The causal relationship between serum metabolites and acne vulgaris: a Mendelian randomization study.

In individuals with acne vulgaris, alterations occur in serum metabolite composition, yet the exact causal link between these metabolites and acne development remains elusive. Using genome-wide association datasets, we performed bidirectional Mendelian randomization (MR) to investigate the potential causal relationship between 309 serum metabolites and acne vulgaris. We performed sensitivity analysis to evaluate the presence of heterogeneity and pleiotropy. Forward MR analysis found 14 serum metabolites significantly associated with acne vulgaris, and reverse MR analysis found no significant association between acne vulgaris and these serum metabolites. Through validation using data from the FinnGen database of acne vulgaris studies, we found a conclusive and significant correlation between stearoylcarnitine and acne vulgaris. This provides new evidence in the search for new targets for the treatment of acne vulgaris.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

Antibiotic-Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m6A Epitranscriptome via Bile Acid Metabolism.

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction (HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis (CIA) mouse model. Methods: DBA/1J female mice were used to establish the collagen-induced arthritis (CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay (ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors mRNA and protein levels after HGWD intervention in RAW 264.7 cells. Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints, reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function. HGWD decreased the expression of mRNA for inflammatory factors and the protein expression levels of p-NF-кB and IL-17. Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

The Time-Dependent Interfacial Adhesion between Artificial Rock and Fresh Mortar Modified by Nanoclay.

The time-dependent interfacial adhesion between rock and fresh mortar is key for printing concrete linings in mountain tunnels. However, a scientific deficit exists in the time-dependent evolution of the interfacial adhesion, which can cause adhesion failure when printing tunnel lining. Nanoclay has the potential to increase the interfacial adhesion and eliminate the adhesion failure. Before the actual printing of tunnel linings, the time-dependent interfacial adhesion between artificial rock and fresh mortar modified by nanoclay should be understood. This paper studied the time-dependent interfacial adhesion based on fast tack tests, fast shear tests, and isothermal calorimetry tests. With the addition of nanoclay, the maximum tensile stress and the maximum shear stress increased. Compared with a reference series, the maximum interfacial tensile stress in a 0.3% nanoclay series increased by 106% (resting time 1 min) and increased by 209% (resting time 32 min). A two-stage evolution of the interfacial adhesion was found with the addition of nanoclay. In the first stage, the time-dependent interfacial adhesion increased rapidly. A 0.3% NC series showed an increase rate six times higher than that of the reference series. As the matrices aged, the increase rate slowed down and followed a linear pattern of increase, still higher than that of the reference series. The stiffening of fresh matrices resulted in the interface failure mode transition from a ductile failure to a brittle failure. The effect of nanoclay on flocculation and on accelerating the hydration contributed to the time-dependent interfacial adhesion between artificial rock and fresh mortar.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain.

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Fine-grained image classification on bats using VGG16-CBAM: a practical example with 7 horseshoe bats taxa (CHIROPTERA: Rhinolophidae: Rhinolophus) from Southern China.

BACKGROUND: Rapid identification and classification of bats are critical for practical applications. However, species identification of bats is a typically detrimental and time-consuming manual task that depends on taxonomists and well-trained experts. Deep Convolutional Neural Networks (DCNNs) provide a practical approach for the extraction of the visual features and classification of objects, with potential application for bat classification. RESULTS: In this study, we investigated the capability of deep learning models to classify 7 horseshoe bat taxa (CHIROPTERA: Rhinolophus) from Southern China. We constructed an image dataset of 879 front, oblique, and lateral targeted facial images of live individuals collected during surveys between 2012 and 2021. All images were taken using a standard photograph protocol and setting aimed at enhancing the effectiveness of the DCNNs classification. The results demonstrated that our customized VGG16-CBAM model achieved up to 92.15% classification accuracy with better performance than other mainstream models. Furthermore, the Grad-CAM visualization reveals that the model pays more attention to the taxonomic key regions in the decision-making process, and these regions are often preferred by bat taxonomists for the classification of horseshoe bats, corroborating the validity of our methods. CONCLUSION: Our finding will inspire further research on image-based automatic classification of chiropteran species for early detection and potential application in taxonomy.

Endoscopic submucosal dissection for the treatment of a large inflammatory fibroid polyp in the gastric antrum prolapsing into the duodenum: A case report.

RATIONALE: Inflammatory fibroid polyp (IFP), also known as Vanek tumor, is a rare, benign gastrointestinal lesion characterized by its inflammatory and fibroid histological features. IFP is often discovered incidentally during endoscopic examinations. It is exceedingly rare for an IFP to prolapse into the duodenum and results in incomplete obstruction of the pylorus. PATIENT CONCERNS: A 64-year-old male patient was admitted to the hospital with recurrent episodes of melena over a 6-month period, along with complaints of dizziness and fatigue in the past 10 days. DIAGNOSES: Gastroscopy showed a giant polypoid mass on the posterior wall of the gastric antrum, prolapsing into the duodenum. Abdominal computer tomography (CT) confirmed the tumor protruding into the duodenum. Pathologic examination of the resected specimen confirmed the IFP diagnosis. INTERVENTIONS: The giant tumor was completely and successfully excised using endoscopic submucosal dissection (ESD). After the surgery, the patient underwent acid suppression and fluid replenishment therapy. OUTCOMES: The patient responded well to ESD and was discharged in stable condition. As of the submission of the case report, there has been no recurrence of the tumor after a 5-month follow-up, and the patient is still under follow-up. LESSONS: While IFPs have traditionally been managed surgically, ESD demonstrates promising treatment outcomes, avoiding the need for surgical distal gastrectomy, and emerges as a safe and effective treatment option.

Multistatic Integrated Sensing and Communication System Based on Macro-Micro Cooperation.

A novel multistatic integrated sensing and communication (ISAC) system based on macro-micro cooperation for the sixth-generation (6G) mobile network is proposed. Instead of using macrosites at both the transmitter and receiver sides, microsites are considered as receivers in cooperative sensing. This system is important since microsites can be deployed more flexibly to reduce their distances to the sensing objects, providing better coverage for sensing service. In this work, we first analyze the deployment problem of microsites, which can be deployed along the radius and azimuth angle to cover macrosite cells. The coverage area of each microsite is derived in terms of its position in the cell. Then, we describe an efficient estimating approach for obtaining the position and velocity of sensing objects in the macrosite cell. By choosing multiple microsites around the targeted sensing area, joint data processing with an efficient optimization method is also provided. Simulation results show that the multistatic ISAC system employing macro-micro cooperation can improve the position and velocity estimation accuracy of objects compared to systems employing macrosite cooperation alone, demonstrating the effectiveness and potential for implementing the proposed system in the 6G mobile network.

Observation on the tilt and decentration of multifocal intraocular lens with optic capture in Berger space for pediatric cataract.

PURPOSE: This study aimed to observe the tilt and decentration of multifocal intraocular lens (IOL) with optic capture in Berger space within 2 years after pediatric cataract surgery. METHODS: This is a prospective observational study. The implantation of multifocal IOL (Tecnis ZMB00) with optic capture in Berger space was performed on 33 patients (48 eyes) with pediatric cataract at Qingdao Eye Hospital. Tilt and decentration of IOL was measured using Scheimpflug system (Pentacam) at 1 month and 2 years postoperatively. RESULTS: All the multifocal IOLs were successfully implanted in Berger space with optic capture and no visually significant complications were detected during the follow-up. The mean tilt of IOLs was 2.779° ± 0.950° in the vertical plane and 2.399° ± 0.898° in the horizontal plane at 1 month postoperatively, and the mean length of the decentration was 0.207 ± 0.081 mm in vertical plane and 0.211 ± 0.090 mm in the horizontal plane. Compared with 1 month after surgery, the angle of tilt decreased by a mean of 0.192° and decentration increased by a mean of 0.014 mm at the vertical meridian at 2 years postoperatively (P = 0.37 and P = 0.27, respectively), meanwhile, tilt increased by 0.265° and decentration increased by 0.012 mm at the horizontal meridian (P = 0.11 and P = 0.22, respectively). CONCLUSIONS: The follow-up results suggest the tilt and decentration of multifocal IOL implantation with optic capture in Berger space remain stable in an acceptable range within 2 years after cataract surgery in children above the age of 5. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Qingdao Eye Hospital, and registered on Chinese Clinical Trial Registry (ChiCTR identifier: 1900023155).

Simultaneous Determination of One-Carbon Folate Metabolites and One-Carbon-Related Amino Acids in Biological Samples Using a UHPLC-MS/MS Method.

One-carbon folate metabolites and one-carbon-related amino acids play an important role in human physiology, and their detection in biological samples is essential. However, poor stability as well as low concentrations and occurrence in different species in various biological samples make their quantification very challenging. The aim of this study was to develop a simple, fast, and sensitive ultra-high-performance liquid chromatography MS/MS (UHPLC-MS/MS) method for the simultaneous quantification of various one-carbon folate metabolites (folic acid (FA), tetrahydrofolic acid (THF), p-aminobenzoyl-L-glutamic acid (pABG), 5-formyltetrahydrofolic acid (5-CHOTHF), 5-methyltetrahydrofolic acid (5-CH3THF), 10-formylfolic acid (10-CHOFA), 5,10-methenyl-5,6,7,8-tetrahydrofolic acid (5,10-CH+-THF), and 4-α-hydroxy-5-methyltetrahydrofolate (hmTHF)) and one-carbon-related amino acids (homocysteine (Hcy), methionine (Met), S-ade-L-homocysteine (SAH), and S-ade-L-methionine (SAM)). The method was standardized and validated by determining the selectivity, carryover, limits of detection, limits of quantitation, linearity, precision, accuracy, recovery, and matrix effects. The extraction methods were optimized with respect to several factors: protease-amylase treatment on embryos, deconjugation time, methanol precipitation, and proteins' isoelectric point precipitation on the folate recovery. Ten one-carbon folate metabolites and four one-carbon-related amino acids were detected using the UHPLC-MS/MS technique in various biological samples. The measured values of folate in human plasma, serum, and whole blood (WB) lay within the concentration range for normal donors. The contents of each analyte in mouse plasma were as follows: pABG (864.0 nmol/L), 5-CH3THF (202.2 nmol/L), hmTHF (122.2 nmol/L), Met (8.63 µmol/L), and SAH (0.06 µmol/L). The concentration of each analyte in mouse embryos were as follows: SAM (1.09 µg/g), SAH (0.13 µg/g), Met (16.5 µg/g), 5,10-CH+THF (74.3 ng/g), pABG (20.6 ng/g), and 5-CH3THF (185.4 ng/g). A simple and rapid sample preparation and UHPLC-MS/MS method was developed and validated for the simultaneous determination of the one-carbon-related folate metabolites and one-carbon-related amino acids in different biological samples.

Analysis aqueous humor lipid profile of neovascular glaucoma secondary to diabetic retinopathy and lipidomic alteration response to anti-VEGF treatment.

The objective of this study was to examine the lipid spectrum of aqueous humor (AH) in patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy and to investigate the lipid alteration response to anti-vascular endothelial growth factor (anti-VEGF) treatment. Lipidomic analysis using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted to compare the lipid profiles of the AH in NVG patients with those of a control group. Lipid changes in the AH of NVG patients before and after intravitreal conbercept injections were also evaluated. The identification of lipids showing differential expression was accomplished through both multivariate and univariate analyses. This study included 13 NVG patients and 20 control subjects. Based on LipidSearch software, 639 lipid species across 33 lipid classes were detected in the participants' AH. The combination of univariate and multivariate statistical analyses yielded 53 differentially expressed lipids (VIP >1 and P < 0.05). In addition, 9 lipids were found to be differentially expressed before and after the intravitreal conbercept injections in the NVG patients. Significant alterations in the metabolic pathways of glycerophospholipid and glycerolipid exhibited notable changes. Our results highlighted the lipid changes in patients' AH in relation to the progression of NVG, and indicated that the modified lipids could potentially be utilized as therapeutic targets for NVG.

Pan-cancer analysis reveals a regulatory pattern of anoikis in human cancers.

Anoikis emerges when a cell finds itself extricated from the appropriate extracellular matrix, leading to an interruption in integrin ligation and thus triggering programmed cellular demise. The cardinal role of Anoikis in the realms of tumor invasion and metastasis is undeniable, although our grasp on its precise influence within the convoluted landscape of cancer biology remains somewhat circumscribed. Notably, both the immune milieu of the tumor and its inherent aggression are correlated with the fluctuating variables of Anoikis. We conducted a thorough evaluation of the genes associated with anoikis and studied the regulatory patterns of these genes as well as the prognostic impact of anoikis in 33 different types of tumors. We provided functional annotations for the regulatory patterns linked to Anoikis. Additionally, we described the associations between immunological factors and genes associated with Anoikis. By applying gene set variation analysis (GSVA), we utilized the inherent abilities of 34 basic genes to calculate the Anoikis index. The Anoikis index is closely related to prognosis, immune microenvironment, immunotherapy, and other aspects. Our functional research revealed a correlation between immune cell infiltration, EMT, and a regulatory gene that is synonymous with adverse survival outcomes. In addition, our observations revealed a direct relationship between the expression of CEACAM5 and CEACAM6,the amplification of epithelial mesenchymal transition (EMT) phenomenon, and a decrease in survival outcomes.The potential therapeutic utility of anoikis-related genes was highlighted by the possible links between TME, clinical samples, genetic mutations, drug resistance, and immunotherapy.

Characterization of bacterial diversity and screening of cellulose-degrading bacteria in the gut system of Glenea cantor (Fabricius) larvae.

The intestinal bacteria of longhorn beetles would be ideal targets for pest control and lignocellulosic resources by destroying or exploiting their cellulose-degrading function. This article aims to investigate the diversity and community structure of intestinal bacteria the oligophagous longhorn beetle Glenea cantor. Additionally, it seeks to identify the presence of lignocellulose-degrading bacteria in the gut, and explore their role in consuming host kapok trees Bombax malabaricum. In this study, the bacterial community from G. cantor was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) targeting the V3 and V4 regions. A total of 563,201 valid sequences and 814 OTUs were obtained. The dominant phyla were Proteobacteria, and the dominant genera were Acinetobacter and Lactococcus. The analysis of microbial diversity revealed a high bacterial diversity in the samples, with the gut bacteria playing a crucial role in the physiological activities of the host, particularly, 9 genera of intestinal bacteria with cellulose degradation function were found, highlighting their vital role in cellulose degradation. Five strains of cellulose-degrading bacteria, belonging to the genus Pseudomonas, were obtained from the intestinal tract of G. cantor larvae using traditional isolation and culture techniques as well as 16S rDNA sequencing. Among these strains, A4 exhibited a cellulase activity of 94.42 ± 0.42 U/mL, while A5 displayed the highest filter paper enzyme activity of 127.46 ± 3.54 U/mL. These results offered valuable insights into potential targets for pest control through internal attack digestion and cellulose-degrading bacteria in longhorn beetles.

Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway.

Lactate dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Coactosin-Like Protein 1 (COTL1) Could Be an Immunological and Prognostic Biomarker: From Pan-Cancer Analysis to Low-Grade Glioma Validation.

Background: Cancer represents a widespread global health challenge impacting millions of individuals worldwide. Identifying new targets for cancer treatment is a crucial step in developing more effective therapies. Among these potential targets, Coactosin-like protein 1 (COTL1), a cytoskeleton-associated protein with critical roles in cell migration, adhesion, and signaling, has shown involvement in tumor progression. Methods: GSCA, TIMER, SangerBox database were used to explore the COTL1 expression across different tumor types. We employed the TCGA Pan-Atlas Cancer Genomics Dataset, which is available through the cBioportal platform, to explore genetic alterations in COTL1. We conduct a comprehensive analysis of COTL1, encompassing gene expression, clinical prognosis, RNA modification, immunotherapy, and cancer stemness through SangerBox database. Clinical samples were validated using immunohistochemistry. Results: Our analysis revealed that COTL1 is highly expressed in most cancers and correlates with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts. Furthermore, COTL1 was found to be associated with DNA and RNA stemness in 20 and 22 different tumor types, respectively. Additionally, COTL1 showed positive correlations with immunological checkpoints and immune infiltration cells. It was also linked to tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1), all of which are potential targets for immunotherapies. Moreover, a favorable relationship was demonstrated between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant allele tumor heterogeneity (MATH) with COTL1. Furthermore, our findings confirmed a positive correlation between COTL1 expression, CD8, and PD-L1 in LGG, as well as an association of high COTL1 expression with decreased patient survival in LGG. Conclusion: Based on these compelling findings, COTL1 may hold significant clinical implications for the development of novel cancer therapies and serve as a potential target for tumors associated with immunotherapy in the future.

NEAT1 Deficiency Promotes Corneal Epithelial Wound Healing by Activating cAMP Signaling Pathway.

Purpose: This study aimed to investigate the role of the long non-coding RNA (lncRNA) NEAT1 in corneal epithelial wound healing in mice. Methods: The central corneal epithelium of wild-type (WT), MALAT1 knockout (M-KO), NEAT1 knockout (N-KO), and NEAT1 knockdown (N-KD) mice was scraped to evaluate corneal epithelial and nerve regeneration rates. RNA sequencing of the corneal epithelium from WT and N-KO mice was performed 24 hours after debridement to determine the role of NEAT1. Quantitative PCR (qPCR) and ELISA were used to confirm the bioinformatic analysis. The effects of the cAMP signaling pathway were evaluated in N-KO and N-KD mice using SQ22536, an adenylate cyclase inhibitor. Results: Central corneal epithelial debridement in N-KO mice significantly promoted epithelial and nerve regeneration rates while suppressing inflammatory cell infiltration. Furthermore, the expression of Atp1a2, Ppp1r1b, Calm4, and Cngb1, which are key components of the cAMP signaling pathway, was upregulated in N-KO mice, indicative of its activation. Furthermore, the cAMP pathway inhibitor SQ22536 reversed the accelerated corneal epithelial wound healing in both N-KO and N-KD mice. Conclusions: NEAT1 deficiency contributes to epithelial repair during corneal wound healing by activating the cAMP signaling pathway, thereby highlighting a potential therapeutic strategy for corneal epithelial diseases.

Recent advances in extracellular vesicles for therapeutic cargo delivery.

Exosomes, which are nanosized vesicles secreted by cells, are attracting increasing interest in the field of biomedical research due to their unique properties, including biocompatibility, cargo loading capacity, and deep tissue penetration. They serve as natural signaling agents in intercellular communication, and their inherent ability to carry proteins, lipids, and nucleic acids endows them with remarkable therapeutic potential. Thus, exosomes can be exploited for diverse therapeutic applications, including chemotherapy, gene therapy, and photothermal therapy. Moreover, their capacity for homotypic targeting and self-recognition provides opportunities for personalized medicine. Despite their advantages as novel therapeutic agents, there are several challenges in optimizing cargo loading efficiency and structural stability and in defining exosome origins. Future research should include the development of large-scale, quality-controllable production methods, the refinement of drug loading strategies, and extensive in vivo studies and clinical trials. Despite the unresolved difficulties, the use of exosomes as efficient, stable, and safe therapeutic delivery systems is an interesting area in biomedical research. Therefore, this review describes exosomes and summarizes cutting-edge studies published in high-impact journals that have introduced novel or enhanced therapeutic effects using exosomes as a drug delivery system in the past 2 years. We provide an informative overview of the current state of exosome research, highlighting the unique properties and therapeutic applications of exosomes. We also emphasize challenges and future directions, underscoring the importance of addressing key issues in the field. With this review, we encourage researchers to further develop exosome-based drugs for clinical application, as such drugs may be among the most promising next-generation therapeutics.