Studying the Effects and Competitive Mechanisms of YOYO-1 on the Binding Characteristics of DOX and DNA Molecules Based on Surface-Enhanced Raman Spectroscopy and Molecular Docking Techniques.

Revealing the interaction mechanisms between anticancer drugs and target DNA molecules at the single-molecule level is a hot research topic in the interdisciplinary fields of biophysical chemistry and pharmaceutical engineering. When fluorescence imaging technology is employed to carry out this kind of research, a knotty problem due to fluorescent dye molecules and drug molecules acting on a DNA molecule simultaneously is encountered. In this paper, based on self-made novel solid active substrates NpAA/(ZnO-ZnCl2)/AuNPs, we use a surface-enhanced Raman spectroscopy method, inverted fluorescence microscope technology, and a molecular docking method to investigate the action of the fluorescent dye YOYO-1 and the drug DOX on calf thymus DNA (ctDNA) molecules and the influencing effects and competitive relationships of YOYO-1 on the binding properties of the ctDNA-DOX complex. The interaction sites and modes of action between the YOYO-1 and the ctDNA-DOX complex are systematically examined, and the DOX with the ctDNA-YOYO-1 are compared, and the impact of YOYO-1 on the stability of the ctDNA-DOX complex and the competitive mechanism between DOX and YOYO-1 acting with DNA molecules are elucidated. This study has helpful experimental guidance and a theoretical foundation to expound the mechanism of interaction between drugs and biomolecules at the single-molecule level.

"Gear-driven"-type chirality transfer of tetraphenylethene-based supramolecular organic frameworks for peptides in water.

Chirality transfer for natural chiral biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we report the synthesis and characterization of a series of achiral supramolecular organic frameworks (SOF-1, SOF-2, and SOF-3), constructed from cucurbit[8]uril (CB[8]) and tetraphenylethene (TPE) derivatives (1, 2, and 3), respectively, as chirality-sensing platforms to explore their chirality transfer mechanism for peptides in water. Given the right-handed (P) and left-handed (M) rotational conformation of TPE units and the selective binding of CB[8] to aromatic amino acids, these achiral SOFs can be selectively triggered in water by peptides containing N-terminal tryptophan (W) and phenylalanine (F) residues into their P- or M-rotational conformation, exhibiting significantly different circular dichroism (CD) spectra. Although various peptides have the same l-type chiral configuration, they can induce positive CD signals of SOF-1 and negative CD signals of SOF-2 and SOF-3, respectively. Based on the structural analysis of the linkage units between CB[8] and TPE units in these SOFs, a "gear-driven"-type chirality transfer mechanism has been proposed to visually illustrate the multiple-step chirality transfer process from the recognition site in the CB[8]'s cavity to TPE units. Furthermore, by utilizing the characteristic CD signals generated through the "gear-driven"-type chirality transfer, these SOFs can serve as chiroptical sensor arrays to effectively recognize and distinguish various peptides based on their distinctive CD spectra.

Empyema caused by Actinomyces odontolyticus: A case report.

RATIONALE: Actinomyces odontolyticus causes a rare, chronic granulomatous infection that is frequently associated with immunocompromised states. A odontolyticus can cause infection in multiple organs, but empyema is rare. PATIENT CONCERNS: We report a case of empyema caused by A odontolyticus. The patient was a 64-year-old man. He was admitted to the hospital with a 5-day history of fever and dyspnea. He had caries and sequelae of cerebral apoplexy. DIAGNOSES: Metagenome next generation sequencing of pleural effusion was positive for A odontolyticus. Pathogen was identified by biphasic culture of pleural effusion fluid. INTERVENTIONS: According to the drug sensitivity test, linezolid 0.6 g twice daily and clindamycin 0.6 g 3 times a day were administered intravenously. Thoracic drainage was initially performed, but the drainage was not sufficient. Medical thoracoscopy was performed to fully drain the pleural effusion. OUTCOMES: After anti-infection and medical thoracoscopic therapy, the symptoms of this patient improved. LESSONS: Microbial metagenome sequencing can find pathogens that are difficult to culture by traditional methods. Adequate drainage was the key to the treatment of empyema. Medical thoracoscopy was recommended to remove the pleural effusion and spoilage when thoracic drainage is difficult. The common clinical features of A odontolyticus include a mass or swelling, abdominal disease, dental disease, and subcutaneous abscesses. Microbial metagenome sequencing can find pathogens that are difficult to culture by traditional methods. Adequate drainage was the key to the treatment of empyema. Medical thoracoscopy was recommended to remove the pleural effusion and spoilage when thoracic drainage is difficult.

Application of ultrasound-guided medical thoracoscopy in patients with small amounts or without pleural effusion.

BACKGROUND: Pleural disease is a common clinical condition, and some patients present with a small amount of pleural effusion or no pleural effusion. It is difficult to diagnose such patients in clinical practice. Medical thoracoscopy is the gold standard for the diagnosis of pleural effusion with unknown origin, and guidelines recommend that pneumothorax should be induced in such patients before medical thoracoscopy examination. However, the process of inducing pneumothorax is tedious and has many complications. Our study was conducted to clarify the value of thoracic ultrasound combined with medical thoracoscopy in patients with small amounts or without pleural effusion to simplify the process of medical thoracoscopy examination. METHODS: In this retrospective study, we included patients who were assigned to complete medical thoracoscopy. Successful completion of medical thoracoscopy in patients was regarded as letting the endoscope get into the pleural cavity and completion of the biopsy. Finally, we analyzed the value of preoperative ultrasound in patients without or with small amounts of pleural effusion. RESULTS: Seventy-two patients were finally included in the study. Among them, 68 patients who underwent ultrasound positioning of the access site successfully completed the examination and four patients failed the examination. Fifty-one cases showed no fluid sonolucent area at the access site, of which 48 cases had pleural sliding signs at the access site, and 47 patients successfully completed the examination; 3 cases without pleural sliding signs at the access site failed to complete thoracoscopy. In 21 cases, the fluid sonolucent area was selected as the access site, and all of them successfully completed thoracoscopy. CONCLUSION: Medical thoracoscopy is one of the methods to confirm the diagnosis in patients with pleural disease with small amounts or without pleural effusion. The application of thoracic ultrasound before medical thoracoscopy can be used for the selection of the access site. It is possible to replace pneumothorax induction before medical thoracoscopy.

Joint application of metagenomic next-generation sequencing and histopathological examination for the diagnosis of pulmonary infectious disease.

IMPORTANCE: The diagnosis of some pulmonary infectious diseases and their pathogens is very difficult. A more precise diagnosis of pulmonary infectious diseases can help clinicians use proper antibiotics as well as reduce the development of drug-resistant bacteria. In this study, we performed both mNGS and pathology on lung puncture biopsy tissue from patients and found that combined mNGS and histopathology testing was significantly more effective than histopathology testing alone in detecting infectious diseases and identifying infectious diseases. In addition, the combined approach improves the detection rate of pathogenic microorganisms in infectious diseases and can be used to guide precision clinical treatment.

Powerful-IoU: More straightforward and faster bounding box regression loss with a nonmonotonic focusing mechanism.

Bounding box regression (BBR) is one of the core tasks in object detection, and the BBR loss function significantly impacts its performance. However, we have observed that existing IoU-based loss functions suffer from unreasonable penalty factors, leading to anchor boxes expanding during regression and significantly slowing down convergence. To address this issue, we intensively analyzed the reasons for anchor box enlargement. In response, we propose a Powerful-IoU (PIoU) loss function, which combines a target size-adaptive penalty factor and a gradient-adjusting function based on anchor box quality. The PIoU loss guides anchor boxes to regress along efficient paths, resulting in faster convergence than existing IoU-based losses. Additionally, we investigate the focusing mechanism and introduce a non-monotonic attention layer that was combined with PIoU to obtain a new loss function PIoU v2. PIoU v2 loss enhances the capability to focus on anchor boxes of medium quality. By incorporating PIoU v2 into popular object detectors such as YOLOv8 and DINO, we achieved an increase in average precision (AP) and improved performance compared to their original loss functions on the MS COCO and PASCAL VOC datasets, thus validating the effectiveness of our proposed improvement strategies.

Cost-effectiveness of first-line immunotherapy for advanced non-small cell lung cancer with different PD-L1 expression levels: A comprehensive overview.

BACKGROUND: Immunotherapies can substantially improve treatment efficacy, despite their high cost. A comprehensive overview of the cost-effectiveness analysis (CEA) of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer based on different tumor proportion scores (TPSs) was conducted. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and NHS Economic Evaluation databases were searched from their inception until August 24, 2022. Data relevant to the CEA results were recorded, and quality assessments conducted based on the Quality of Health Economic Studies (QHES) process. FINDINGS: Fifty-one original studies from seven countries were included. The mean QHES score was 77.0 (range: 53-95). Twenty-seven studies were classified as high-quality, and the rest as fair quality. Pembrolizumab, nivolumab, ipilimumab, atezolizumab, camrelizumab, cemiplimab, sintilimab, tislelizumab, and durvalumab were identified using three TPS categories. While nivolumab plus ipilimumab and pembrolizumab plus chemotherapy were unlikely to be cost-effective in China, the results for the US were uncertain. Atezolizumab combinations were not cost-effective in China or the US, and tislelizumab and sintilimab were cost-effective in China. For TPSs ≥ 50%, the pembrolizumab monotherapy could be cost-effective in some developed countries. Cemiplimab was more cost-effective than chemotherapy, pembrolizumab, and atezolizumab in the US. For TPSs ≥ 1%, the cost-effectiveness of pembrolizumab was controversial due to the different willingness-to-pay thresholds. CONCLUSIONS: None of the atezolizumab combination regimens were found to be cost-effective in any perspective of evaluations. Camrelizumab, tislelizumab, and sintilimab have lower ICERs compared to atezolizumab, pembrolizumab, and nivolumab in China. Cemiplimab may be a more affordable alternative to pembrolizumab or atezolizumab. However, it remains unclear which ICIs are the best choices for each country. Future CEAs are required to select comprehensive regimens alongside randomized trials and real-world studies to help verify the economics of ICIs in specific decision-making settings.

Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer.

Phospholipase C epsilon 1 (PLCE1) is a well-established susceptibility gene for esophageal squamous cell carcinoma (ESCC). Identification of the underlying mechanism(s) regulated by PLCE1 could lead to a better understanding of ESCC tumorigenesis. In this study, we found that PLCE1 enhances tumor progression by regulating the replicative helicase MCM7 via two pathways. PLCE1 activated PKCα-mediated phosphorylation of E2F1, which led to the transcriptional activation of MCM7 and miR-106b-5p. The increased expression of miR-106b-5p, located in intron 13 of MCM7, suppressed autophagy and apoptosis by targeting Beclin-1 and RBL2, respectively. Moreover, MCM7 cooperated with the miR-106b-25 cluster to promote PLCE1-dependent cell-cycle progression both in vivo and in vitro. In addition, PLCE1 potentiated the phosphorylation of MCM7 at six threonine residues by the atypical kinase RIOK2, which promoted MCM complex assembly, chromatin loading, and cell-cycle progression. Inhibition of PLCE1 or RIOK2 hampered MCM7-mediated DNA replication, resulting in G1-S arrest. Furthermore, MCM7 overexpression in ESCC correlated with poor patient survival. Overall, these findings provide insights into the role of PLCE1 as an oncogenic regulator, a promising prognostic biomarker, and a potential therapeutic target in ESCC. SIGNIFICANCE: PLCE1 promotes tumor progression in ESCC by activating PKCα-mediated phosphorylation of E2F1 to upregulate MCM7 and miR-106b-5p expression and by potentiating MCM7 phosphorylation by RIOK2.

Tae-miR397 Negatively Regulates Wheat Resistance to Blumeria graminis.

MicroRNA (miRNA) plays a crucial role in the interactions between plants and pathogens, and identifying disease-related miRNAs could help us understand the mechanisms underlying plant disease pathogenesis and breed resistant varieties. However, the role of miRNA in wheat defense responses remains largely unexplored. The miR397 family is highly conserved in plants and involved in plant development and defense response. Therefore, the purpose of this study was to investigate the function of tae-miR397 in wheat resistance to powdery mildew. The expression pattern analysis revealed that tae-miR397 expression was higher in young leaves than in other tissues and was significantly decreased in wheat Bainong207 leaves after Blumeria graminis (Bgt) infection and chitin treatment. Additionally, the expression of tae-miR397 was significantly down-regulated by salicylic acid and induced under jasmonate treatment. The overexpression of tae-miR397 in common wheat Bainong207 enhanced the wheat's susceptibility to powdery mildew in the seedling and adult stages. The rate of Bgt spore germination and mycelial growth in transgenic wheat plants overexpressing tae-miR397 was faster than in the untransformed wild-type plants. The target gene of tae-miR397 was predicted to be a wound-induced protein (Tae-WIP), and the function was investigated. We demonstrated that silencing of Tae-WIP via barley-stripe-mosaic-virus-induced gene silencing enhanced wheat's susceptibility to powdery mildew. qRT-PCR indicated that tae-miR397 regulated wheat immunity by controlling pathogenesis-related gene expressions. Moreover, the transgenic plants overexpressing tae-miR397 exhibited more tillers than the wild-type plants. This work suggests that tae-miR397 is a negative regulator of resistance against powdery mildew and has great potential for breeding disease-resistant cultivars.

Studying the Interaction between Bendamustine and DNA Molecule with SERS Based on AuNPs/ZnCl2/NpAA Solid-State Substrate.

Bendamustine (BENDA) is a bifunctional alkylating agent with alkylating and purinergic antitumor activity, which exerts its anticancer effects by direct binding to DNA, but the detailed mechanism of BENDA-DNA interaction is poorly understood. In this paper, the interaction properties of the anticancer drug BENDA with calf thymus DNA (ctDNA) were systematically investigated based on surface-enhanced Raman spectroscopy (SERS) technique mainly using a novel homemade AuNPs/ZnCl2/NpAA (NpAA: nano porous anodic alumina) solid-state substrate and combined with ultraviolet-visible spectroscopy and molecular docking simulation to reveal the mechanism of their interactions. We experimentally compared and studied the SERS spectra of ctDNA, BENDA, and BENDA-ctDNA complexes with different molar concentrations (1:1, 2:1, 3:1), and summarized their important characteristic peak positions, their peak position differences, and hyperchromic/hypochromic effects. The results showed that the binding modes include covalent binding and hydrogen bonding, and the binding site of BENDA to DNA molecules is mainly the N7 atom of G base. The results of this study help to understand and elucidate the mechanism of BENDA at the single-molecule level, and provide guidance for the further development of effective new drugs with low toxicity and side effects.

Inhibiting zero-order light of a spatial light modulator with voltage optimization.

The crucial zero-order light due to the pixelation effect of spatial light modulator (SLM) has been a serious issue in the field of light modulation, especially in applications with a high numerical aperture optical system. In this investigation, we report that by properly adjusting the high-level and low-level pixel voltages of an SLM, the zero-order light caused by the pixelation effect of an SLM can be significantly eliminated. The method is further validated under an inverted fluorescence microscope. The experimental results show that the zero-order light can be inhibited up to 91.3%, accompanied by an improvement of the modulation efficiency from 77.5% to 92.6%.

Multi-Focal Laser Direct Writing through Spatial Light Modulation Guided by Scalable Vector Graphics.

Multi-focal laser direct writing (LDW) based on phase-only spatial light modulation (SLM) can realize flexible and parallel nanofabrication with high-throughput potential. In this investigation, a novel approach of combining two-photon absorption, SLM, and vector path-guided by scalable vector graphics (SVGs), termed SVG-guided SLM LDW, was developed and preliminarily tested for fast, flexible, and parallel nanofabrication. Three laser focuses were independently controlled with different paths, which were optimized according to the SVG to improve fabrication and promote time efficiency. The minimum structure width could be as low as 81 nm. Accompanied by a translation stage, a carp structure of 18.10 µm × 24.56 µm was fabricated. This method shows the possibility of developing LDW techniques toward fully electrical systems, and provides a potential way to efficiently engrave complex structures on nanoscales.

Chiral Adaptive Induction of an Achiral Cucurbit[8]uril-Based Supramolecular Organic Framework by Dipeptides in Water.

Chiral induction by natural biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we present the synthesis and characterization of an achiral supramolecular organic framework (SOF-1) constructed from cucurbit[8]uril (CB[8]) and hexaphenylbenzene (HPB) derivative (1) in water. Due to the propeller-like rotational chiral conformation of HPB units and the specific recognition properties of CB[8], SOF-1 demonstrates chiral adaptive induction in water when interacting with the N-terminal Trp-/Phe-containing dipeptides including L-TrpX and L-PheX (X is an amino acid residue), respectively, exhibiting contrasting circular dichroism (CD) and circularly polarized luminescence (CPL) spectra. Consequently, SOF-1 has been developed as a supramolecular host and chiroptical sensor capable of recognizing and distinguishing the sequence-opposite Trp-/Phe-containing dipeptide pairs including L-TrpX/L-XTrp and L-PheX/L-XPhe based on the sequence-selective CD responses.

Characterization of anoikis-based molecular heterogeneity in pancreatic cancer and pancreatic neuroendocrine tumor and its association with tumor immune microenvironment and metabolic remodeling.

Background: Accumulating evidence suggests that anoikis plays a crucial role in the onset and progression of pancreatic cancer (PC) and pancreatic neuroendocrine tumors (PNETs); nevertheless, the prognostic value and molecular characteristics of anoikis in cancers are yet to be determined. Materials and methods: We gathered and collated the multi-omics data of several human malignancies using the TCGA pan-cancer cohorts. We thoroughly investigated the genomics and transcriptomics features of anoikis in pan-cancer. We then categorized a total of 930 patients with PC and 226 patients with PNETs into distinct clusters based on the anoikis scores computed through single-sample gene set enrichment analysis. We then delved deeper into the variations in drug sensitivity and immunological microenvironment between the various clusters. We constructed and validated a prognostic model founded on anoikis-related genes (ARGs). Finally, we conducted PCR experiments to explore and verify the expression levels of the model genes. Results: Initially, we identified 40 differentially expressed anoikis-related genes (DE-ARGs) between pancreatic cancer (PC) and adjacent normal tissues based on the TCGA, GSE28735, and GSE62452 datasets. We systematically explored the pan-cancer landscape of DE-ARGs. Most DE-ARGs also displayed differential expression trends in various tumors, which were strongly linked to favorable or unfavorable prognoses of patients with cancer, especially PC. Cluster analysis successfully identified three anoikis-associated subtypes for PC patients and two anoikis-associated subtypes for PNETs patients. The C1 subtype of PC patients showed a higher anoikis score, poorer prognosis, elevated expression of oncogenes, and lower level of immune cell infiltration, whereas the C2 subtype of PC patients had the exact opposite characteristics. We developed and validated a novel and accurate prognostic model for PC patients based on the expression traits of 13 DE-ARGs. In both training and test cohorts, the low-risk subpopulations had significantly longer overall survival than the high-risk subpopulations. Dysregulation of the tumor immune microenvironment could be responsible for the differences in clinical outcomes between low- and high-risk groups. Conclusions: These findings provide fresh insights into the significance of anoikis in PC and PNETs. The identification of subtypes and construction of models have accelerated the progress of precision oncology.

Flow Cytometry with Anti-Diffraction Light Sheet (ADLS) by Spatial Light Modulation.

Flow cytometry is a widespread and powerful technique whose resolution is determined by its capacity to accurately distinguish fluorescently positive populations from negative ones. However, most informative results are discarded while performing the measurements of conventional flow cytometry, e.g., the cell size, shape, morphology, and distribution or location of labeled exosomes within the unpurified biological samples. Herein, we propose a novel approach using an anti-diffraction light sheet with anisotroic feature to excite fluorescent tags. Constituted by an anti-diffraction Bessel-Gaussian beam array, the light sheet is 12 µm wide, 12 µm high, and has a thickness of ~0.8 µm. The intensity profile of the excited fluorescent signal can, therefore, reflect the size and allow samples in the range from O (100 nm) to 10 µm (e.g., blood cells) to be transported via hydrodynamic focusing in a microfluidic chip. The sampling rate is 500 kHz, which provides a capability of high throughput without sacrificing the spatial resolution. Consequently, the proposed anti-diffraction light sheet flow cytometry (ADLSFC) can obtain more informative results than the conventional methodologies, and is able to provide multiple characteristics (e.g., the size and distribution of fluorescent signal) helping to distinguish the target samples from the complex backgrounds.

High-Durability Photothermal Slippery Surfaces for Droplet Manipulation Based on Ultraviolet Lithography.

Photothermal slippery surface has broad applications in many research fields for noncontacting, loss-free, and flexible droplet manipulation capability. In this work, with specific morphologic parameters and modified base materials doped by Fe3O4, a high-durability photothermal slippery surface (HD-PTSS) was proposed and implemented based on ultraviolet (UV) lithography to achieve repeatability of more than 600 cycles. The instantaneous response time and transport speed of HD-PTSS were related to near-infrared ray (NIR) powers and droplet volume. Meanwhile, the durability was closely related to the morphology of HD-PTSS, which impacts the recovering of a lubricant layer. The droplet manipulation mechanism of HD-PTSS was discussed in depth, and the Marangoni effect was found to be the key factor for the durability of HD-PTSS.

Transition Routes of Electrokinetic Flow in a Divergent Microchannel with Bending Walls.

Electrokinetic flow can be generated as a highly coupled phenomenon among velocity fields, electric conductivity fields, and electric fields. It can exhibit different responses to AC electric fields in different frequency regimes, according to different instability/receptivity mechanisms. In this investigation, by both flow visualization and single-point laser-induced fluorescence (LIF) method, the response of AC electrokinetic flow and the transition routes towards chaos and turbulence have been experimentally investigated. It is found, when the AC frequency ff>30 Hz, the interface responds at both the neutral frequency of the basic flow and the AC frequency. However, when ff≥30 Hz, the interface responds only at the neutral frequency of the basic flow. Both periodic doubling and subcritical bifurcations have been observed in the transition of AC electrokinetic flow. We hope the current investigation can promote our current understanding of the ultrafast transition process of electrokinetic flow from laminar state to turbulence.

A novel fire smoke removal technology using electric agglomeration: The concept, experimental verification and mechanisms.

Electric agglomeration technology is effective in removing particulate matter from the environment and has been widely used in the field of dust removal. For the first time, this technology is applied to the field of fire smoke removal at lab scale. By varying applied electric potential and initial concentration of smoke, the removal characteristics and mechanisms during the electric agglomeration process are systematically studied. The results show that when the applied electric potential is higher than 4 kV, the smoke transmittance increases from 4% to 90% in just 10 s, and the threshold for people safe escape can be reached in only 5 s. Three main mechanisms involved in the process of smoke removal using electric agglomeration are proposed. In addition to the conventional Coulomb agglomeration of charged particles, the turbulence-enhanced agglomeration induced by ionic wind and dipole chainization at the grounded plate are also observed. This study demonstrates the feasibility and potential of electric agglomeration technology to remove fire smoke.

Onset of Nonlinear Electroosmotic Flow under an AC Electric Field.

Nonlinearity of electroosmotic flows (EOFs) is ubiquitous and plays a crucial role in ion transport, specimen mixing, electrochemistry reaction, and electric energy storage and utilization. When and how the transition from a linear regime to a nonlinear one occurs is essential for understanding, prohibiting, or utilizing nonlinear EOF. However, due to the lack of reliable experimental instruments with high spatial and temporal resolutions, the investigation of the onset of nonlinear EOF still remains in theory. Herein, we experimentally studied the velocity fluctuations of EOFs driven by an alternating current (AC) electric field via ultrasensitive fluorescent blinking tricks. The linear and nonlinear AC EOFs are successfully identified from both the time trace and energy spectra of velocity fluctuations. The transitional electric field (EA,C) is determined by both the convection velocity (U) and AC frequency (ff) as EA,C ∼ ff0.48-0.027U. We hope the current investigation could be essential in the development of both theory and applications of nonlinear EOFs.