an impact on the environment, due to their toxicity. Diphenyl phosphate (DPP) was used instead of toxic metal catalyst to react with cellulose acetate, tannin (T) and caprolactone (CL) for preparation of cellulose acetate-caprolactone-tannin (CA-CL-T) film. The results show that DPP can produce a cross-linked network structure composed of tannin, caprolactone and cellulose acetate. The maximum molecular weight reached 113,260 Da. The introduction of tannin and caprolactone into cellulose acetate caused the resulting CA-CL-T film acquire excellent strengthening/toughening effect, in which a tensile strength of 23 MPa and elongation at break of 18 % were attained. More importantly, the resistance of the film to UV radiation was significantly improved with the tannin addition, which was corroborated by the CA-CL-T film still exhibiting a tensile strength of 13 MPa and elongation at break around 13 % after continuous exposure to UV radiation for 9 days. On the other hand, the insertion of caprolactone provoked enhancement of the overall moisture resistance. Five days treatment of the films with Penicillium sp. induced gradual drop in quality, indicating the CA-CL-T film show response to biodegradation. In all, the effective crosslinking between the components of the developed material is responsible for the acquired set of these distinct characteristics.

Serum sex hormones correlate with pathological features of papillary thyroid cancer.

PURPOSE: Sex hormones are thought to be responsible for the unique gender differences in papillary thyroid cancer(PTC). Most previous studies on these have focused on the expression of estrogen receptors, or have been limited to animal studies. The aim of our study was to explore the relationship between serum sex hormones and the pathological features of PTC in the clinical setting, as further evidence of the role of sex hormones in PTC. METHODS: Retrospective data analysis of patients who underwent thyroid surgery at the Department of Thyroid Surgery, Nanjing Drum Tower Hospital from January 2022 to September 2022 Correlation between serum sex hormone and pathological features was analyzed in male patients and in menopausal female patients. Serum sex hormones include luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), total testosterone(TT), progesterone(P), and prolactin(PRL). Tumor pathological characteristics include the number and size of tumor, presence of extrathyroidal extension(ETE), presence of lymph node metastasis(LNM). RESULTS: Preoperative serum E2 in male patients was positively correlated with tumor size in PTC, LH was negatively correlated with LNM, while TT and P were negatively correlated with ETE. Similar findings were not observed in menopausal female patients. CONCLUSION: We observed that serum sex hormones correlate with the pathological features of PTC in male patients, for the first time in a clinical study. High serum estrogens may be a risk factor for PTC, while androgens are the opposite. This somewhat corroborates previous research and provides new variables for future PTC prediction models.

A low-cost and portable fluorometer based on an optical pick-up unit for chlorophyll-a detection.

Chlorophyll-a (Chl-a) fluorescence detection is an important technique for monitoring water quality. In this work, we proposed an approach that employs the mass-produced low-cost optical pick-up unit (OPU) extracted from the high-definition digital versatile disc (HD-DVD) drive as the key optical component for our chlorophyll-a fluorometer. The built-in blue-violet 405 nm laser diode of the OPU acts as the excitation light to perform laser-induced fluorescence (LIF). The laser driver and a series of intrinsic lenses within the OPU, such as an objective lens with a numerical aperture (NA) of 0.65 and a collimating lens, help reduce the size, cost, and system complexity of the fluorometer. By integrating off-the-shelf electronic components, miniaturized optical setups, and 3D-printed assemblies, we have developed a low-cost, easy-to-make, standalone, and portable fluorometer. Finally, we validated the performance of the device for chlorophyll-a fluorescence detection under laboratory and on-site conditions, which demonstrated its great potential in water monitoring applications. The limit of detection (LOD) for chlorophyll-a is 0.35 µg/L, the size of the device is 151 × 100 × 80 mm3, and the total cost of the proposed fluorometer is as low as 137.5 USD. © 2023 Elsevier Science. All rights reserved.

Expression and Purification of FGFR1-Fc Fusion Protein and Its Effects on Human Lung Squamous Carcinoma.

Molecular-targeted therapies for lung squamous cell carcinoma (LSCC) are limited mainly because targetable oncogenic aberrations are absent in LSCC. Recent genomic analyses have revealed that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in LSCC progression via cancer cell proliferation and angiogenesis. In the present study, we designed, expressed, and purified a fibroblast growth factor receptor fragment (FGFR1-Fc) fusion protein using NS/0 cells. In FGF2-FGFR1 overexpressed NCI-H1703 cells, the FGFR1-Fc fusion protein effectively inhibited proliferation and invasion and arrested the cell cycle at the G0-G1 phase. In NCI-H1703 cells treated with the FGFR1-Fc fusion protein, the phosphorylation levels of FGFR1, FRS2, ERK, and AKT were significantly reduced. Using an siRNA assay, we demonstrated that FGF2-FGFR1 is the major anti-tumor target of FGFR1-Fc fusion the FGFR1-Fc fusion protein, which also significantly inhibited proliferation and invasion by NCI-H1703 cells via the FGF2-FGFR1 signaling pathway. In addition, the FGFR1-Fc fusion protein significantly inhibited angiogenesis in an embryonic chorioallantoic membrane model. The FGFR1-Fc fusion protein may be an effective therapeutic candidate for LSCC.