Monitoring Ammonium Polyphosphate (APP) Biodegradation by Acinetobacter nosocomialis D-3 Using DAPI.

Ammonium polyphosphate (APP), a pivotal constituent within environmentally friendly flame retardants, exhibits notable decomposition susceptibility and potentially engenders ecological peril. Consequently, monitoring the APP concentration to ensure product integrity and facilitate the efficacious management of wastewater from production processes is of great significance. A fluorescent assay was devised to swiftly discern APP utilizing 4',6'-diamino-2-phenylindole (DAPI). With increasing APP concentrations, DAPI undergoes intercalation within its structure, emitting pronounced fluorescence. Notably, the flame retardant JLS-PNA220-A, predominantly comprising APP, was employed as the test substrate. Establishing a linear relationship between fluorescence intensity (F-F0) and JLS-PNA220-A concentration yielded the equation y = 76.08x + 463.2 (R2 = 0.9992), with a LOD determined to be 0.853 mg/L. The method was used to assess the degradation capacity of APP-degrading bacteria. Strain D-3 was isolated, and subsequent analysis of its 16S DNA sequence classified it as belonging to the Acinetobacter genus. Acinetobacter nosocomialis D-3 demonstrated superior APP degradation capabilities under pH 7 at 37 °C, with degradation rates exceeding 85% over a four-day cultivation period. It underscores the sensitivity and efficacy of the proposed method for APP detection. Furthermore, Acinetobacter nosocomialis D-3 exhibits promising potential for remediation of residual APP through environmental biodegradation processes.

The relationship between the psychological resilience and post-traumatic growth of college students during the COVID-19 pandemic: a model of conditioned processes mediated by negative emotions and moderated by deliberate rumination.

BACKGROUND: The mental health of university students during the COVID-19 pandemic has attracted the attention of researchers. For the present study researchers constructed a mediation model to explore the relationship between psychological resilience and post-traumatic growth, the mediating role of negative emotions and the moderating role of deliberate rumination in students. METHODS: The Psychological Resilience Scale, Posttraumatic Growth Inventory, Depression-Anxiety-Stress Scale (DASS-21) and Event Related Rumination Inventory were used in a survey of 881 college students. The data were analyzed using SPSS 26.0 and the PROCESS plugin (version 3.3). RESULTS: (1) Psychological resilience is positively related with post-traumatic growth. Deliberate rumination is positively related to psychological resilience, posttraumatic growth, and negative emotions. Psychological resilience, post-traumatic growth and negative emotions are negatively related. (2) Negative emotions mediated the relationship between psychological resilience and post-traumatic growth. (3) Deliberate rumination plays a moderating role in psychological resilience affecting negative emotions. Deliberate rumination plays a moderating role in the extent to which psychological resilience influences PTG through negative emotions. CONCLUSIONS: Psychological resilience affects post-traumatic growth directly and also indirectly through negative emotions. With the increase of mental resilience, the level of negative emotion tended to decrease. When individuals are experiencing negative emotions, high levels of active rumination are more likely to promote post-traumatic growth. This study helps to explore the factors affecting the mental health of college students during the epidemic, thus providing guidance for appropriate mental health interventions.

A miniaturized mesoscope for the large-scale single-neuron-resolved imaging of neuronal activity in freely behaving mice.

Exploring the relationship between neuronal dynamics and ethologically relevant behaviour involves recording neuronal-population activity using technologies that are compatible with unrestricted animal behaviour. However, head-mounted microscopes that accommodate weight limits to allow for free animal behaviour typically compromise field of view, resolution or depth range, and are susceptible to movement-induced artefacts. Here we report a miniaturized head-mounted fluorescent mesoscope that we systematically optimized for calcium imaging at single-neuron resolution, for increased fields of view and depth of field, and for robustness against motion-generated artefacts. Weighing less than 2.5 g, the mesoscope enabled recordings of neuronal-population activity at up to 16 Hz, with 4 µm resolution over 300 µm depth-of-field across a field of view of 3.6 × 3.6 mm2 in the cortex of freely moving mice. We used the mesoscope to record large-scale neuronal-population activity in socially interacting mice during free exploration and during fear-conditioning experiments, and to investigate neurovascular coupling across multiple cortical regions.

Resiquimod-loaded cationic liposomes cure mice with peritoneal carcinomatosis and induce specific anti-tumor immunity.

Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), primarily due to incomplete cancer elimination. To enhance the standard of care for PC, we developed two cationic liposomal formulations aimed at localizing a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity to activate the immune system locally to specifically eradicate residual tumor cells. These formulations effectively extended R848 retention in the peritoneum by >10-fold, resulting in up to a 2-fold increase in interferon α (IFN-α) induction in the peritoneal fluid, without increasing the plasma levels. In a CT26 colon cancer model with peritoneal metastases, these liposomal R848 formulations, when combined with oxaliplatin (OXA)-an agent used in HIPEC that induces immunogenic cell death-increased tumor infiltration of effector immune cells, including DCs, CD4, and CD8 T cells. This led to the complete elimination of PC in 60-70% of the mice, while the control mice reached humane endpoints by 30 days. The cured mice developed specific antitumor immunity, as re-challenging them with the same tumor cells did not result in tumor establishment. However, inoculation with a different tumor line led to tumor development. Additionally, exposing CT26 tumor antigens to the splenocytes isolated from the cured mice induced the expansion of CD4 and CD8 T cells and the release of IFN-γ, demonstrating long-term immune memory to the specific tumor. The anti-tumor efficacy of these liposomal R848 formulations was mediated via CD8 T cells with different levels of involvement of CD4 and B cells, and the combination with an anti-PD-1 antibody achieved a cure rate of 90%.

Long-term intravital subcellular imaging with confocal scanning light-field microscopy.

Long-term observation of subcellular dynamics in living organisms is limited by background fluorescence originating from tissue scattering or dense labeling. Existing confocal approaches face an inevitable tradeoff among parallelization, resolution and phototoxicity. Here we present confocal scanning light-field microscopy (csLFM), which integrates axially elongated line-confocal illumination with the rolling shutter in scanning light-field microscopy (sLFM). csLFM enables high-fidelity, high-speed, three-dimensional (3D) imaging at near-diffraction-limit resolution with both optical sectioning and low phototoxicity. By simultaneous 3D excitation and detection, the excitation intensity can be reduced below 1 mW mm-2, with 15-fold higher signal-to-background ratio over sLFM. We imaged subcellular dynamics over 25,000 timeframes in optically challenging environments in different species, such as migrasome delivery in mouse spleen, retractosome generation in mouse liver and 3D voltage imaging in Drosophila. Moreover, csLFM facilitates high-fidelity, large-scale neural recording with reduced crosstalk, leading to high orientation selectivity to visual stimuli, similar to two-photon microscopy, which aids understanding of neural coding mechanisms.

Discovery of Selective Proteolysis-Targeting Chimera Degraders Targeting PTP1B as Long-Term Hypoglycemic Agents.

PTP1B, a promising target for insulin sensitizers in type 2 diabetes treatment, can be effectively degraded using proteolysis-targeting chimera (PROTAC). This approach offers potential for long-acting antidiabetic agents. We report potent bifunctional PROTACs targeting PTP1B through the E3 ubiquitin ligase cereblon. Western blot analysis showed significant PTP1B degradation by PROTACs at concentrations from 5 nM to 5 µM after 48 h. Evaluation of five highly potent PROTACs revealed compound 75 with a longer PEG linker (23 atoms), displaying remarkable degradation activity after 48 and 72 h, with DC50 values of 250 nM and 50 nM, respectively. Compound 75 induced selective degradation of PTP1B, requiring engagement with both the target protein and CRBN E3 ligase, in a ubiquitination and proteasome-dependent manner. It significantly reduced blood glucose AUC0-2h to 29% in an oral glucose tolerance test and activated the IRS-1/PI3K/Akt signaling pathway in HepG2 cells, showing promise for long-term antidiabetic therapy.

MnO2 and roflumilast-loaded probiotic membrane vesicles mitigate experimental colitis by synergistically augmenting cAMP in macrophage.

BACKGROUND: Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC. RESULTS: Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO2 were encapsulated in MVs (Rof&MnO2@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO2 boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO2 apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO2@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia-Shigella and elevating probiotic Akkermansia. CONCLUSIONS: A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO2 into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis.

Zero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy.

Computational super-resolution methods, including conventional analytical algorithms and deep learning models, have substantially improved optical microscopy. Among them, supervised deep neural networks have demonstrated outstanding performance, however, demanding abundant high-quality training data, which are laborious and even impractical to acquire due to the high dynamics of living cells. Here, we develop zero-shot deconvolution networks (ZS-DeconvNet) that instantly enhance the resolution of microscope images by more than 1.5-fold over the diffraction limit with 10-fold lower fluorescence than ordinary super-resolution imaging conditions, in an unsupervised manner without the need for either ground truths or additional data acquisition. We demonstrate the versatile applicability of ZS-DeconvNet on multiple imaging modalities, including total internal reflection fluorescence microscopy, three-dimensional wide-field microscopy, confocal microscopy, two-photon microscopy, lattice light-sheet microscopy, and multimodal structured illumination microscopy, which enables multi-color, long-term, super-resolution 2D/3D imaging of subcellular bioprocesses from mitotic single cells to multicellular embryos of mouse and C. elegans.

Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17.

Seven new phenol derivatives, subversins A-E (1-5), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (9-13) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds.

Effects of acupuncture at myofascial trigger points combined with sling exercise therapy on clinical recovery and cervical spine biomechanics in patients with cervical spondylotic radiculopathy.

OBJECTIVE: This research aimed to ascertain the effects of acupuncture at myofascial trigger points (MTrPs) in combination with sling exercise therapy (SET) on the clinical recovery and cervical spine biomechanics in patients with cervical spondylotic radiculopathy (CRS). METHODS: Eighty patients with CSR were divided into Group A and Group B. Group A was treated with acupuncture at MTrPs, and Group B was treated with acupuncture at MTrPs combined with SET. The cervical spine function, pain level, cervical spine biomechanics and the occurrence of complications were compared between the two groups before and after treatment. RESULTS: After treatment, the Japanese Orthopaedic Association scores, Clinical Assessment Scale for Cervical Spondylosis scores, cervical forward flexion angle, posterior extension angle, left lateral flexion angle, right lateral flexion angle, left lateral rotation angle, and right lateral rotation angle of the Group B were raised, and the Neck Disability index, Visual Analogue Scale scores, and Neck Pain Questionnaire scores were reduced versus those of the Group A. The difference in complication rates between the two groups was not of statistical significance. CONCLUSION: Acupuncture at MTrPs combined with SET promotes functional recovery of the cervical spine, reduces pain, and improves cervical spine biomechanics in patients with CRS.

Mn Single-Atom Nanozyme Functionalized 3D-Printed Bioceramic Scaffolds for Enhanced Antibacterial Activity and Bone Regeneration.

Infective bone defect is increasingly threatening human health. How to achieve the optimal antibacterial activity and regenerative repair of infective bone defect simultaneously is a huge challenge in clinic. Herein, this work reports a rational integration of Mn single-atom nanozyme into the 3D-printed bioceramic scaffolds (Mn/HSAE@BCP scaffolds). The integrated Mn/HSAE@BCP scaffolds can catalyze the conversion of H2O2 to produce hydroxyl radical (•OH) and superoxide anion (O2 •-) through cascade reaction. Besides, the prominent thermal conversion efficiency of Mn/HSAE@BCP scaffolds can be utilized for sonodynamic therapy (SDT). The synergetic strategy of chemodynamic therapy (CDT)/SDT enables the sufficient generation of reactive oxygen species (ROS) to kill Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli). Furthermore, the enhanced antibacterial efficacy of Mn/HSAE@BCP scaffolds is beneficial to upregulate the expression of osteogenesis-related markers (such as collagen 1(COL1), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteoprotegerin (OPG)) in vitro and further promote bone regeneration in vivo. The results demonstrate the good potential of Mn/HSAE@BCP scaffolds for the enhanced antibacterial activity and bone regeneration, which provide an effective method for the treatment of clinical infective bone defect.

Creation of Wood-Based Hierarchical Superstructures via In Situ Growth of ZIF-8 for Enhancing Mechanical Strength and Electromagnetic Shielding Performance.

Given the escalating prevalence of electromagnetic pollution, there is an urgent need for the development of high-performance electromagnetic interference (EMI) shielding materials. Herein, wood-based electromagnetic shielding materials have gained significant popularity due to their exceptional performance as building materials. In this study, a novel wood-based composite with electromagnetic shielding properties is developed. Through the in situ growth of zeolitic imidazolate framework-8 (ZIF-8) crystals on wood fibers, coupled with uniform integration of carbon nanotubes (CNTs), a multifunctional composite named ZIF-8/Poplar-CNT composite is synthesized via a one-step thermoforming process. The incorporation of CNTs endows the composites with excellent EMI shielding effectiveness (EMI SE). Among these elements, despite ZIF-8 crystals not possessing intrinsic electromagnetic shielding functionality, their distinctive dodecahedral structure proves adept at scattering and reflecting electromagnetic waves within the composites, further improving the electromagnetic shielding effect. Hence, the ZIF-8/Poplar-CNT composite (56.95 dB) has ≈10 dB higher EMI SE compared to that of the composites without ZIF-8 crystals. Meanwhile, ZIF-8 crystals endow the materials with excellent tensile strength (54.84 MPa, enhanced by 4 times). Moreover, the introduction of Zn2+ provides superior antibacterial properties. The potential applications of ZIF-8/Poplar-CNT composites extend to diverse areas such as building decoration, electronic products, and medical equipment.

Systemic delivery of proteins using novel peptides via the sublingual route.

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice.

3D hierarchic interfacial assembly of Au nanocage@Au along with IS-AgMNPs for simultaneous, ultrasensitive, reliable, and quantitative SERS detection of colorectal cancer related miRNAs.

Simultaneous, reliable, and ultra-sensitive analysis of promising miRNA biomarkers of colorectal cancer (CRC) in serum is critical for early diagnosis and prognosis of CRC. In this work, we proposed a novel 3D hierarchic assembly clusters-based SERS strategy with dual enrichment and enhancement designed for the ultrasensitive and quantitative analysis of two upregulated CRC-related miRNAs (miR-21 and miR-31). The biosensor contains the following: (1) SERS probe, Au nanocage@Au nanoparticles (AuNC@Au NPs) labeled with Raman reporters (RaRs). (2) magnetic capture unit, Ag-coated Fe3O4 magnetic nanoparticles (AgMNPs) modified with internal standard (IS). (3) signal amplify probes (SA probes) for the formation of hierarchic assembly clusters. Based on this sensing strategy, the intensity ratio IRaRs/IIS with Lg miRNAs presents a wide linear range (10 aM-100 pM) with a limit of detection of 3.46 aM for miR-21, 6.49 aM for miR-31, respectively. Moreover, the biosensor shows good specificity and anti-interference ability, and the reliability and repeatability of the strategy were then verified by practical detection of clinical serum. Finally, the biosensor can distinguish CRC cancer subjects from normal ones and guide the distinct tumor, lymph node, and metastasis (TNM) stages. Overall, benefiting from the face-to-face coupling of hierarchic assembly clusters, rapid magnetic enrichment and IS signal calibration of AgMNPs, the established biosensor achieves ultra-sensitive and simultaneous detection of dual miRNAs and opens potential avenues for prediction and staging of CRC.

Identification of a novel thermostable transaminase and its application in L-phosphinothricin biosynthesis.

Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase (PtTA) from Pseudomonas thermotolerans was mined and characterized. The PtTA showed a high specific activity (28.63 U/mg) towards 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. Two cascade systems driven by PtTA were developed for L-PPT biosynthesis, including asymmetric synthesis of L-PPT from PPO and deracemization of D, L-PPT. For the asymmetric synthesis of L-PPT from PPO, a three-enzyme cascade was constructed as a recombinant Escherichia coli (E. coli G), by co-expressing PtTA, glutamate dehydrogenase (GluDH) and D-glucose dehydrogenase (GDH). Complete conversion of 400 mM PPO was achieved using only 40 mM amino donor L-glutamate. Furthermore, by coupling D-amino acid aminotransferase (Ym DAAT) from Bacillus sp. YM-1 and PtTA, a two-transaminase cascade was developed for the one-pot deracemization of D, L-PPT. Under the highest reported substrate concentration (800 mM D, L-PPT), a 90.43% L-PPT yield was realized. The superior catalytic performance of the PtTA-driven cascade demonstrated that the thermodynamic limitation was overcome, highlighting its application prospect for L-PPT biosynthesis. KEY POINTS: • A novel thermostable transaminase was mined for L-phosphinothricin biosynthesis. • The asymmetric synthesis of L-phosphinothricin was achieved via a three-enzyme cascade. • Development of a two-transaminase cascade for D, L-phosphinothricin deracemization.

The elite eating quality alleles Wxb and ALKb are regulated by OsDOF18 and coordinately improve head rice yield.

Head rice yield (HRY) measures rice milling quality and determines final grain yield and commercial value. Here, we report that two major quantitative trait loci for milling quality in rice, qMq-1 and qMq-2, represent allelic variants of Waxylv/Waxyb (hereafter Wx) encoding Granule-Bound Starch Synthase I (GBSSI) and Alkali Spreading Value ALKc/ALKb encoding Soluble Starch Synthase IIa (SSIIa), respectively. Complementation and overexpression transgenic lines in indica and japonica backgrounds confirmed that Wx and ALK coordinately regulate HRY by affecting amylose content, the number of amylopectin branches, amyloplast size, and thus grain filling and hardness. The transcription factor OsDOF18 acts upstream of Wx and ALK by activating their transcription. Furthermore, rice accessions with Wxb and ALKb alleles showed improved HRY over those with Wxlv and ALKc. Our study not only reveals the novel molecular mechanism underlying the formation of HRY but also provides a strategy for breeding rice cultivars with improved HRY.

Prototype-Augmented Self-Supervised Generative Network for Generalized Zero-Shot Learning.

Generalized Zero-Shot Learning (GZSL) aims at recognizing images from both seen and unseen classes by constructing correspondences between visual images and semantic embedding. However, existing methods suffer from a strong bias problem, where unseen images in the target domain tend to be recognized as seen classes in the source domain. To address this issue, we propose a Prototype-augmented Self-supervised Generative Network by integrating self-supervised learning and prototype learning into a feature generating model for GZSL. The proposed model enjoys several advantages. First, we propose a Self-supervised Learning Module to exploit inter-domain relationships, where we introduce anchors as a bridge between seen and unseen categories. In the shared space, we pull the distribution of the target domain away from the source domain and obtain domain-aware features. To our best knowledge, this is the first work to introduce self-supervised learning into GZSL as learning guidance. Second, a Prototype Enhancing Module is proposed to utilize class prototypes to model reliable target domain distribution in finer granularity. In this module, a Prototype Alignment mechanism and a Prototype Dispersion mechanism are combined to guide the generation of better target class features with intra-class compactness and inter-class separability. Extensive experimental results on five standard benchmarks demonstrate that our model performs favorably against state-of-the-art GZSL methods.

Cell-penetrating peptides for transmucosal delivery of proteins.

Enabling non-invasive delivery of proteins across the mucosal barriers promises improved patient compliance and therapeutic efficacies. Cell-penetrating peptides (CPPs) are emerging as a promising and versatile tool to enhance protein and peptide permeation across various mucosal barriers. This review examines the structural and physicochemical attributes of the nasal, buccal, sublingual, and oral mucosa that hamper macromolecular delivery. Recent development of CPPs for overcoming those mucosal barriers for protein delivery is summarized and analyzed. Perspectives regarding current challenges and future research directions towards improving non-invasive transmucosal delivery of macromolecules for ultimate clinical translation are discussed.

Integrated Bioinformatics Analysis Reveals Diagnostic Biomarkers and Immune Cell Infiltration Characteristics of Solar Lentigines.

Background: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers. Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features. Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model's classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs. Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells. Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.