Synthesis of Rhenium-Doped Copper Twin Boundary for High-Turnover-Frequency Electrochemical Nitrogen Reduction.

The precise design and synthesis of active sites to improve catalyst's performance has emerged as a promising tactic for electrochemistry. However, it is challenging to combine different types of active sites and manipulate them simultaneously at atomic resolution. Here, we present a strategy to synthesize Re atom-doped Cu twin boundaries (TBs), through pulsed electrodeposition and boundary segregation. The Re-doped Cu TBs demonstrate a highly efficient nitrogen reduction reaction (NRR) performance. Re-doped Cu TBs showed a turnover frequency of ∼5889 s-1, ∼800 times higher than the pure Cu TB active centers (∼7 s-1). In addition to the "acceptance-donation" activation of N2 molecules, theoretical calculations also reveal that the Re-Re dimer on TB can boost the NRR and impede the hydrogen evolution reaction synchronously, rendering Re-doped Cu TB catalysts with high NRR activity and selectivity.

Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study.

BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .

Substrate and functional characterization of the lysine acetyltransferase MsKat and deacetylase MsCobB in Mycobacterium smegmatis.

Tuberculosis (TB) is a serious cause of infectious death worldwide. Recent studies have reported that about 30% of the Mtb proteome was modified post-translationally, indicating that their functions are essential for drug resistance, mycobacterial survival, and pathogenicity. Among them, lysine acetylation, reversibly regulated by acetyltransferase and deacetylase, has important roles involved in energy metabolism, cellular adaptation, and protein interactions. However, the substrate and biological functions of these two important regulatory enzymes remain unclear. Herein, we utilized the non-pathogenic M. smegmatis strain as a model and systematically investigated the dynamic proteome changes in response to the overexpressing of MsKat/MsCobB in mycobacteria. A total of 4179 proteins and 1236 acetylated sites were identified in our data. Further analysis of the dynamic changes involved in proteome and acetylome showed that MsKat/MsCobB played a regulatory role in various metabolic pathways and nucleic acid processes. After that, the quantitative mass spectrometric method was utilized and proved that the AMP-dependent synthetase, Citrate synthase, ATP-dependent specificity component of the Clp protease, and ATP-dependent DNA/RNA helicases were identified to be the substrates of MsKat. Overall, our study provided an important resource underlying the substrates and functions of the acetylation regulatory enzymes in mycobacteria. SIGNIFICANCE: In this study, we systematically analyzed the dynamic molecular changes in response to the MsKat/MsCobB overexpression in mycobacteria at proteome and lysine acetylation level by using a TMT-based quantitative proteomic approach. Pathways related with glycolysis, degradation of branched chain amino acids, phosphotransferase system were affected after disturbance of the two regulates enzymes involved in lysine acetylation. We also proved that AMP-dependent synthetase Clp protease, ATP-dependent DNA/RNA helicases and citrate synthase was the substrate of MsKat according to our proteomic data and biological validation. Together, our study underlined the substrates and functions of the acetylation regulatory enzymes in mycobacteria.

Recent Advances in Material Technology for Leukemia Treatments.

Leukemia is a widespread hematological malignancy characterized by an elevated white blood cell count in both the blood and the bone marrow. Despite notable advancements in leukemia intervention in the clinic, a large proportion of patients, especially acute leukemia patients, fail to achieve long-term remission or complete remission following treatment. Therefore, leukemia therapy necessitates optimization to meet the treatment requirements. In recent years, a multitude of materials have undergone rigorous study to serve as delivery vectors or direct intervention agents to bolster the effectiveness of leukemia therapy. These materials include liposomes, protein-based materials, polymeric materials, cell-derived materials, and inorganic materials. They possess unique characteristics and are applied in a broad array of therapeutic modalities, including chemotherapy, gene therapy, immunotherapy, radiotherapy, hematopoietic stem cell transplantation, and other evolving treatments. Here, an overview of these materials is presented, describing their physicochemical properties, their role in leukemia treatment, and the challenges they face in the context of clinical translation. This review inspires researchers to further develop various materials that can be used to augment the efficacy of multiple therapeutic modalities for novel applications in leukemia treatment.

Strategies to Enhance l-Isoleucine Synthesis by Modifying the Threonine Metabolism Pathway in Escherichia coli.

l-threonine as an important precursor substance of l-isoleucine and improving its accumulation in Escherichia coli became an important idea to construct a chassis strain with high l-isoleucine production. Meanwhile, the effect of l-threonine metabolic pathway disruption in E. coli for the improved production of l-isoleucine remains unrevealed. In the present study, a mutant strain of E. coli was engineered by inactivating specific metabolic pathways (e.g., Δtdh, ΔltaE, and ΔyiaY) that were associated with l-threonine metabolism but unrelated to l-isoleucine synthesis. This was done with the aim to reduce the breakdown of l-threonine and, thereby, increase the production of l-isoleucine. The results obtained demonstrated a 72.3% increment in l-isoleucine production from 4.34 to 7.48 g·L-1 in the mutant strain compared with the original strain, with an unexpected 10.3% increment in bacterial growth as measured at OD600. Transcriptome analysis was also conducted on both the mutant strain NXU102 and the original strain NXU101 in the present study to gain a comprehensive understanding of their physiological attributes. The findings revealed a notable disparity in 1294 genes between the two strains, with 658 genes exhibiting up-regulation and 636 genes displaying down-regulation. The activity of tricarboxylic acid (TCA) cycle-related genes was found to decrease, but oxidative phosphorylation-related genes were highly up-regulated, which explained the increased activity of the mutant strain. For instance, l-lysine catabolism-related genes were found to be up-regulated, which reconfigured the carbon flow into the TCA cycle. The augmentation of acetic acid degradation pathway-related genes assisted in the reduction in acetic acid accumulation that could retard cell growth. Notably, substantial up-regulation of the majority of genes within the aspartate pathway could potentially account for the increased production of l-isoleucine in the present study. In this paper, a chassis strain with an l-isoleucine yield of 7.48 g·L-1 was successfully constructed by cutting off the threonine metabolic pathway. Meanwhile, transcriptomic analysis revealed that the cutting off of the threonine metabolic pathway induced perturbation of genes related to the pathways associated with the synthesis of l-isoleucine, such as the tricarboxylic acid cycle, glycolysis, and aspartic acid pathway.

Highly Efficient Hemostatic Cross-Linked Polyacrylate Polymer Dressings for Immediate Hemostasis.

A traumatic hemorrhage is fatal due to the great loss of blood in a short period of time; however, there are a few biomaterials that can stop the bleeding quickly due to the limited water absorption speed. Here, a highly absorbent polymer (HPA), polyacrylate, was prepared as it has the best structure-effectiveness relationship. Within a very short period of time (2 min), HPA continually absorbed water until it swelled up to its 600 times its weight; more importantly, the porous structure comprised the swollen dressing. This instantaneous swelling immediately led to rapid hemostasis in irregular wounds. We optimized the HPA preparation process to obtain a rapidly water-absorbent polymer (i.e., HPA-5). HPA-5 showed favorable adhesion and biocompatibility in vitro. A rat femoral arteriovenous complete shear model and a tail arteriovenous injury model were established. HPA exhibited excellent hemostatic capability with little blood loss and short hemostatic time compared with CeloxTM in both of the models. The hemostatic mechanisms of HPA consist of fast clotting by aggregating blood cells, activating platelets, and accelerating the coagulation pathway via water absorption and electrostatic interaction. HPA is a promising highly water-absorbent hemostatic dressing for rapid and extensive blood clotting after vessel injury.

SLPA-Net: a real-time recognition network for intelligent stomata localization and phenotypic analysis.

Plant stomatal phenotype traits play an important role in improving crop water use efficiency, stress resistance and yield. However, at present, the acquisition of phenotype traits mainly relies on manual measurement, which is time-consuming and laborious. In order to obtain high-throughput stomatal phenotype traits, we proposed a real-time recognition network SLPA-Net for stomata localization and phenotypic analysis. After locating and identifying stomatal density data, ellipse fitting is used to automatically obtain phenotype data such as apertures. Aiming at the problems of small stomata and high similarity to background, we introduced ECANet to improve the accuracy of stoma and aperture location. In order to effectively alleviate the unbalance problem in bounding box regression, we replaced the Loss function with a more effective Focal EIoU Loss. The experimental results show that SLPA-Net has excellent performance in the migration generalization and robustness of stomata and apertures detection and identification, as well as the correlation between stomata phenotype data obtained and artificial data. For convenience, we developed SLPA-Net into a freely available software, the software can be obtained at https://github.com/AITAhenu/SLPA.

Immune-Related Molecules CD3G and FERMT3: Novel Biomarkers Associated with Sepsis.

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein-protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1ß and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.

Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.

Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.

A novel method to quantify chitosan in aqueous solutions by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

In this study, a novel and accurate quantitative analysis method for the direct determination of chitosan (CS) in aqueous solutions using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is presented. By detecting the mass spectrum response intensity of a series of CS characteristic ion pairs, the sample concentration (abscissa) was linearly fitted with the total ion current (TIC) response intensity of its characteristic ion pairs (ordinate). A reliable standard curve was derived for quantifying CS in the range of 125-4000 ng/mL. Under the detection conditions, this CS quantification method yielded acceptable specificity (no interference peak), linearity (with correlation coefficient (r2) values >0.999), precision (acceptable limit RSDr < 3 %, RSDR < 6 %), accuracy (RE within the acceptable limits of ±5 %), and stability (acceptable limit RE within ±5 %, RSDr < 3 %). Moreover, the applicability of measurement was verified when a series of substrates did not interact with CS in the solution. Results have verified the applicability of this method for determining CS content in different composites. This study provides a method for determining CS content with significant practical value and economic benefit.

Metadherin inhibits chemosensitivity of triple-negative breast cancer to paclitaxel via activation of AKT/GSK-3ß signaling pathway.

Triple-negative breast cancer (TNBC) has an aggressive clinical course, and paclitaxel (PTX)-based chemotherapy remains the main therapeutic drug. Metadherin (MTDH) acts as an oncogene that regulates proliferation, invasion, metastasis, and chemoresistance. This study aimed to investigate whether TNBC chemosensitivity to PTX was related to the MTDH/AKT/glycogen synthase kinase-3beta (GSK-3ß) pathway. Clinical baseline characteristics and immunohistochemistry (IHC) were used to evaluate the expression and prognosis of MTDH and AKT (protein kinase B, PKB) in TNBC patient samples. MTDH shRNA, MTDH overexpression vector, MK-2206, and PTX intervention were used in cell models and mouse tumor-bearing models. Afterwards, mRNA and protein levels were assessed using quantitative real-time polymerase chain reaction and Western blot. Evaluate the level of tumor cell apoptosis and cell cycle using flow cytometry. Cell viability was detected using Cell Count Kit 8. The in vivo imaging system is used to analyze the growth of tumors. We found that higher expression of MTDH or AKT resulted in poorer disease-free survival and a lower Miller-Payne grade. MTDH promotes cell proliferation and increases p-AKT and p-GSK-3ß expression in TNBC cells. Notably, suppression of AKT terminated MTDH overexpression-induced cell proliferation and apoptosis. MTDH knockdown or the AKT inhibitor MK2206 reduced the p-AKT and p-GSK-3ß ratio, reduced cell viability and proliferation, increased cell apoptosis, and increased chemosensitivity to PTX. In vivo, xenograft tumors of an MTDH knockdown+MK2206 group treated with PTX were the smallest compared to other groups. In short, MTDH inhibits TNBC chemosensitivity to PTX by activating the AKT/GSK-3ß signaling pathway.

Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization.

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.

Hypertrophic cardiomyopathy secondary to deficiency in lysosome-associated membrane protein-2: A case report.

BACKGROUND: Danon disease (DD), in which mutations in the X-linked lysosome-associated membrane protein-2 (LAMP-2) gene result in hypertrophic cardiomyopathy, is a rare disease, reported primarily in small samples or cases. However, with the development of cardiac magnetic resonance imaging and genetic technology in recent years, the number of reports has increased. CASE SUMMARY: We report a case of DD in an adolescent male patient, confirmed by genetic testing. The patient was admitted to our hospital with complaints of a three-year history of chest tightness and shortness of breath. His preliminary clinical diagnosis is hypertrophic cardiomyopathy. Our report includes the patient's clinical course from hospital admission to death, step-by-step diagnosis, treatment course, and noninvasive imaging features. We highlight how a noninvasive diagnostic approach, based solely on clinical and imaging "red flags" for DD, can be used to achieve a diagnosis of DD with a high degree of confidence. CONCLUSION: DD is a very dangerous cardiomyopathy, and it is necessary to achieve early diagnosis and treatment.

Mask R-CNN provides efficient and accurate measurement of chondrocyte viability in the label-free assessment of articular cartilage.

Objective: Chondrocyte viability (CV) can be measured with the label-free method using second harmonic generation (SHG) and two-photon excitation autofluorescence (TPAF) imaging. To automate the image processing for the label-free CV measurement, we previously demonstrated a two-step deep-learning method: Step 1 used a U-Net to segment the lacuna area on SHG images; Step 2 used dual CNN networks to count live cells and the total number of cells in extracted cell clusters from TPAF images. This study aims to develop one-step deep learning methods to improve the efficiency of CV measurement. Method: TPAF/SHG images were acquired simultaneously on cartilage samples from rats and pigs using two-photon microscopes and were merged to form RGB color images with red, green, and blue channels assigned to emission bands of oxidized flavoproteins, reduced forms of nicotinamide adenine dinucleotide, and SHG signals, respectively. Based on the Mask R-CNN, we designed a deep learning network and its denoising version using Wiener deconvolution for CV measurement. Results: Using training and test datasets from rat and porcine cartilage, we have demonstrated that Mask R-CNN-based networks can segment and classify individual cells with a single-step processing flow. The absolute error (difference between the measured and the ground-truth CV) of the CV measurement using the Mask R-CNN with or without Wiener deconvolution denoising reaches 0.01 or 0.08, respectively; the error of the previous CV networks is 0.18, significantly larger than that of the Mask R-CNN methods. Conclusions: Mask R-CNN-based deep-learning networks improve efficiency and accuracy of the label-free CV measurement.

Management of autofluorescence in formaldehyde-fixed myocardium: choosing the right treatment.

Autofluorescence (AF) poses challenges for detecting proteins of interest in situ when employing immunofluorescence (IF) microscopy. This interference is particularly pronounced in strongly autofluorescent tissues such as myocardium, where tissue AF can be comparable to IF. Although various histochemical methods have been developed to achieve effective AF suppression in different types of tissue, their applications on myocardial  samples have not been well validated. Due to inconsistency across different autofluorescent structures in sometypes of tissue, it is unclear if these methods can effectively suppress AF across all autofluorescent structures within the myocardium. Here, we quantitatively evaluated the performance of several commonly used quenching treatments on formaldehyde-fixed myocardial samples, including 0.3 M glycine, 0.3% Sudan Black B (SBB), 0.1% and 1% sodium borohydride (NaBH4), TrueVIEW® and TrueBlack®. We further assessed their quenching performance by employing the pre-treatment and post-treatment protocols, designed to cover two common IF staining scenarios where buffers contained detergents or not. The results suggest that SBB and TrueBlack® outperform other reagents in AF suppression on formaldehyde-fixed myocardial samples in both protocols. Furthermore, we inspected the quenching performance of SBB and TrueBlack® on major autofluorescent myocardial structures and evaluated their influence on IF imaging. The results suggest that SBB outperforms TrueBlack® in quenching major autofluorescent structures, while TrueBlack® excels in preserving IF labeling signal. Surprisingly, we found the treatment of NaBH4 increased AF signal and enhanced the AF contrast of major autofluorescent structures. This finding suggests that NaBH4 has the potential to act as an AF enhancer and may facilitate the interpretation of myocardial structures without the need for counterstaining.

[Clinical study of intercondylar fossa formation to prevent intercondylar fossa impingement after high tibia osteotomy].

OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION: Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.

Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases.

The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases.

Mitogenomic evolutionary rates in bilateria are influenced by parasitic lifestyle and locomotory capacity.

The evidence that parasitic animals exhibit elevated mitogenomic evolutionary rates is inconsistent and limited to Arthropoda. Similarly, the evidence that mitogenomic evolution is faster in species with low locomotory capacity is limited to a handful of animal lineages. We hypothesised that these two variables are associated and that locomotory capacity is a major underlying factor driving the elevated rates in parasites. Here, we study the evolutionary rates of mitogenomes of 10,906 bilaterian species classified according to their locomotory capacity and parasitic/free-living life history. In Bilateria, evolutionary rates were by far the highest in endoparasites, much lower in ectoparasites with reduced locomotory capacity and free-living lineages with low locomotory capacity, followed by parasitoids, ectoparasites with high locomotory capacity, and finally micropredatory and free-living lineages. The life history categorisation (parasitism) explained ≈45%, locomotory capacity categorisation explained ≈39%, and together they explained ≈56% of the total variability in evolutionary rates of mitochondrial protein-coding genes in Bilateria. Our findings suggest that these two variables play major roles in calibrating the mitogenomic molecular clock in bilaterian animals.

The role of murine M1 macrophages from different sources in unilateral ureteral obstruction.

Introduction: The unilateral ureteral obstruction (UUO) model is the most extensively used model to investigate chronic renal fibrosis. Macrophages play a critical role in the UUO model. We aimed to analyze the phenotype of macrophages from different sources activated in vitro and explore the role of M1 macrophages from various sources in UUO. Material and methods: C57BL/6 mice were randomly allocated to five different groups (n = 5 per group): the sham-operated control group, PBS-treated (UUO + PBS) group, bone marrow-derived M1 macrophage-treated (UUO + BM1) group, peritoneal M1 macrophage-treated (UUO + PM1) group, and splenic M1 macrophage-treated (UUO + SPM1) group. After M1 macrophages were injected into the tail vein of UUO-treated mice, renal fibrosis indexes were determined using HE, Masson staining, and α-SMA. Results: Compared to those in the UUO + PBS group, the pathological changes were much more severe in the UUO + BM1, UUO + PM1, and UUO + SPM1 groups. Compared to that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1 group, the collagen area in the UUO + PM1 group was higher at post-UUO day 5 (p < 0.01). The expression of α-SMA in the UUO + PM1 group was higher than that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1group (p < 0.001). Conclusions: The M1 macrophages cultured in vitro were reinjected into mice and aggravated kidney injury and fibrosis. Compared with BM1 and SPM1, PM1 demonstrated a stronger effect on inducing renal injury and fibrosis.

Applications of Laser Speckle Contrast Imaging Technology in Dermatology.

Laser speckle contrast imaging or laser speckle imaging (LSI) is a noninvasive imaging technology that can detect areas of dynamic perfusion or vascular flow. Thus, LSI has shown increasing diagnostic utility in various pathologies and has been employed for intraoperative, postoperative, and long-term monitoring in many medical specialties. Recently, LSI has gained traction in clinical dermatology because it can be effective in the assessment of pathologies that are associated with increased perfusion and hypervascularity compared with that of normal tissue. To date, LSI has been found to be highly accurate in monitoring skin graft reperfusion, determining the severity of burns, evaluating neurosurgical revascularization, assessing persistent perfusion in capillary malformations after laser therapy, and differentiating malignant and benign skin lesions. LSI affords the advantage of noninvasively assessing lesions before more invasive methods of diagnosis, such as tissue biopsy, while remaining inexpensive and exhibiting no adverse events to date. However, potential obstacles to its clinical use include tissue movement artifact, primarily qualitative data, and unclear impact on clinical practice given the lack of superiority data compared with the current standard-of-care diagnostic methods. In this review, we discuss the clinical applications of LSI in dermatology for use in the diagnosis and monitoring of vascular, neoplastic, and inflammatory skin conditions.