Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Three-axis angle measurement method based on an optical wedge.

A three-axis angle measurement method is proposed using an optical wedge as a reflector. In this paper, the mathematical model of three-axis angle solving corresponding to the method is derived, and it is verified and corrected by establishing an optical simulation model, and, finally, the feasibility and measurement accuracy of the method are verified by using a principle prototype. The experimental results show that the RMS values of the measurement errors of pitch angle α, yaw angle ß, and roll angle γ are 6.27 ' ' , 4.35 ' ' , and 17.68 ' ' , respectively, within the measurement range of ±2∘, and the measurement accuracy is insensitive to the measurement distance.

Evaluating the Microheterogeneous Distribution of Photochemically Generated Singlet Oxygen Using Furfuryl Amine.

Singlet oxygen (1O2) is an important reactive species in natural waters produced during photolysis of dissolved organic matter (DOM). Prior studies have demonstrated that 1O2 exhibits a microheterogeneous distribution, with [1O2] in the interior of DOM macromolecules ∼30 to 1000-fold greater than in bulk solution. The [1O2] profile for DOM-containing solutions has been determined mainly by the use of hydrophobic probes, which are not commercially available. In this study, we employed a dual-probe method combining the widely used hydrophilic 1O2 probe furfuryl alcohol (FFA) and its structural analogue furfuryl amine (FFAm). FFAm exists mainly as a cation at pH <9 and was therefore hypothesized to have an enhanced local concentration in the near-DOM phase, whereas FFA will be distributed homogeneously. The probe pair was used to quantify apparent [1O2] in DOM samples from different isolation procedures (humic acid, fulvic acid, reverse osmosis) and diverse origins (aquatic and terrestrial) as a function of pH and ionic strength, and all samples studied exhibited enhanced reactivity of FFAm relative to FFA, especially at pH 7 and 8. To quantify the spatial distribution of [1O2], we combined electrostatic models with Latch and McNeill's three-phase distribution model. Modeling results for Suwannee River humic acid (SRHA) yield a surface [1O2] of ∼60 pM, which is ∼96-fold higher than the aqueous-phase [1O2] measured with FFA. This value is in agreement with prior reports that determined 1-3 orders of magnitude higher [1O2] in the DOM phase compared to bulk solution. Overall, this work expands the knowledge base of DOM microheterogeneous photochemistry by showing that diverse DOM isolates exhibit this phenomenon. In addition, the dual-probe approach and electrostatic modeling offer a new way to gain mechanistic insight into the spatial distribution of 1O2 and potentially other photochemically produced reactive intermediates.

A fatal case of pneumonia and sepsis caused by sequence type 398 methicillin-susceptible Staphylococcus aureus carrying Pantone-Valentine leukocidin in China.

Staphylococcus aureus (S. aureus) sequence type 398 (ST398) has aroused great concern for its spread throughout the world. ST398 community-acquired MRSA (CA-MRSA) has been given greater emphasis because of its high virulence and high probability of treatment failure. Herein, A 22-year-old male was admitted to our hospital with a history of fever, chest pain and dyspnea for 2 days. A chest CT scan showed infiltrative and nodular shadows. The sequence type of the isolates from blood culture was ST398, the virulence genes detected was PVL gene (lukS-PV and lukF-PV). Despite resuscitation efforts, he died of multiple organ failure on admission 3rd day. This is the first described case of severe pneumonia and sepsis due to hematogenous spread of scalp furuncles caused by Panton-Valentine leukocidin (PVL) positive community-acquired methicillin-susceptible S. aureus (CA-MSSA) ST398 strains in an immunocompentent adult in mainland China. This report highlight the emergence CA-PVL-MSSA ST398 infection and its association with life-threatening infections. Early decolonization and identification of ST398 is critical. Severe skin and soft tissue infections should be suspected for ST398 PVL-MSSA.

Cryptococcal Meningitis in a Patient with Sjogren's Syndrome: a Case Report.

BACKGROUND: Cryptococcal meningitis (CM) is a life-threatening infectious disease and causes high morbidity and mortality. No information about Cryptococcal meningitis in populations with Sjogren's syndrome (SS) was available. METHODS: This report details the first case of Cryptococcal meningitis in a 75-year-old female patient with 10-years history of Sjogren's syndrome. RESULTS: Detailed findings of C. neoformans from CSF examinations, including routine examination, India ink stain, immunological test, culturing, mass spectrum analysis and molecular biology identification were all delineated in this case, which facilitated understanding of detection methods in C. neoformans infection. The etiological exploration was initiated from a positive finding of yeast cells in routine examination of unstained CSF in the present case. Morphology description of C. neoformans in unstained CSF was depicted for the first time. CONCLUSIONS: Clinicians should consider the possible complication of Cryptococcal meningitis when patients with Sjogren's syndrome show neurological symptoms. Importance of screening yeast cells from unstained CSF for routine examination was emphasized, which may reduce errors in cell counting and trigger further etiological ex-ploration of C. neoformans infection in laboratory and clinical practice.

Portfolio Seismic Loss Estimation and Risk-based Critical Scenarios for Residential Wooden Houses in Victoria, British Columbia, and Canada.

This study presents a city-wide seismic risk assessment of single-family wooden houses in Victoria, British Columbia, and Canada. The novelty and uniqueness of this study include considerations of detailed building-by-building exposure model for residential houses, current national seismic hazard model for Canada, and rigorous seismic fragility modeling of wooden houses based on nonlinear dynamic analysis of structures subjected to mainshock-aftershock sequences. A full consideration of stochastic event scenarios in probabilistic seismic risk analysis allows the identification of critical scenarios from overall regional seismic risk perspectives and provides valuable insights in informing earthquake disaster risk management actions. Outputs from the developed catastrophe model for Victoria are compared with the empirical model that was developed based on insurance claim data from the 1994 Northridge earthquake. Results of the seismic loss calculations highlight the importance of seismic resistance of the existing houses and of aftershock effects. The integrated use of the outputs from the advanced catastrophe model facilitates risk-based identification of critical earthquake scenarios, which are useful for different stakeholders for earthquake risk management purposes.

Resveratrol and Puerarin loaded polymeric nanoparticles to enhance the chemotherapeutic efficacy in spinal cord injury.

Spinal cord injury includes inflammation and apoptosis of neurons, which is difficult to cure by systemic drug administration. Administration of natural active compounds (resveratrol and also Puerarin) by advance drug delivery technology improves the patient's conditions. Oil-in-water emulsion method was utilized to prepare resveratrol as well as puerarin loaded PLGA nanoparticles. The nanoparticles were subjected to mean zeta potential, mean particle size, encapsulation efficiency as well as in vitro drug release studies. The biochemical parameters i.e. malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), advanced oxidation products (AOPP), catalase (CAT) and nitrite/nitrate levels were tested for the loaded nanoparticles. Reperfusion injury induced rats treated with 10 mg/kg resveratrol and puerarin loaded nanoparticles protects spine from ischemia injury and supports biological parameters. The mean particle size varies from 238 nm to 274 nm and also particle size distribution was mono-dispersed (0.239 to 0.318). Zeta potential value of nanoparticles was observed to be -12.6 ± 2.1 mV. Optimized nanoparticles reveals 72% -79% of drug release over 36 h by diffusion mechanism. Significantly, lowers the levels of plasma nitrite/nitrate level as well as phosphorylation of p38MAPK pathways in reperfusion injury induced rats. The resveratrol and puerarin loaded nanoparticles decreases free radicals produced by reperfusion injury induced rats, as well as decrease of oxidative stress because of IRI. Resveratrol and puerarin loaded nanoparticles decreases GSH, SOD and CAT antioxidant level, which helps in overall health improvement of patients.

1.7 µm band narrow-linewidth tunable Raman fiber lasers pumped by spectrum-sliced amplified spontaneous emission.

A 1.7 µm band tunable narrow-linewidth Raman fiber laser based on spectrally sliced amplified spontaneous emission (SS-ASE) and multiple filter structures is proposed and experimentally demonstrated. In this scheme, an SS-ASE source is employed as a pump source in order to avoid stimulated Brillouin scattering. The ring configuration includes a 500 m long high nonlinear optical fiber and a 10 km long dispersion shifted fiber as the gain medium. A segment of un-pumped polarization-maintaining erbium-doped fiber is used to modify the shape of the spectrum. Furthermore, a nonlinear polarization rotation scheme is applied as the wavelength selector to generate lasers. A high-finesse ring filter and a ring filter are used to narrow the linewidth of the laser, respectively. We demonstrate tuning capabilities of a single laser over 28 nm between 1652 nm and 1680 nm by adjusting the polarization controller (PC) and tunable filter. The tunable laser has a 0.023 nm effective linewidth with the high-finesse ring filter. The stable multi-wavelength laser operation of up to four wavelengths can be obtained by adjusting the PC carefully when the pump power increases.

Effects of high-intensity focused ultrasound on cisplatin-resistant human lung adenocarcinoma in vitro and in vivo.

It is widely accepted that high-intensity focused ultrasound (HIFU) is a minimally invasive treatment option for different tumors, but its roles and the corresponding mechanism in cisplatin (DDP) chemoresistance in lung adenocarcinoma (LA) remain unclear. In this study, we investigated the response of DDP-resistant LA cells to HIFU and its underlying molecular mechanisms using molecular biology techniques. It was found that HIFU exposure inhibited the proliferation of DDP-resistant A549 (A549/DDP) cells through arresting cell cycle at the G1/G0 phase via the Cyclin-dependent pathway and promoting apoptosis in a Bcl-2-dependent manner. Furthermore, the results also showed that HIFU exposure could down-regulate the expressions of MDR1, MRP1, and LRP mRNAs, as well as P-gp, MRP1, and LRP proteins related to drug resistance in A549/DDP cells. In vivo experiments also demonstrated that HIFU could reduce the size and mass of subcutaneously transplanted tumors produced by A549/DDP cells through mediating Cyclin-dependent and Bcl-2-dependent pathways. These results suggested that HIFU treatment could inhibit the proliferation of DDP-resistant lung cancer cells and might be a novel therapeutic method for patients with DDP resistance.

Polarization control strategy of a laser communication terminal with a periscopic scanner using dual rotating waveplates.

We assessed the problem of low mixing efficiency caused by unstable signal polarization because of a moving reflector in a laser communication terminal with a periscopic scanner. A real-time polarization compensation method based on rotating waveplates is presented, which keeps the receiving signal light polarization at 45° linear polarized and improves system mixing efficiency. A geometric model of the laser communication terminal was first established, its polarization transmission characteristics were analyzed by three-dimensional polarization tracks, and a system polarization transmission matrix was calculated. The relationship between scan angle and polarization of the output signal was simulated. The connections between a polarization-compensating λ/4 waveplate and the λ/2 waveplate rotation angle and scan angle were established. These findings will pave the way for real-time polarization control technology for coherent free-space laser communications.

Pyrrolidine dithiocarbamate protects pancreatic ß-cells from oxidative damage through regulation of FoxO1 activity in type 2 diabetes rats.

Pyrrolidine dithiocarbamate (PDTC) can lower the blood glucose level and improve the insulin sensitivity in diabetic rats. However, the mechanisms underlying this effect of PDTC treatment in diabetic rats remained uncertain. In this study, we evaluated the mechanisms by which PDTC conferred protection against oxidative damage to pancreatic islet ß-cells in rats with experimental type 2 diabetes mellitus (DM). DM in the rats was elicited by long-term high-fat diet accompanied with a single intraperitoneal (i.p.) injection of a low dose of streptozotocin. After a 7-day administration of PDTC (50 mg/kg/day i.p.), blood glucose levels were measured and pancreatic tissues were collected for the determination of various biochemical and enzymatic activities using immunohistochemistry, immunofluorescence, and western blot techniques. The percentage of apoptotic pancreatic islet ß-cells was detected by flow cytometry. The results showed that diabetic rats had elevated blood glucose levels and insulin resistance, accompanied with an increase in malondialdehyde content, nitrotyrosine production, and inducible nitric oxide synthase expression. A decrease in superoxide dismutase and glutathione peroxidase activities was also observed in DM rats, culminating with elevated ß-cell apoptosis. PDTC treatment significantly reduced the oxidative damage and the ß-cell apoptosis, and also increased the insulin production through down-regulating FoxO1 acetylation and up-regulating nuclear PDX-1 level. These data suggested that PDTC can protect islet ß-cells from oxidative damage and improve insulin production through regulation of PDX-1 and FoxO1 in a DM rat model.

[Expression and diagnostic value of growth differentiation factor 15 in patients with septic cardiomyopathy].

OBJECTIVE: To explore the expression of growth differentiation factor 15 (GDF15) in patients with septic cardiomyopathy and its value in the diagnosis of septic cardiomyopathy. METHODS: A observational study was conducted. Fifty patients with septic cardiomyopathy admitted to Shanxi Bethune Hospital from May 2022 to March 2023 were selected as the experimental group. Forty-six patients with acute coronary syndrome (ACS) in the same period were selected as the case control group. Forty-nine healthy adults were selected as the healthy control group, who underwent physical examination in the physical examination center during the same period. The demographic data and clinical indicators of the subjects were recorded, and the serum GDF15 level was detected by double sandwich enzyme-linked immunosorbent assay (ELISA). And the 28-day outcome of patients with septic cardiomyopathy was followed up, and they were divided into survival group and death group. The serum GDF15 level of subjects in each group and its correlation with clinical indicators were analyzed and compared. Binary Logistic regression was used to analyze the risk factors of septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was used to evaluate the value of GDF15 in the diagnosis of septic cardiomyopathy. RESULTS: The serum GDF15 level of experimental group was significantly higher than that in the case control group and healthy control group [ng/L: 314.14 (221.96, 469.56) vs. 39.08 (26.27, 76.85), 6.39 (3.35, 14.42), both P < 0.01]. Correlation analysis showed that serum GDF15 level in patients with septic cardiomyopathy were correlated with cardiac troponin I (cTnI, r = 0.295, P = 0.038), brain natriuretic peptide (BNP, r = 0.464, P = 0.009), sequential organ failure assessment (SOFA, r = 0.363, P = 0.010) and acute physiology and chronic health evaluation II (APACHE II, r = 0.316, P = 0.025). However, there was no significant correlation with white blood cell count, neutrophil count, lymphocyte count, procalcitonin, C-reactive protein, lactic acid, albumin and other clinical indicators (r values were 0.086, 0.123, -0.051, 0.055, 0.119, 0.199, -0.234, all P > 0.05). Serum GDF15 level, SOFA score and APACHE II score in the death group (30 cases) were significantly higher than those in the survival group [20 cases; GDF15 (ng/L): 382.93±159.61 vs. 289.66±158.46, SOFA: 10.00 (7.00, 12.00) vs. 6.00 (5.00, 9.50), APACHE II: 21.70±6.07 vs. 14.85±7.57, all P < 0.05]. Binary Logistic regression analysis showed that serum GDF15 was an independent risk factor for the onset of septic cardiomyopathy [odds ratio (OR) = 1.062, 95% confidence interval (95%CI) was 1.011-1.115, P = 0.016]. ROC curve showed that the area under the curve (AUC) of GDF15 for predicting septic cardiomyopathy was 0.971, the specificity was 100%, and the sensitivity was 90.3%. CONCLUSIONS: The serum GDF15 level of patients with septic cardiomyopathy is significantly increased, and GDF15 may be used as an effective biomarker for the early diagnosis of septic cardiomyopathy.

Lemierre's syndrome complicating multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260: Case report and review.

We described a case of a 24-year-old man with multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260. This is the first described case of Lemierre's syndrome with multiple organ failure due to F. necrophorum subsp. funduliforme F1260 in an adult in China. Our study highlights that there may be a risk of misdiagnosis based solely on typical manifestations of internal jugular vein thrombophlebitis, metastatic lesions, and F. necrophorum isolated from blood cultures or normally sterile sites. Clinicians should be cognizant of the potential utility of metagenomic next-generation sequencing in facilitating early pathogen detection in severe infections, thus enabling timely and appropriate administration of antibiotics to reduce mortality rates and improve prognosis.

An ultra-sensitive biosensor based on surface plasmon resonance and weak value amplification.

An ultra-sensitive phase plasmonic sensor combined with weak value amplification is proposed for the detection of IgG, as a model analyte. Phase detection is accomplished by self-interference between the p-polarization and the s-polarization of the light. With the principles of weak value amplification, a phase compensator is used to modulate the coupling strength and enhance the refractive index sensitivity of the system. On a simple Au-coated prism-coupled surface plasmon resonance (SPR) structure, the scheme, called WMSPR, achieves a refractive index sensitivity of 4.737 × 104 nm/RIU, which is about three times higher than that of the conventional phase-based approach. The proposed WMSPR biosensor gives great characteristics with a high resolution of 6.333 × 10-8 RIU and a low limit of detection (LOD) of 5.3 ng/mL. The results yield a great scope to promote the optimization of other SPR biosensors for high sensitivity.

Multi role ChatGPT framework for transforming medical data analysis.

The application of ChatGPTin the medical field has sparked debate regarding its accuracy. To address this issue, we present a Multi-Role ChatGPT Framework (MRCF), designed to improve ChatGPT's performance in medical data analysis by optimizing prompt words, integrating real-world data, and implementing quality control protocols. Compared to the singular ChatGPT model, MRCF significantly outperforms traditional manual analysis in interpreting medical data, exhibiting fewer random errors, higher accuracy, and better identification of incorrect information. Notably, MRCF is over 600 times more time-efficient than conventional manual annotation methods and costs only one-tenth as much. Leveraging MRCF, we have established two user-friendly databases for efficient and straightforward drug repositioning analysis. This research not only enhances the accuracy and efficiency of ChatGPT in medical data science applications but also offers valuable insights for data analysis models across various professional domains.

Unpacking the effects of natural gas price transmission on electricity prices in Nordic countries.

Since the Russia-Ukraine war in February 2022, European electricity prices have experienced considerable turbulence, primarily attributed to a shortage in the natural gas supply. We investigate the relationship between natural gas prices in the European continent and electricity prices in Nordic countries before and after the outbreak of war. Despite the low proportion of natural gas electricity generation, the empirical analysis reveals both direct and indirect transmission paths for natural gas prices in Nordic countries. Meanwhile, the theoretical analysis demonstrates how Nordic renewable (wind and solar) and other non-gas generators exercise market power through price bidding in the anticipation of an increase in gas prices or a shortage of gas supply, which results in higher electricity prices. Understanding the underlying factors and dynamics driving substantial price fluctuations in the Nordic electricity market is essential for comprehending the intricate interconnections within the European energy landscape.

Optical Label-Free Aptasensor Based on Weak Value Amplification for Real-Time and Ultrasensitive Detection of IgE.

Allergy is a prevalent disease, and the potential allergic population is expanding with industrialization and changes in people's living standards. Serum immunoglobulin E (IgE) level is one of the critical indicators for determining allergy. Here, we proposed a simple, real-time monitoring, low chip cost, label-free aptamer biosensing strategy based on weak value amplification (WVA) for the quantitative detection of IgE in serum samples, enabling early and accurate diagnosis of allergic or hypersensitive patients. The aptasensor combined an imaging weak measurement system with the high specificity of the aptamer for the marker IgE. By modifying the amino group at the 3-terminal end, the anti-IgE aptamers can attach to a dopamine-modified prism's surface and selectively recognize IgE in human serum. In the presence of IgE, a specific binding reaction occurred, resulting in a change in the refractive index of the reactive region's surface, manifested as a change in the light intensity of the camera acquired experimental images. As the concentration of IgE increased, the relative light intensity advanced sequentially. The WVA-aptasensing strategy achieved a wide detection range of 0.01 ng/mL to 2 µg/mL in phosphate buffered saline buffer, with the resolution as low as 4.3 pg/mL. IgE testing experiments in human serum have proved the feasibility of our methods in detecting complex samples. In addition, the method specifically recognized IgE without interference from other proteins. We believe that our proposed sensing strategy opens up new possibilities for ultrahigh sensitivity screening of IgE and can be expanded to detecting other biomolecules.

Realization of high-performance biosensor through sandwich analysis utilizing weak value amplification.

A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis and detection of low-concentration targets. 3D printed channels and sodium chloride solution were employed to ensure reproducibility, reliability, and stability of the measurements for calibration. The sandwich structure demonstrated enhanced responsiveness in the proposed optical biosensor through a comparative analysis of the direct assay and sandwich assay for detecting alpha-fetoprotein (AFP) at the same concentration. By optimizing the binding sequences of the coating antibody, target, and detection antibody in the sandwich method, a more suitable sandwich sensing approach based on weak value amplification was achieved. With this approach, the limit of detection (LOD) of 6.29 ng/mL (pM level) for AFP in PBS solution was achieved. AFP testing and regeneration experiments in human serum have proved the feasibility of our methods in detecting complex samples and the reusability of sensing chips. Additionally, the method demonstrated excellent selectivity for unpaired antigens. The efficacy of this methodology was evaluated by simultaneously detecting AFP, carcinoembryonic antigen (CEA), and CA15-3 on a singular sensor chip. In conclusion, the label-free sandwich immunoassay sensing scheme holds promise for advancing the proposed optical sensors based on weak value amplification in early diagnosis and prevention applications. Compared to other biomarker detection methods, it will be easier to promote in practical applications.

Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow. The translocation, (t)(4;14), results in high-risk MM with limited treatment alternatives. Thus, there is an urgent need for identification and validation of potential treatments for this MM subtype. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To elucidate the molecular basis and search for potential effective drugs of t(4;14) MM subtype by employing a comprehensive approach. METHODS: The transcriptional signature of t(4;14) MM was sourced from the Gene Expression Omnibus. Two datasets, GSE16558 and GSE116294, which included 17 and 15 t(4;14) MM bone marrow samples, and five and four normal bone marrow samples, respectively. After the differentially expressed genes were identified, the Cytohubba tool was used to screen for hub genes. Then, the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Using the STRING database and Cytoscape, protein-protein interaction networks and core targets were identified. Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis, respectively. RESULTS: In this study, a total of 258 differentially expressed genes with enriched functions in cancer pathways, namely cytokine receptor interactions, nuclear factor (NF)-κB signaling pathway, lipid metabolism, atherosclerosis, and Hippo signaling pathway, were identified. Ten hub genes (cd45, vcam1, ccl3, cd56, app, cd48, btk, ccr2, cybb, and cxcl12) were identified. Nine drugs, including ivermectin, deforolimus, and isoliquiritigenin, were predicted by the Connectivity Map database to have potential therapeutic effects on t (4;14) MM. In molecular docking, ivermectin showed strong binding affinity to all 10 identified targets, especially cd45 and cybb. Ivermectin inhibited t(4;14) MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro. Furthermore, ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14) MM cells. CONCLUSION: Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.

Uncovering the key factors influencing sustainable green production behavior among Chinese medicinal herb growers.

Promoting green production behavior among farmers is crucial for enhancing income, improving industrial efficiency, and ensuring ecological security. This study analyzes the determinants of green production behavior among farmers in Cheifeng, China, Using a binary logistic model on a sample of 860 microdata. The result of empirical analysis pointed out that the implementation rate of rural households was low at 54.5 %, highlighting the need for intervention. The results suggest that age, party members, total income, total area, irrigation conditions, market, policy, social factors, and knowledge transfer ability significantly influence green production behavior. Among these factors, age, party member, total area, irrigation conditions, and knowledge transfer ability have negative effects, while other factors positively affect green production. To promote green production behavior, this study recommends improving access to information, developing a training system, enhancing quality and safety information disclosure, establishing traceability mechanisms, and providing policy subsidies. This stud also highlights the need to strengthen publicity, technical guidance, and media persuasion for promoting the green production of Chinese medicinal materials.