Numerical Investigation of Heat Transfer and Development in Spherical Condensation Droplets.

This study establishes thermodynamic assumptions regarding the growth of condensation droplets and a mathematical formulation of droplet energy functionals. A model of the gas-liquid interface condensation rate based on kinetic theory is derived to clarify the relationship between condensation conditions and intermediate variables. The energy functional of a droplet, derived using the principle of least action, partially elucidates the inherent self-organizing growth laws of condensed droplets, enabling predictive modeling of the droplet's growth. Considering the effects of the condensation environment and droplet heat transfer mechanisms on droplet growth dynamics, we divide the process into three distinct stages, marked by critical thresholds of 105 nm3 and 1010 nm3. Our model effectively explains why the observed contact angle fails to reach the expected Wenzel contact angle. This research presents a detailed analysis of the factors affecting surface condensation and heat transfer. The predictions of our model have an error rate of less than 3% error compared to baseline experiments. Consequently, these insights can significantly contribute to and improve the design of condensation heat transfer surfaces for the phase-change heat sinks in microprocessor chips.

In vivo safety evaluation method for nanomaterials for cancer therapy.

Nanomaterials are extensively used in the diagnosis and treatment of cancer and other diseases because of their distinctive physicochemical properties, including the small size and ease of modification. The approval of numerous nanomaterials for clinical treatment has led to a significant increase in human exposure to these materials. When nanomaterials enter organisms, they interact with DNA, cells, tissues, and organs, potentially causing various adverse effects, such as genotoxicity, reproductive toxicity, immunotoxicity, and damage to tissues and organs. Therefore, it is crucial to elucidate the side effects and toxicity mechanisms of nanomaterials thoroughly before their clinical applications. Although methods for in vitro safety evaluation of nanomaterials are well established, systematic methods for in vivo safety evaluation are still lacking. This review focuses on the in vivo safety evaluation of nanomaterials and explores their potential effects. In addition, the experimental methods for assessing such effects in various disciplines, including toxicology, pharmacology, physiopathology, immunology, and bioinformatics are also discussed.

Corrigendum: Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials.

[This corrects the article DOI: 10.3389/fcvm.2023.1142721.].

A label-free fluorescence sensing strategy based on GlaI-assisted EXPAR for rapid and accurate quantification of human methyltranferase activity.

DNA methylation plays an important role in epigenetic modification. DNA methyltransferase (DNMT) is essential in the DNA methylation process, and its abnormal expression is closely related to cancer. In this study, we propose a novel biosensor platform (DS-GlaI-EXPAR) that combines hemi-methylated double-stranded DNA (dsDNA) as the substrate for DNMT1 with GlaI-assisted isothermal exponential amplification reaction (EXPAR) for rapid, simple, and sensitive detection of DNMT1 activity. The hemi-methylated dsDNA is fully methylated by DNMT1, and GlaI recognizes and cleaves the fully methylated sequence, generating terminal fragments that trigger EXPAR for efficient signal amplification. Whereas hemi-methylated dsDNA without DNMT1 will keep intact and cannot initiate EXPAR. DNMT1 activity can therefore be sensitively quantified by the real-time fluorescence signal of the DS-GlaI-EXPAR platform. The high-efficiency amplification of EXPAR and the recognition of GlaI enable the platform to overcome the inherent cumbersome and time-consuming shortcomings of traditional methods while meeting specificity and sensitivity. This DS-GlaI-EXPAR platform offers an impressively low limit of detection of 0.86 pg/µL and the entire detection process can be completed in a short time of 2.5 h in a single tube. Furthermore, DNMT1 activity detected by this platform in MCF-7 cells was significantly higher than that of HEK293 cells, and the inhibition of Apt. #9 was verified. This DNMT1 activity detection platform is very convenient and effective for the discovery of inhibitors and early cancer diagnosis.

An "AND" Logic-Gated Prodrug Micelle Locally Stimulates Antitumor Immunity.

Materials that can respond to multiple biomarkers simultaneously, acting as an "AND" gate, have the potential to enhance tumor-targeting for drug delivery. In this study, an "AND" logic-controlled release prodrug micelle is developed for codelivering the chemotherapeutic and the stimulator of interferon genes (STING) agonist, enabling precise combinatorial therapy. The drug release is programmed by tumor-enriched boramino acids (BAA) in the tumor microenvironment and intracellular reactive oxygen species (ROS), resulting in enhanced tumor targeting. STING agonist is successfully encapsulated into prodrug micelles through π-π stacking and hydrophobic interactions. These AND logic-gated prodrug micelles can achieve tumor-targeted delivery of STING agonist, leading to significantly enhanced immune activation and antitumor efficacy in vivo. It is expected that this clinically relevant nanoplatform will provide a rational design of an effective immunotherapy combination regimen to convert immunologically "cold" tumors to immunogenic "hot" tumors, addressing the major challenges faced by immunotherapies.

Toehold-Containing Three-Way Junction-Initiated Multiple Exponential Amplification and CRISPR/Cas14a Assistant Magnetic Separation Enhanced Visual Detection of Mycobacterium Tuberculosis.

Rapid and simple nucleic acid detection is significant for disease diagnosis and pathogen screening, especially under specific conditions. However, achieving highly sensitive and specific nucleic acid detection to meet the time and equipment demand remains technologically challenging. In this study, we proposed a magnetic separation enhanced colorimetry biosensor based on a toehold-containing three-way junction (TWJ) induced multiple isothermal exponential amplification and the CRISPR/Cas14a (C-TEC) biosensor. The TWJ template was designed as a Y-X-Y structure. In the presence of the target, the formation of toehold-containing TWJ complex induced primer extension, leading to the generation of amplified single-stranded DNA; this amplified DNA could then bind to either the free TWJ template for EXPAR reaction or the toehold of the TWJ complex for toehold-mediated strand displacement, thereby enabling the recycling of the target. The amplification products could trigger CRISPR/Cas14a for efficient trans-cleavage and release the magnetically bound gold nanoparticle probes for colorimetry detection. Using Mycobacterium tuberculosis 16S rDNA as the target, the proposed C-TEC could detect 16S rDNA down to 50 fM by the naked eye and 20.71 fM by UV-vis detector at 520 nm within 90 min under optimal conditions. We successfully applied this biosensor to clinical isolates of Mycobacterium tuberculosis. In addition, the C-TEC biosensor also showed feasibility for the detection of RNA viruses. In conclusion, the proposed C-TEC is a convenient, fast, and versatile platform for visual detection of pathogen DNA/RNA and has potential clinical applications.

The Mediating Role of Psychological Well-Being in the Relationship Between Self-Management and Quality of Life in Patients With Hypertension.

This study applied a cross-sectional design to examine the relationship between self-management, psychological well-being, and quality of life in patients with hypertension and evaluated the mediation effect of psychological well-being on self-management and quality of life. Through purposive sampling, this study enrolled 255 patients with hypertension from the cardiology department of a teaching hospital in Taiwan. Mediation effects were estimated using linear regression and the Sobel test. Age, number of chronic diseases, waist circumference, self-management, and psychological well-being explained 18.7% of the total variance in quality of life. Psychological well-being partially mediated the effects of self-management on quality of life, with a total effect of 19.2%. Psychological well-being is an important factor correlated with self-management and quality of life in patients with hypertension.

The prognostic role of the preoperative platelet to lymphocyte ratio in laryngeal cancer.

Background: In recent years, several studies have investigated the relationship between platelet to lymphocyte ratio (PLR) and the prognosis of patients with laryngeal cancer, but the results remain controversial. This study aimed to evaluate the prognostic significance of pretreatment PLR in patients with laryngeal cancer. Methods: Up to July 2023, we searched PubMed, PubMed Central, Web of Science, Embase, CNKI and Wanfang databases to collect relevant articles evaluating the relationship between PLR and the prognosis of laryngeal cancer. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using the random effect-model. Results: A total of 14 included studies involving 3220 patients with laryngeal cancer were included. The combined results suggested that elevated PLR was associated with poorer overall survival (HR = 2.21, 95% CI, 1.67 - 2.93, p < 0.001), progression-free survival (HR = 2.54, 95% CI, 1.76-3.66, p < 0.001), recurrence-free survival (HR = 1.87, 95% CI,1.45 - 2.42, p < 0.001), and disease-free survival (HR = 1.46, 95% CI, 1.08-1.98, p < 0.001). Subgroup analysis further confirmed that pretreatment PLR was an independent predictor of OS in laryngeal cancer patients. Conclusion: Higher pretreatment PLR is strongly related to poor prognosis of laryngeal cancer patients. This indicates that PLR has the potential to serve as a valuable biomarker for predicting the prognosis of laryngeal cancer. However, further validations in large prospective cohorts are necessary to confirm its clinical utility and reliability.

Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.

Triple-recognition strategy for one-pot detection of single nucleotide variants by aligner-mediated cleavage-triggered exponential amplification.

The detection of single nucleotide variants (SNVs) is important for the diagnosis and treatment of cancer. To date, researchers have devised several methods to detect SNVs, but most of them are complex and time-consuming. To improve SNVs detection specificity and sensitivity, we developed a triple-recognition strategy, which facilitates aligner-mediated cleavage-triggered exponential amplification (Trec-AMC-EXPAR) for the rapid, specific, and one-pot detection of SNV. Under optimized conditions, Trec-AMC-EXPAR detected two clinically significant SNVs, PIK3CAH1047R and EGFR L858R within 80 min, with a reliable detection of 0.1% SNV in the wide type, which is lower than that of allele-specific PCR (AS-PCR) for detecting SNV. Finally, by spiking into normal human serum samples, mutants mixed with the wild-type targets in different ratios were analyzed, resulting in the relative standard deviation (RSD) of recovery ratios <3%. The findings suggested the potential application of Trec-AMC-EXPAR in clinical disease diagnosis. In summary, the proposed Trec-AMC-EXPAR technique provides a novel fast and convenient method for one-pot detection of SNV with high sensitivity and specificity.

Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials.

Background: Many retrospective studies suggest that risk improvement may be a suitable efficacy surrogate endpoint for pulmonary arterial hypertension (PAH) medication trials. This prospective multicenter study assessed the efficacy of domestic ambrisentan in Chinese PAH patients and observed risk improvement and time to clinical improvement (TTCI) under ambrisentan treatment. Methods: Eligible patients with PAH were enrolled for a 24-week treatment with ambrisentan. The primary efficacy endpoint was 6-min walk distance (Δ6MWD). The exploratory endpoints were risk improvement and TTCI, defined as the time from initiation of treatment to the first occurrence of risk improvement. Results: A total of 83 subjects were enrolled. After ambrisentan treatment, Δ6MWD was significantly increased at week 12 (42.2 m, P < 0.0001) and week 24 (53.4 m, P < 0.0001). Within 24 weeks, risk improvement was observed in 53 (64.6%) subjects (P < 0.0001), which is higher than WHO-FC (30.5%) and TAPSE/PASP (32.9%). Kaplan-Meier analysis of TTCI showed a median improvement time of 131 days and a cumulative improvement rate of 75.1%. Also, TTCI is consistent across different baseline risk status populations (log-rank P = 0.51). The naive group had more risk improvement (P = 0.043) and shorter TTCI (log-rank P = 0.008) than the add-on group, while Δ6MWD did not show significant differences between the two groups. Conclusions: Domestic ambrisentan significantly improved the exercise capacity and risk status of Chinese PAH patients. TTCI has a relatively high positive event rate within 24-week treatment duration. Compared to Δ6MWD, TTCI is not affected by baseline risk status. Additionally, TTCI could identify better improvements in patients, which Δ6MWD does not detect. TTCI is an appropriate composite surrogate endpoint for PAH medication trials. Clinical Trial Registration: NCT No. [ClinicalTrials.gov], identifier [NCT05437224].

Air Combat Intention Recognition with Incomplete Information Based on Decision Tree and GRU Network.

Battlefield information is generally incomplete, uncertain, or deceptive. To realize enemy intention recognition in an uncertain and incomplete air combat information environment, a novel intention recognition method is proposed. After repairing the missing state data of an enemy fighter, the gated recurrent unit (GRU) network, supplemented by the highest frequency method (HFM), is used to predict the future state of enemy fighter. An intention decision tree is constructed to extract the intention classification rules from the incomplete a priori knowledge, where the decision support degree of attributes is introduced to determine the node-splitting sequence according to the information entropy of partitioning (IEP). Subsequently, the enemy fighter intention is recognized based on the established intention decision tree and the predicted state data. Furthermore, a target maneuver tendency function is proposed to screen out the possible deceptive attack intention. The one-to-one air combat simulation shows that the proposed method has advantages in both accuracy and efficiency of state prediction and intention recognition, and is suitable for enemy fighter intention recognition in small air combat situations.

Nickel-Catalyzed Amidation of Aryl Alkynyl Acids with Tetraalkylthiuram Disulfides: A Facile Synthesis of Aryl Alkynyl Amides.

Nickel-catalyzed amidation of aryl alkynyl acids using tetraalkylthiuram disulfides as the amine source is described, affording a series of aryl alkynyl amides in good to excellent yields under mild conditions. This general methodology provides an alternative pathway for the synthesis of useful aryl alkynyl amides in an operationally simple manner, which shows its practical synthetic value in organic synthesis. The mechanism of this transformation was explored through control experiments and DFT calculations.

Does Moses technology enhance the efficiency and outcomes of regular holmium laser lithotripsy? Results of a pooled analysis of comparative studies.

Holmium laser lithotripsy is currently the optimum standard for surgical treatment of upper urinary calculi. This study aims to evaluate the clinical efficacy and safety of Moses compared with conventional holmium laser lithotripsy for the treatment of patients with upper urinary calculi. We conducted a systematic search using multiple databases (PubMed/Medline, Scopus, Web of Science, and ClinicalTrials.gov) until June 2022. Clinical trials comparing Moses and conventional holmium laser lithotripsy were included. Analysis was performed using RevMan version 5.4.4 software. Four studies with 892 patients were included. There were no significant differences regarding stone-free rate (mean difference [MD] 1.19, 95% CI 0.54, 2.64, p = 0.66), operative time (MD - 9.31, 95% CI - 21.11, 2.48, p = 0.12), fragmentation time (MD - 1.71, 95% CI - 11.81, 8.38, p = 0.74), total energy used (MD 1.23, 95% CI - 0.44, 2.90, p = 0.15), auxiliary procedures (MD 0.38, 95% CI 0.08, 1.90, p = 0.24), and overall complications (odds ratio [OR] 0.70, 95% CI 0.30, 1.66, p = 0.42) between the groups. However, the laser working time (MD - 0.94, 95% CI - 1.20, - 0.67, p < 0.001) of Moses technology was shorter than that of conventional technology. Moses technology has similar outcomes to regular technology in terms of safety and efficacy. Given the higher operating costs of the Moses technology, further study is required to determine whether there are benefits to this new technology.

Morroniside induces cardiomyocyte cell cycle activity and promotes cardiac repair after myocardial infarction in adult rats.

Introduction: Acute myocardial infarction (AMI) is characterized by the loss of cardiomyocytes, which impairs cardiac function and eventually leads to heart failure. The induction of cardiomyocyte cell cycle activity provides a new treatment strategy for the repair of heart damage. Our previous study demonstrated that morroniside exerts cardioprotective effects. This study investigated the effects and underlying mechanisms of action of morroniside on cardiomyocyte cell cycle activity and cardiac repair following AMI. Methods: Neonatal rat cardiomyocytes (NRCMs) were isolated and exposed to oxygen-glucose deprivation (OGD) in vitro. A rat model of AMI was established by ligation of the left anterior descending coronary artery (LAD) in vivo. Immunofluorescence staining was performed to detect newly generated cardiomyocytes. Western blotting was performed to assess the expression of cell cycle-related proteins. Electrocardiography (ECG) was used to examine pathological Q waves. Masson's trichrome and wheat germ agglutinin (WGA) staining assessed myocardial fibrosis and hypertrophy. Results: The results showed that morroniside induced cardiomyocyte cell cycle activity and increased the levels of cell cycle proteins, including cyclin D1, CDK4, cyclin A2, and cyclin B1, both in vitro and in vivo. Moreover, morroniside reduced myocardial fibrosis and remodeling. Discussion: In conclusion, our study demonstrated that morroniside stimulates cardiomyocyte cell cycle activity and cardiac repair in adult rats, and that these effects may be related to the upregulation of cell cycle proteins.

Acoustic Sensing Based on Online Handwritten Signature Verification.

Handwritten signatures are widely used for identity authorization. However, verifying handwritten signatures is cumbersome in practice due to the dependency on extra drawing tools such as a digitizer, and because the false acceptance of a forged signature can cause damage to property. Therefore, exploring a way to balance the security and user experiment of handwritten signatures is critical. In this paper, we propose a handheld signature verification scheme called SilentSign, which leverages acoustic sensors (i.e., microphone and speaker) in mobile devices. Compared to the previous online signature verification system, it provides handy and safe paper-based signature verification services. The prime notion is to utilize the acoustic signals that are bounced back via a pen tip to depict a user's signing pattern. We designed the signal modulation stratagem carefully to guarantee high performance, developed a distance measurement algorithm based on phase shift, and trained a verification model. In comparison with the traditional signature verification scheme, SilentSign allows users to sign more conveniently as well as invisibly. To evaluate SilentSign in various settings, we conducted comprehensive experiments with 35 participants. Our results reveal that SilentSign can attain 98.2% AUC and 1.25% EER. We note that a shorter conference version of this paper was presented in Percom (2019). Our initial conference paper did not finish the complete experiment. This manuscript has been revised and provided additional experiments to the conference proceedings; for example, by including System Robustness, Computational Overhead, etc.

Down-regulating Interleukin-22/Interleukin-22 binding protein axis promotes inflammation and aggravates diet-induced metabolic disorders.

The prevalence of metabolic diseases has become a severe public health problem. Previously, we reported that Interleukin-22 (IL-22) was independently associated with type 2 diabetes mellitus and cardiovascular disease, and could protect endothelial cells from glucose- and lysophosphatidylcholine-induced injury. The activity of IL-22 is strongly regulated by IL-22-binding protein (IL-22BP). The aim of this investigation was to determine the effect of IL-22/IL-22BP axis on glucolipid metabolism. Serum IL-22 and IL-22BP expression in metabolic syndrome (MetS) patients and healthy controls was examined. IL-22BP-knockout (IL-22ra2-/-) and wild-type (WT) mice were fed with control diet (CTD) and high-fat diet (HFD) for 12 weeks. The IL-22 related pathway expression, the glucolipid metabolism, and inflammatory markers in mice were examined. Serum IL-22 and IL-22BP levels were found significantly increased in MetS patients (p < 0.001). IL-22BP deficiency down-regulated IL-22-related pathway, aggravated glucolipid metabolism disorder, and promoted inflammation in mice. Collectively, this work deepens the understanding of the relationship between IL-22/IL-22BP axis and metabolism disorders, and identified that down-regulation of IL-22/IL-22BP axis promotes metabolic disorders in mice.

A sensing strategy combining T7 promoter-contained DNA probe with CRISPR/Cas13a for detection of bacteria and human methyltransferase.

Abnormal DNA methylation is closely related to the occurrence and development of many diseases. The determination of human DNA methyltransferase activity and the screening of its inhibitors are extreme important for the diagnosis and the treatment of methylation-related diseases in clinic. Most of the current detection methods have the disadvantages of sophisticated design, high cost and low detection limit. By combining T7 promoter-contained DNA probe as the substrate for methyltransferase with CRISPR/Cas13a sensing strategy, a novel fluorescent sensing platform is designed to achieve simple, specific, sensitive detection of bacteria DNA methyltransferase (DNA-(N-6-adenine)-methyltransferase, Dam MTase) and also human methyltransferase (DNA (cytosine-5)-methyltransferase 1, Dnmt1). A hairpin DNA probe designed for Dam MTase and a double strand DNA probe for Dnmt1 are both methylated followed by the methylation-dependent site-specific cleavage, which result a T7 promoter-contained product and a T7 promoter-free one to respectively open and close the transcription and subsequent CRISPR/Cas13a target-initiated cleavage of fluorescence-labeled reporter RNA. In virtue of the specificity of methylation-dependent cleavage of probe, the efficient transcription amplification and CRISPR/Cas13a sequence-specific sensing, this strategy exhibited remarkable specificity and sensitivity, with the limit of detection of 3.10 × 10-5 U/mL for Dam MTase. Moreover, Dnmt1 activity in MCF-7 cells was detected and the inhibition of Apt. #9 was evaluated. This strategy for methyltransferase detection is convenient and efficient for inhibitor discovery and early cancer diagnosis.

Roles of the nucleus in leukocyte migration.

Leukocytes patrol our bodies in search of pathogens and migrate to sites of injury in response to various stimuli. Rapid and directed leukocyte motility is therefore crucial to our immunity. The nucleus is the largest and stiffest cellular organelle and a mechanical obstacle for migration through constrictions. However, the nucleus is also essential for 3D cell migration. Here, we review the roles of the nucleus in leukocyte migration, focusing on how cells deform their nuclei to aid cell motility and the contributions of the nucleus to cell migration. We discuss the regulation of the nuclear biomechanics by the nuclear lamina and how it, together with the cytoskeleton, modulates the shapes of leukocyte nuclei. We then summarize the functions of nesprins and SUN proteins in leukocytes and discuss how forces are exerted on the nucleus. Finally, we examine the mechanical roles of the nucleus in cell migration, including its roles in regulating the direction of migration and path selection.

Comparison of Efficacy and Safety Between Immunotherapy and Docetaxel Monotherapy in NSCLC Patients.

Objective: Meta analysis was used to compare the efficacy and safety of immune checkpoint inhibitor and docetaxel in the treatment of non-small cell lung cancer. Methods: CNKI, CBM, PubMed, EMBASE, Cochrane Library, web of science and other databases were searched by computer, and the randomized controlled trials of immune checkpoint inhibitors and docetaxel in the treatment of NSCLC published as of February 2022 were collected. Two researchers searched independently, screened the literature and extracted the data according to the nanodischarge criteria, and used Revman5.4. The included studies were statistically analyzed, and publication bias was analyzed with Egger test in Stata12. Results: A total of 8 RCTs were included, including 2444 cases treated with immune checkpoint inhibitors and 2097 cases treated with docetaxel. Compared with docetaxel, the overall survival (HR = 1.40, 95%CI: 1.30-1.50, P < 0.00001) and progression free survival (HR = 1.22, 95%CI: 1.13-1.32, P < 0.00001) of NSCLC treated with ICIs were longer. The risk ratio of any grade of adverse reactions (HR = 0.41, 95%CI: 0.32-0.52, P < 0.00001) and above grade III adverse reactions (HR = 0.27, 95%CI: 0.18-0.41, P < 0.00001) in the treatment of NSCLC with ICIs was lower. There was no publication bias in Egger test. Conclusion: Compared with docetaxel, immune checkpoint inhibitor treatment can improve the clinical efficacy of NSCLC patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for NSCLC patients.