Novel Diagnostic Biomarker BST2 Identified by Integrated Transcriptomics Promotes the Development of Endometriosis via the TNF-α/NF-κB Signaling Pathway.

Endometriosis (EMS) is a common gynecological condition with apparent heterogeneity, lack of diagnostic markers, and unclear pathogenesis. A series of bioinformatics methods were employed to explore EMS's pathological mechanisms and potential biomarkers by analyzing the combined datasets of EMS (GSE7305, GSE7307, GSE58198, E-MTAB-694), which included 34 normal, 127 eutopic, and 46 ectopic endometrium samples. Then, wet-laboratory experiments (including Western blot, qRT-PCR, and Immunohistochemistry, Immunofluorescence, CCK-8, EdU, Wound healing, Transwell, and Adhesion assays) were applied to examine the biomarkers' expression and function in primary endometrial stromal cells. Bioinformatic analysis indicated that the core pathogenesis of EMS was dysregulated immune-inflammation and tissue remolding processes. Among the upregulated DEGs, BST2 was screened as a potential diagnostic biomarker in EMS, which associated with the revised American Fertility Society (r-AFS) stage and immune-inflammation processes of EMS. Moreover, BST2's overexpression was affirmed in the RNA and protein levels in EMS tissues. In vitro experiments demonstrated that TNF-α promoted the expression of BST2 in ESCs. And BST2 knockdown inhibited migration, invasion, adhesion, and inflammation except for the proliferation of ESCs, probably via the TNF-α/NF-κB pathway. Through a combination of wet and dry studies, we concluded that the core pathogenesis of endometriosis was dysregulated immune-inflammation and tissue remolding, and BST2 might be a potential diagnostic and therapeutic target in endometriosis.

Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis.

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting of acid-degradable copper hydride (CuH) nanoparticles was developed via a microfluidic synthesis. After coating with tumor-targeting hyaluronic acid (HA), the nanoplatform denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. Cu+ can induce apoptosis by relying on Fenton-like reactions and lead to cuproptosis by causing mitochondrial protein aggregation. Besides, the existence of H2 can enhance both cell death types by causing mitochondrial dysfunction and intracellular redox homeostatic disorders. In vivo experimental results further exhibit the desirable potential of HCP for killing tumor cells and inhibiting lung metastases, which will broaden the horizons of designing copper-based materials triggering apoptosis and cuproptosis for better antitumor efficacy.

Self-Metallized Whole Cell Vaccines Prepared by Microfluidics for Bioorthogonally Catalyzed Antitumor Immunotherapy.

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.

Self-generating Gold Nanocatalysts in Autologous Tumor Cells for Targeted Catalytic Immunotherapy.

Employing tumor whole cells for tumor immunotherapy is a promising tumor therapy proposed in the early stage, but its therapeutic efficacy is weakened by the methods of eliminating pathogenicity and the mass ratio of the effective antigen carried by itself. Here, by adding gold ion to live cancer cells in the microfluidic droplets, w e obtain dead tumor whole cells with NIR-controlled catalytic ability whose pathogenicity is removed while plenary tumor antigens, major structure, and homing ability are reserved. The engineered tumor cell (Cell-Au) with the addition of prodrug provides 1 O2 in an O2 -free Russell mechanism, which serves better in a hypoxic tumor microenvironment. This tumor whole-cell catalytic vaccine (TWCV) promotes the activation of dendritic cells and the transformation of macrophages into tumor suppressor phenotype. In 4T1 tumor-bearing mice, the Cell-Au-based vaccine supports the polarization of cytotoxicity T cells, resulting in tumor eradication and long-term animal survival. Compared with antigen vaccines or adoptive cell therapy which takes months to obtain, this TWCV can be prepared in just a few days with satisfactory immune activation and tumor therapeutic efficacy, which provides an alternative way for the preparation of personalized tumor vaccines across tumor types and gives immunotherapy a new path. This article is protected by copyright. All rights reserved.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Keto-Adamantane-Based Macrocycle Crystalline Supramolecular Assemblies Showing Selective Vapochromism to Tetrahydrofuran.

Here, we report the synthesis of adamantane-based macrocycle 2 by combining adamantane building blocks with π-donor 1,3-dimethoxy-benzene units. An unpredictable keto-adamantane-based macrocycle 3 was obtained by the oxidation of 2 using DDQ as an oxidant. Moreover, a new type of macrocyclic molecule-based CT cocrystal was prepared through exo-wall CT interactions between 3 and DDQ. The cocrystal material showed selective vapochromism behavior towards THF, specifically, among nine volatile organic solvents commonly used in the laboratory. Powder X-ray diffraction; UV-Vis diffuse reflectance spectroscopy; 1H NMR; and single crystal X-ray diffraction analyses revealed that color changes are attributed to the vapor-triggered decomplexation of cocrystals.

Pulmonary rehabilitation protocols in urgent lung transplantation patients.

BACKGROUND: Prolonged invasive respiratory support and extracorporeal membrane oxygenation (ECMO) in patients requiring urgent lung transplantation (ULTx) present significant challenges to clinical practice due to severe underlying diseases and complex conditions. The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center. METHODS: A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation (IMV) and ECMO between January 2018 and January 2023. Data were retrieved from electronic medical records at our lung transplant center. RESULTS: Fourteen patients (mean age 57.43±10.97 years; 12 males, 2 females) underwent ULTx with bridging ECMO and IMV. The mean body mass index was 23.94±3.33 kg/m², and the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.50±3.96. The Nutritional Risk Screening 2002 (NRS 2002) scores were ≥3. ULTx was performed after an 8.5-day waiting period (interquartile interval [IQR] 5.0-26.5 d). Following the surgeries, the average lengths of ECMO and IMV were 1.0 (IQR 1.0-2.0) d and 5.0 (IQR 3.0-7.3) d, respectively. The total length of hospital stay was 60.1±30.8 d, with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d. Two patients died within 30 d after ULTx, with a 30-day survival rate of 85.71%. CONCLUSION: Patients receiving ULTx showed an acceptable short-term survival rate, validating the practicality and safety of the treatment protocols implemented in our center.

Developing and validating a prediction model of live birth in patients with moderate-to-severe intrauterine adhesions: a new approach with endometrial morphology measurement by 3D transvaginal ultrasound.

Background: There is no reliable method to predict the live birth rate among patients with moderate-to-severe intrauterine adhesions (IUA) after second-look hysteroscopy. Therefore, we aimed to construct a practical prediction model mainly based on the features of 3D transvaginal ultrasound (3D-TVUS). and other clinical characteristics. Methods: From January 2018 to February 2020, a total of 870 IUA patients with fertility requirements were retrospectively enrolled based on the same method. First, the predictors were screened by logistic regression analysis. A nomogram was constructed based on the screened predictive factors in the derivation cohort. Next, receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA) were used to assess the predictive accuracy and discriminability of the model. Finally, correlation analysis was performed to analyze the correlation between the results of 3D-TVUS and second-look hysteroscopy. Results: A total of 558 (64.14%) participants had live births. Age, endometrial thickness, assisted reproductive technology, a homogeneous endometrial echo, a lower segment of scar contraction, and upper segmentation of the endometrial absence were included in the model. The predictive model showed good predictive performance in the derivation cohort (area under the curve, 0.837) and validation cohort (0.857). DCA demonstrated its clinical utility. A homogeneous endometrial echo was related to no segmentation of scar contraction (r=0.219; P<0.001) or no segmentation of the endometrial absence (r=0.226; P<0.001). Thicker endometrium was associated with no segmentation of the endometrial absence (r=-0.145; P=0.007). Conclusions: The proposed method can effectively predict live birth. 3D-TVUS should be an important means for evaluating the endometrium of moderate-to-severe patients with IUA preparing for pregnancy after operation.

Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption.

INTRODUCTION: The continuous emergence and rapid spread of multidrug-resistant bacteria have accelerated the demand for the discovery of alternative antibiotics. Natural plants contain a variety of antibacterial components, which is an important source for the discovery of antimicrobial agents. OBJECTIVE: To explore the antimicrobial activities and related mechanisms of two lavandulylated flavonoids, sophoraflavanone G and kurarinone in Sophora flavescens against methicillin-resistant Staphylococcus aureus. METHODS: The effects of sophoraflavanone G and kurarinone on methicillin-resistant Staphylococcus aureus were comprehensively investigated by a combination of proteomics and metabolomics studies. Bacterial morphology was observed by scanning electron microscopy. Membrane fluidity, membrane potential, and membrane integrity were determined using the fluorescent probes Laurdan, DiSC3(5), and propidium iodide, respectively. Adenosine triphosphate and reactive oxygen species levels were determined using the adenosine triphosphate kit and reactive oxygen species kit, respectively. The affinity activity of sophoraflavanone G to the cell membrane was determined by isothermal titration calorimetry assays. RESULTS: Sophoraflavanone G and kurarinone showed significant antibacterial activity and anti-multidrug resistance properties. Mechanistic studies mainly showed that they could target the bacterial membrane and cause the destruction of the membrane integrity and biosynthesis. They could inhibit cell wall synthesis, induce hydrolysis and prevent bacteria from synthesizing biofilms. In addition, they can interfere with the energy metabolism of methicillin-resistant Staphylococcus aureus and disrupt the normal physiological activities of the bacteria. In vivo studies have shown that they can significantly improve wound infection and promote wound healing. CONCLUSION: Kurarinone and sophoraflavanone G showed promising antimicrobial properties against methicillin-resistant Staphylococcus aureus, suggesting that they may be potential candidates for the development of new antibiotic agents against multidrug-resistant bacteria.

Methionine restriction attenuates the migration and invasion of gastric cancer cells by inhibiting nuclear p65 translocation through TRIM47.

The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for in vivo experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation in vivo compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells.

Core-dependent post-translational modifications guide the biosynthesis of a new class of hypermodified peptides.

The ribosomally synthesized and post-translationally modified peptide (RiPPs) class of natural products has undergone significant expansion due to the rapid growth in genome sequencing data. Using a bioinformatics approach, we identify the dehydrazoles, a novel class of hypermodified RiPPs that contain both side chain dehydration of Ser residues, and backbone heterocyclization at Ser, Thr, and Cys residues to the corresponding azol(in)es. Structure elucidation of the hypermodified peptide carnazolamide, a representative class member, shows that 18 post-translational modifications are installed by just five enzymes. Complete biosynthetic reconstitution demonstrates that dehydration is carried out by an unusual DUF4135 dehydration domain fused to a zinc-independent cyclase domain (CcaM). We demonstrate that CcaM only modifies Ser residues that precede an azole in the core peptide. As heterocyclization removes the carbonyl following the Ser residue, CcaM likely catalyzes dehydration without generating an enolate intermediate. Additionally, CcaM does not require the leader peptide, and this core-dependence effectively sets the order for the biosynthetic reactions. Biophysical studies demonstrate direct binding of azoles to CcaM consistent with this azole moiety-dependent dehydration. Bioinformatic analysis reveals more than 50 related biosynthetic gene clusters that contain additional catalysts that may produce structurally diverse scaffolds.

Advances in Polyoxometalates as Electron Mediators for Photocatalytic Dye Degradation.

The increasing concerns over the environment and the growing demand for sustainable water treatment technologies have sparked substantial interest in the field of photocatalytic dye removal. Polyoxometalates (POMs), known for their intricate metal-oxygen anion clusters, have received considerable attention due to their versatile structures, compositions, and efficient facilitation of photo-induced electron transfers. This paper provides an overview of the ongoing research progress in the realm of photocatalytic dye degradation utilizing POMs and their derivatives. The details encompass the compositions of catalysts, catalytic efficacy, and light absorption propensities, and the photocatalytic mechanisms inherent to POM-based materials for dye degradation are exhaustively expounded upon. This review not only contributes to a better understanding of the potential of POM-based materials in photocatalytic dye degradation, but also presents the advancements and future prospects in this domain of environmental remediation.

Decarbonization potentials of the embodied energy use and operational process in buildings: A review from the life-cycle perspective.

Accounting for one third of global energy-related carbon emissions, the construction and operation of buildings are crucial for mitigating climate change. Decarbonization potentials of embodied and operational energy use in buildings are worth exploring from a life-cycle perspective. This paper focuses on the individual building level and collects the latest cases, to offer a comprehensive and timely understanding of the assessment and reduction of building life cycle carbon emissions (LCCEs). As for the collected cases, the operational process accounts for the largest share of building LCCEs, averaging 67%, followed by the production and construction phase, averaging 31%. Carbon emissions from the demolition process are relatively low, averaging 2%. The most commonly used method for assessing LCCEs is process-based, combining the activity level and carbon emission factors. Advanced technologies such as building information modelling and building performance simulation have been employed in recent years to assess embodied and operational carbon emissions effectively. Different approaches are proposed for the decarbonization of each stage in the building life cycle. In the production stage, the effective approaches could be optimizing the building structure, improving the material performance, and using bio-based materials, etc. Prefabrication technology is helpful to decarbonize the construction process. Energy conservation and electrification, renewable energy integration, and smart energy management can effectively reduce the building's operational carbon emissions. Beyond the life cycle, recycling waste materials is proven to have great environmental benefits. Further studies are suggested to trade off the embodied and operational carbon, to fully explore building life-cycle decarbonization potentials.

Pharmacotherapy of urethral stricture.

ABSTRACT: Urethral stricture is characterized by the chronic formation of fibrous tissue, leading to the narrowing of the urethral lumen. Despite the availability of various endoscopic treatments, the recurrence of urethral strictures remains a common challenge. Postsurgery pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence rates. Although drugs cannot replace surgery, they can be used as adjuvant therapies to improve outcomes. In this regard, many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral stricture. Ongoing studies have obtained substantial progress in treating urethral strictures, highlighting the potential for improved drug effectiveness through appropriate clinical delivery methods. Therefore, this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

Giant Cavity Macrocycle: Synthesis, Structure, and Its Complexation with Pagoda[5]arene.

A novel stretched hexagon structure naphthalene diimides-extended-pillar[6]arene 1 with a giant cavity size of 18.769 Å in width and 17.109 Å in height is reported. 1 exhibits highly selective binding of pagoda[5]arene compared to pillar[5]arene and prism[5]arene. Size matching and charge transfer interactions play a key role in the formation of the ring-in-ring stable complex.

Influences of dexmedetomidine on stress responses and postoperative cognitive and coagulation functions in patients undergoing radical gastrectomy under general anesthesia.

BACKGROUND: Radical gastrectomy (RG) is commonly used in the treatment of patients with gastric cancer (GC), but this procedure may lead to stress responses, postoperative cognitive dysfunction, and blood coagulation abnormalities in patients. AIM: To investigate the influences of dexmedetomidine (DEX) on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia (GA). METHODS: One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed. Of these, 50 patients had received conventional anesthesia intervention [control group (CG)] and 52 patients had received DEX in addition to routine anesthesia intervention [observation group (OG)]. Inflammatory factor (IFs; tumor necrosis factor-α, TNF-α; interleukin-6, IL-6), stress responses (cortisol, Cor; adrenocorticotropic hormone, ACTH), cognitive function (CF; Mini-Mental State Examination, MMSE), neurological function (neuron-specific enolase, NSE; S100 calcium-binding protein B, S100B), and coagulation function (prothrombin time, PT; thromboxane B2, TXB2; fibrinogen, FIB) were compared between the two groups before surgery (T0), as well as at 6 h (T1) and 24 h (T2) after surgery. RESULTS: Compared with T0, TNF-α, IL-6, Cor, ACTH, NSE, S100B, PT, TXB2, and FIB showed a significant increase in both groups at T1 and T2, but with even lower levels in OG vs CG. Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0, but the MMSE score was notably higher in OG compared with CG. CONCLUSION: In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA, DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.

SAW Filters on LiNbO3/SiC Heterostructure for 5G n77 and n78 Band Applications.

The 5G communication system has experienced a substantial expansion of the spectrum, which poses higher requirements to radio frequency (RF) filters in enhancing their operating frequencies and bandwidths. To this end, this work focused on solving the filtering scheme for challenging 5G n77 and n78 bands and successfully implemented the corresponding spurious-free surface acoustic wave (SAW) filters exploiting large-coupling shear horizontal (SH) modes based on X-cut LiNbO3 (LN)/silicon carbide (SiC) heterostructure. Here, we initially investigated the suppression methods for spurious modes theoretically and experimentally and summarized an effective normalized LN thickness ( [Formula: see text] range of 0.15-0.30 for mitigating Rayleigh modes and higher order modes, as well as tilted interdigital transducers (IDT) by about 24° for eliminating transverse modes. Resonators with wavelengths ( λ) from 0.95 to [Formula: see text] were also fabricated, showing a scalable resonance from 2.48 to 4.21 GHz without any in-band ripple. Two filters completely meeting 5G n77 and n78 full bands were finally constructed, showing center frequencies ( fc) of 3763 and 3560 MHz, 3-dB fractional bandwidths (FBW) of 24.8% and 15.6%, and out-of-band (OoB) rejections of 18.7 and 28.1 dB, respectively. This work reveals that X-LN/SiC heterostructure is a promising underpinning material for SAW filters in 5G commercial applications.

Exploring the protective effect of Sangggua Drink against type 2 diabetes mellitus in db/db mice using a network pharmacological approach and experimental validation.

Sanggua Drink (SGD) is an experienced formula for clinical treatment of type 2 diabetes mellitus (T2DM). Network pharmacology and experiments were combined to explore the potential mechanism of action of SGD on T2DM. The material basis and action mechanism of SGD were investigated to reveal the active components of SGD, potential target prediction was conducted from TargetNet, PharmMapper; Cytoscape was used to construct PPI network and component-target-pathway (C-T-P) network diagram to interpret biological processes and enrich action pathways. 54 compounds and 41 key target proteins were screened, and a total of 98 signaling pathways were obtained. In vivo experiments, the levels of p-AMPK (P < 0.01), p-ACC and p-AKT were significantly increased in the mice with SGD intervention compared to the db/db mice, while level of FOXO1 were decreased. The results suggested that SGD might improve insulin resistance and glucose metabolism in T2DM mice by activating the AMPK/Akt signaling pathway.

Application effect of gastrointestinal bundle nursing on the protection of gastrointestinal function in patients with gastric cancer.

Evidence-based nursing practice was used to formulate the enhanced recovery surgery bundle nursing strategy and apply it to patients with gastric cancer, to explore its safety, effectiveness and feasibility in perioperative gastrointestinal function protection in patients with gastric cancer. Selected the clinical medical records of 100 gastric cancer patients treated in our hospital from June 2019 to June 2021 as the research objects, and divided them into the control group and the observation group with 50 cases in each group according to the random number table. Among them, the control group was given routine nursing measures for nursing intervention, and the observation group was given gastrointestinal enhanced recovery surgery cluster nursing on the basis of the control group. The differences in stress response, gastrointestinal function protection, negative emotions and pain scores of gastric cancer patients before and after nursing were compared between the 2 groups. The postoperative bowel sounds recovery time, first anal exhaust, and first defecation time in the observation group were lower than those in the control group, and the differences were statistically significant (P < .05). Before nursing, there was no significant difference in the scores of stress response changes between the 2 groups (P > .05). After nursing, heart rate (HR), mean arterial pressure (MAP), norepinephrine (NE), and epinephrine (E2) in the observation group were lower than those in the control group, and the difference was statistically significant (P < .05). The pain scores of the 2 groups were significantly improved at different time points, and the observation group was significantly less than the control group, and the difference was statistically significant (P < .05). Gastrointestinal enhanced recovery surgery bundle nursing can effectively improve the gastrointestinal function of patients with gastric cancer, improve the emotional response and stress response of patients, and has certain reference value for the nursing of patients with gastric cancer.

Binaphthyl-Based Chiral Macrocyclic Hosts for the Selective Recognition of Iodide Anions.

In this study, we explorethe synthesis of binaphthyl-based chiral macrocyclic hosts for the first time. They exhibited the selective recognition abilities of iodide anions which can be favored over those of other anions (AcO-, NO3-, ClO4-, HSO4-, Br-, PF6-, H2PO4-, BF4-, and CO3F3S-), as confirmed by UV-vis, HRMS, and 1H NMR spectroscopy experiments, as well as DFT calculations. Neutral aryl C-H···anion interactions play an important role in the formation complexes. The recognition process can be observed by the naked eye.