Left lower lobe sleeve resection for the clear cell variant of pulmonary mucoepidermoid carcinoma: A case report.

BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree. The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges, primarily attributable to its morphological similarity to other tumors containing clear cells. CASE SUMMARY: A 22-year-old male, formerly in good health, came in with a two-month duration of persistent cough and production of sputum. Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus, which resulted in complete atelectasis of the left lung. Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor, characterized by clear cell morphology in most of the tumor cells. The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection. Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion, leading to a definitive pathological diagnosis of the clear cell variant of PMEC, staged as T2N0M0. After surgery, the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period. CONCLUSION: This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male. The patient underwent successful left lower lobe sleeve resection. This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy, underscoring the importance of precise diagnosis and personalized treatment strategies.

Harzianic acids and oxazolidinone from the endophytic fungus Ilyonectria sp. and their cytotoxicity activity.

Four undescribed compounds including three harzianic acids (1, 3 and 4) and one oxazolidinone (2), along with three known ones (5-7) were isolated from the solid fermented product of endophytic fungus Ilyonectria sp., their structures were elucidated as 1-amino-harzianic acid (1), ilyonectria-oxazolidinone (2),10'-nor- isoharzianic acid (3), isohomoharzianic acid (4), harzianic acid (5), isoharzianic acid (6), homoharzianic acid (7) by means of detailed chemical evidences and spectroscopic data analysis. All the compounds were evaluated for cytotoxicity against SMMC-7721 human cancer cell lines by MTS assay. Among the seven tested compounds, 1-amino-harzianic acid (1) demonstrated well cytotoxic activity against SMMC-7721 with IC50 value of 26.84 µM. The results of molecular docking indicated that compound exhibited moderate anti-tumor activity may through binding to apoptosis related proteins.

High-risk event prone driver identification considering driving behavior temporal covariate shift.

Drivers who perform frequent high-risk events (e.g., hard braking maneuvers) pose a significant threat to traffic safety. Existing studies commonly estimated high-risk event occurrence probabilities based upon the assumption that data collected from different time periods are independent and identically distributed (referred to as i.i.d. assumption). Such approach ignored the issue of driving behavior temporal covariate shift, where the distributions of driving behavior factors vary over time. To fill the gap, this study targets at obtaining time-invariant driving behavior features and establishing their relationships with high-risk event occurrence probability. Specifically, a generalized modeling framework consisting of distribution characterization (DC) and distribution matching (DM) modules was proposed. The DC module split the whole dataset into several segments with the largest distribution gaps, while the DM module identified time-invariant driving behavior features through learning common knowledge among different segments. Then, gated recurrent unit (GRU) was employed to conduct time-invariant driving behavior feature mining for high-risk event occurrence probability estimation. Moreover, modified loss functions were introduced for imbalanced data learning caused by the rarity of high-risk events. The empirical analyses were conducted utilizing online ride-hailing services data. Experiment results showed that the proposed generalized modeling framework provided a 7.2% higher average precision compared to the traditional i.i.d. assumption based approach. The modified loss functions further improved the model performance by 3.8%. Finally, benefits for the driver management program improvement have been explored by a case study, demonstrating a 33.34% enhancement in the identification precision of high-risk event prone drivers.

Rapid and Precise Differentiation and Authentication of Agricultural Products via Deep Learning-Assisted Multiplex SERS Fingerprinting.

Accurate and rapid differentiation and authentication of agricultural products based on their origin and quality are crucial to ensuring food safety and quality control. However, similar chemical compositions and complex matrices often hinder precise identification, particularly for adulterated samples. Herein, we propose a novel method combining multiplex surface-enhanced Raman scattering (SERS) fingerprinting with a one-dimensional convolutional neural network (1D-CNN), which enables the effective differentiation of the category, origin, and grade of agricultural products. This strategy leverages three different SERS-active nanoparticles as multiplex sensors, each tailored to selectively amplify the signals of preferentially adsorbed chemicals within the sample. By strategically combining SERS spectra from different NPs, a 'SERS super-fingerprint' is constructed, offering a more comprehensive representation of the characteristic information on agricultural products. Subsequently, utilizing a custom-designed 1D-CNN model for feature extraction from the 'super-fingerprint' significantly enhances the predictive accuracy for agricultural products. This strategy successfully identified various agricultural products and simulated adulterated samples with exceptional accuracy, reaching 97.7% and 94.8%, respectively. Notably, the entire identification process, encompassing sample preparation, SERS measurement, and deep learning analysis, takes only 35 min. This development of deep learning-assisted multiplex SERS fingerprinting establishes a rapid and reliable method for the identification and authentication of agricultural products.

Comprehensive molecular characterisation of the complete mitogenome of Ergasilus tumidus and phylogenetic relationships of Copepoda inferred from mitogenomes.

Although parasitic copepods of the genus Ergasilus von Nordmann, 1832 are globally distributed parasites of fish, their phylogenetic relationships with other Copepoda are not clear, and the characteristics of their mitochondrial genomes (mitogenomes) are not thoroughly understood. The objective of this study was to address these knowledge gaps by sequencing the complete mitogenome of Ergasilus tumidus Markevich, 1940. The complete mitogenome (GenBank Acc. No. OQ596537) was 14,431 bp long and it comprised 13 protein-coding genes (PCGs), 22 tRNAs, two tRNAs, and two control regions (CRs). Phylogenetic analyses, conducted using concatenated nucleotide and amino acid sequences of 13 protein-coding genes, produced two partially incongruent topologies. While the order Calanoida was consistently resolved as the sister lineage to the other three orders, topological instability was observed in the relationships of the orders Cyclopoida, Siphonostomatoida and Harpacticoida. Siphonostomatoida clustered with Cyclopoida in the nucleotide-based phylogeny, but with Harpacticoida in the amino acid-based phylogeny. The latter topology conforms to the widely accepted relationships, but we speculate that the former topology is more likely to be the correct one. Our study provides a complete mitogenome sequence of E. tumidus, which helps us better understand the molecular evolution of the genus Ergasilus. Additionally, we suggest a different perspective on the controversial phylogenetic relationships among Siphonostomatoida, Cyclopoida and Harpacticoida, diverging from previously accepted views.

Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization.

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".

Application of microneedling in photodynamic therapy: A systematic review.

BACKGROUND: The application of photodynamic therapy (PDT) is pivotal in the management of diverse dermatologic conditions. Microneedling (MN) is a minimally invasive tool that is capable of inducing transient pores on the skin to facilitate transdermal drug delivery. Several studies have reported augmentation of PDT combined with MN. This systematic review analyzes the current studies on the efficacy and safety of MN-assisted PDT for skin diseases. METHODS: The literature search using the PRISMA standard was completed through PubMed, Embase, Web of Science and CENTRAL from the establishment of the databases to November 2023. Two independent researchers finished the procedure. RESULTS: A total of 12 articles and 413 subjects met our study criteria. This systematic review suggests that MN-assisted PDT can decrease the incubation time required for the photosensitizer and reduce skin lesions of actinic keratosis (AK) . The common side effect is pain and no serious adverse events were reported. CONCLUSIONS: MN is an effective method to increase the transdermal delivery rate of photosensitizers. For different photosensitizers and disease, MN may show different clinical effects.

Design and experiment of high-field asymmetric waveform ion mobility spectrometry chip based on an integrated temperature control printed circuit board structure.

RATIONALE: During the detection of volatile organic compounds (VOC) using high-field asymmetric waveform ion mobility spectrometry (FAIMS), the ambient temperature significantly impacts the accuracy of planar FAIMS. To mitigate the influence of ambient temperature on detection accuracy and enhance resolution, a FAIMS system based on the inner impedance characteristics of a printed circuit board (PCB) was designed for temperature control. METHODS: This study, conducted under standard atmospheric pressure, aimed to assess the signal stability of a planar FAIMS instrument with and without temperature control, and the effect of temperature change on the detection ability of acetone, ethanol, and their mixture was studied using PCB self-heating. RESULTS: Experimental results demonstrated that the base noise in FAIMS with temperature control was 0.2 pA, whereas that in FAIMS without temperature control was 1.8 pA. Notably, with increasing temperature, the detection ability of FAIMS changes accordingly. The optimal relative detection ability of acetone was observed when the electrode plate was heated to 45°C under an electric field of 15 kV/cm. CONCLUSIONS: This study provides a novel approach to improve the resolving power of FAIMS systems and their signal-to-noise ratio. The utilization of a PCB-based temperature control proved effective in stabilizing FAIMS signal characteristics and optimizing detection capabilities, particularly for VOCs such as acetone. These findings have significant implications for improving the accuracy and resolving power of FAIMS systems in VOC detection applications.

Exploring timescale-specific functional brain networks and their associations with aging and cognitive performance in a healthy cohort without dementia.

INTRODUCTION: Functional brain networks (FBNs) coordinate brain functions and are studied in fMRI using blood-oxygen-level-dependent (BOLD) signal correlations. Previous research links FBN changes to aging and cognitive decline, but various physiological factors influnce BOLD signals. Few studies have investigated the intrinsic components of the BOLD signal in different timescales using signal decomposition. This study aimed to explore differences between intrinsic FBNs and traditional BOLD-FBN, examining their associations with age and cognitive performance in a healthy cohort without dementia. MATERIALS AND METHODS: A total of 396 healthy participants without dementia (men = 157; women = 239; age range = 20-85 years) were enrolled in this study. The BOLD signal was decomposed into several intrinsic signals with different timescales using ensemble empirical mode decomposition, and FBNs were constructed based on both the BOLD and intrinsic signals. Subsequently, network features-global efficiency and local efficiency values-were estimated to determine their relationship with age and cognitive performance. RESULTS: The findings revealed that the global efficiency of traditional BOLD-FBN correlated significantly with age, with specific intrinsic FBNs contributing to these correlations. Moreover, local efficiency analysis demonstrated that intrinsic FBNs were more meaningful than traditional BOLD-FBN in identifying brain regions related to age and cognitive performance. CONCLUSIONS: These results underscore the importance of exploring timescales of BOLD signals when constructing FBN and highlight the relevance of specific intrinsic FBNs to aging and cognitive performance. Consequently, this decomposition-based FBN-building approach may offer valuable insights for future fMRI studies.

Tumor Immunotherapy-Related Information on Internet-Based Videos Commonly Used by the Chinese Population: Content Quality Analysis.

BACKGROUND: Tumor immunotherapy is an innovative treatment today, but there are limited data on the quality of immunotherapy information on social networks. Dissemination of misinformation through the internet is a major social issue. OBJECTIVE: Our objective was to characterize the quality of information and presence of misinformation about tumor immunotherapy on internet-based videos commonly used by the Chinese population. METHODS: Using the keyword "tumor immunotherapy" in Chinese, we searched TikTok, Tencent, iQIYI, and BiliBili on March 5, 2022. We reviewed the 118 screened videos using the Patient Education Materials Assessment Tool-a validated instrument to collect consumer health information. DISCERN quality criteria and the JAMA (Journal of the American Medical Association) Benchmark Criteria were used for assessing the quality and reliability of the health information. The videos' content was also evaluated. RESULTS: The 118 videos about tumor immunotherapy were mostly uploaded by channels dedicated to lectures, health-related animations, and interviews; their median length was 5 minutes, and 79% of them were published in and after 2018. The median understandability and actionability of the videos were 71% and 71%, respectively. However, the quality of information was moderate to poor on the validated DISCERN and JAMA assessments. Only 12 videos contained misinformation (score of >1 out of 5). Videos with a doctor (lectures and interviews) not only were significantly less likely to contain misinformation but also had better quality and a greater forwarding number. Moreover, the results showed that more than half of the videos contain little or no content on the risk factors and management of tumor immunotherapy. Overall, over half of the videos had some or more information on the definition, symptoms, evaluation, and outcomes of tumor immunotherapy. CONCLUSIONS: Although the quality of immunotherapy information on internet-based videos commonly used by Chinese people is moderate, these videos have less misinformation and better content. Caution must be exercised when using these videos as a source of tumor immunotherapy-related information.

Histological evaluation of monopolar and bipolar radiofrequency microneedling treatment in a porcine model.

BACKGROUND AND OBJECTIVE: Fractional radiofrequency microneedling (FRM) is widely used as an option for skin rejuvenation, however there is a lack of histological evidence for the various energy delivery systems available. The objective was to assess thermal denaturation of tissue and the wound healing response in monopolar mode versus bipolar mode. Histological analysis was performed to demonstrate the efficacy of automatic impedance feedback system in monopolar mode. STUDY DESIGN AND METHODS: In this study, the acute thermal effects caused by monopolar FRM treatment to the dorsal skin of pigs were assessed histologically by hematoxylin & eosin (H&E) staining. Then, one session of either monopolar or bipolar FRM was used to treat one or the other side of the pig using varying power levels and pulse widths. The acute and chronic tissue reactions were assessed using H&E, immunofluorescence, and western blot analysis at 0, 14, 30, and 90 days after treatment. The efficacy of the impedance feedback system was also monitored histologically. RESULTS: High-energy FRM treatment produced tissue loss and necrosis. The power level and pulse duration significantly affected the coagulation amount. Histopathology at 0, 14, 30, and 90 days showed that the skin tissue reaction was more pronounced for bipolar compared to monopolar FRM. Immunofluorescence showed the expression of TGF-ß, Ki67, MMP3, and elastin increased dramatically with both modes, but were higher in the bipolar FRM treated side. The automatic impedance feedback system could effectively adjust the output energy. CONCLUSIONS: We found that bipolar FRM produced greater thermal effects, more collagen coagulation, and more pronounced molecular changes compared with monopolar mode in a porcine animal model.

3D-printed bioink loading with stem cells and cellular vesicles for periodontitis-derived bone defect repair.

The suitable microenvironment of bone regeneration is critically important for periodontitis-derived bone defect repair. Three major challenges in achieving a robust osteogenic reaction are the exist of oral inflammation, pathogenic bacteria invasion and unaffluent seed cells. Herein, a customizable and multifunctional 3D-printing module was designed with glycidyl methacrylate (GMA) modified epsilon-poly-L-lysine (EPLGMA) loading periodontal ligament stem cells (PDLSCs) and myeloid-derived suppressive cells membrane vesicles (MDSCs-MV) bioink (EPLGMA/PDLSCs/MDSCs-MVs, abbreviated as EPM) for periodontitis-derived bone defect repair. The EPM showed excellent mechanical properties and physicochemical characteristics, providing a suitable microenvironment for bone regeneration.In vitro, EPMs presented effectively kill the periodontopathic bacteria depend on the natural antibacterial properties of the EPL. Meanwhile, MDSCs-MV was confirmed to inhibit T cells through CD73/CD39/adenosine signal pathway, exerting an anti-inflammatory role. Additionally, seed cells of PDLSCs provide an adequate supply for osteoblasts. Moreover, MDSCs-MV could significantly enhance the mineralizing capacity of PDLSCs-derived osteoblast. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that the EPM scaffold similarly had an excellent anti-inflammatory and bone regeneration efficacyin vivo. This biomimetic and multifunctional 3D-printing bioink opens new avenues for periodontitis-derived bone defect repair and future clinical application.

Comparison of 755-nm picosecond alexandrite laser versus 1064-nm Q-switched Nd:YAG laser for melasma: A randomized, split-face controlled, 2-year follow-up study.

OBJECTIVES: Pulsed laser treatment of melasma has shown some promising results. To compare the effectiveness and safety of 755-nm picosecond alexandrite laser (PSAL) fitted with diffractive lens array (DLA) versus 1064-nm Q-switched neodynimum:yttrium aluminum garnet laser (QSNYL) for the treatment of melasma. METHODS: We conducted a randomized, split face controlled, 2-year follow-up study. Each face was divided into two parts, each side receiving three treatments with either PSAL or QSNYL at 1 month intervals. Modified Melasma Area Severity Index scores (mMASI), pain scores, patient satisfaction and adverse events were recorded. In vivo reflectance confocal microscopy (RCM) images were acquired. RESULTS: Twenty subjects were enrolled and three dropped out. At 6 months, mMASI scores were significantly lower than baseline for QSNYL sides (p = 0.022), with no statistically significant difference between PSAL sides before and after treatment, PSAL sides versus QSNYL sides, or patient satisfaction scores. QSNYL treatment was associated with less pain (p = 0.014). No serious adverse events were reported. In the PSAL sides RCM showed a large number of dendritic melanocytes infiltrated in the dermis at 2 weeks and 4 weeks after treatment. Ten patients (58.82%) reported recurrence or exacerbation at 2-year follow-up with no statistically significant difference between the two lasers. CONCLUSIONS: QSNYL demonstrated short term clinical efficacy for melasma, but did not provide any additional benefit compared to PSAL with DLA. QSNYL was associated with less pain. There was a high recurrence rate at 2-year follow-up. RCM allowed the detection of cellular changes in melasma lesions.

Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

Geography, phylogeny and host switch drive the coevolution of parasitic Gyrodactylus flatworms and their hosts.

BACKGROUND: Gyrodactylus is a lineage of monogenean flatworm ectoparasites exhibiting many features that make them a suitable model to study the host-parasite coevolutionary dynamics. Previous coevolutionary studies of this lineage mainly relied on low-power datasets (a small number of samples and a single molecular marker) and (now) outdated algorithms. METHODS: To investigate the coevolutionary relationship of gyrodactylids and their fish hosts in high resolution, we used complete mitogenomes (including two newly sequenced Gyrodactylus species), a large number of species in the single-gene dataset, and four different coevolutionary algorithms. RESULTS: The overall coevolutionary fit between the parasites and hosts was consistently significant. Multiple indicators confirmed that gyrodactylids are generally highly host-specific parasites, but several species could parasitize either multiple (more than 5) or phylogenetically distant fish hosts. The molecular dating results indicated that gyrodactylids tend to evolve towards high host specificity. Speciation by host switch was identified as a more important speciation mode than co-speciation. Assuming that the ancestral host belonged to Cypriniformes, we inferred four major host switch events to non-Cypriniformes hosts (mostly Salmoniformes), all of which occurred deep in the evolutionary history. Despite their relative rarity, these events had strong macroevolutionary consequences for gyrodactylid diversity. For example, in our dataset, 57.28% of all studied gyrodactylids parasitized only non-Cypriniformes hosts, which implies that the evolutionary history of more than half of all included lineages could be traced back to these major host switch events. The geographical co-occurrence of fishes and gyrodactylids determined the host use by these gyrodactylids, and geography accounted for most of the phylogenetic signal in host use. CONCLUSIONS: Our findings suggest that the coevolution of Gyrodactylus flatworms and their hosts is largely driven by geography, phylogeny, and host switches.

Study of height, sitting height, lower extremity length, and the prevalence of short stature among elementary school students in the Tianyuan District of Zhuzhou City.

In this study, the height, sitting height, lower extremity length, growth status, and body proportions of elementary school students aged 6 to 12 years in Tianyuan District of Zhuzhou City, China, were analyzed. A total of 41,156 children from 38 elementary schools in the Tianyuan District of Zhuzhou City were selected for height measurement, employing the cluster sampling method. After the cluster data were obtained, the height and sitting height information were extracted, and calculations were performed for lower extremity length, sitting height-to-lower extremity length ratio, and sitting height-to-height ratio. Statistical analysis was conducted using SPSS 23.0 software. The height and sitting height measurements of boys and girls aged 6 to 12 years in Tianyuan District surpassed the 2005 national standard set for 9 cities, while the lower extremities of children within the 7 to 9 age range fell below the national standard. In alignment with the national average, the fitted curve representing height for both boys and girls aged 6 to 12 years in Tianyuan District exhibited an intersection point around 10 to 10.5 years. No discernible distinction was observed in the incidence of short stature, as analyzed through the P3 standard, between the fitted curve for Tianyuan District and the national standard. Moreover, tall children exhibited a significantly lower sitting height-to-height ratio compared to their shorter counterparts. The fitted height curve in Tianyuan District, Zhuzhou City, proves effective in discerning shorter-statured children within the region. Nevertheless, further research is warranted to elucidate the factors contributing to the comparatively shorter lower extremities observed in children from Tianyuan District, Zhuzhou City, in contrast to the national average.

TAT-W61 peptide attenuates neuronal injury through blocking the binding of S100b to the V-domain of Rage during ischemic stroke.

Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.

The role of microcomedones in acne: Moving from a description to treatment target?

A major factor in the pathogenesis of acne is ductal hyperproliferation in the pilosebaceous glands. This takes the form of invisible microcomedones and leads to the subsequent formation of both inflammatory and non-inflammatory clinical lesions. Microcomedones are the initial stage in the cyclical development of acne, so called comedogenesis. Microcomedones can be detected using cyanoacrylate skin surface stripping, electron microscopy, reflection confocal microscopy and other techniques. It has been proposed that the density and the size of microcomedones are positively correlated with acne severity. Thus, the purpose of this review is to summarize the root causes of acne, and suggest that treatment of microcomedones could, at least in part, resolve acne lesions and prevent relapse.