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Abstract Although there is an association between abdominal aortic aneurysm (AAA) and circulating immune cell phenotypes, the exact causal relationship remains unclear. This study aimed to explore the causal relationships between immune cell phenotypes and AAA risk using a bidirectional two-sample Mendelian randomization approach. Data from genome-wide association studies pertaining to 731 immune cell traits and AAA were systematically analyzed. Using strict selection criteria, we identified 339 immune traits that are associated with at least 3 single nucleotide polymorphisms. A comprehensive MR analysis was conducted using several methods including Inverse Variance Weighted, Weighted Median Estimator, MR-Egger regression, Weighted Mode, and Simple Median methods. CD24 on switched memory cells (OR = 0.922, 95% CI 0.914–0.929, P = 2.62e−79) at the median fluorescence intensities level, and SSC-A on HLA-DR + natural killer cells (OR = 0.873, 95% CI 0.861–0.885, P = 8.96e−81) at the morphological parameter level, exhibited the strongest causal associations with AAA. In the reverse analysis, no significant causal effects of AAA on immune traits were found. The study elucidates the causal involvement of multiple circulating immune cell phenotypes in AAA development, signifying their potential as diagnostic markers or therapeutic targets. These identified immune traits may be crucial in modulating AAA-related inflammatory pathways.

Abstract Purpose To evaluate the predictors for short and long term urinary continence (UC) recovery after laparoscopic radical prostatectomy (LRP) from clinical and oncological variables. Methods We retrospectively collected data from 142 prostate cancer patients who underwent LRP between September 2014 and June 2021 at a tumor specialist diagnosis and treatment center in China. The rate of post-prostatectomy incontinence (PPI) was evaluated from immediate and at 3, 6 and 12 mo after LRP, and UC was defined as the use of no or one safety pad. Sixteen clinical and oncological variables were analyzed by univariate and multivariate regression analysis to determine whether they were associated with short (3 mo) or long term (12 mo) UC recovery after LRP. Results After eliminating patients who were lost to follow-up, 129 patients were eventually included. The mean ± SD age was 68 ± 6.3 years. The UC rates of immediate, 3, 6 and 12 mo after the operation were 27.9%, 54.3%, 75.2% and 88.4%, respectively. Multivariate analyses revealed that membranous urethral length (MUL) was a protective predictor of UC after catheter extraction(P

Vessel density within tumor tissues strongly correlates with tumor proliferation and serves as a critical marker for tumor grading. Recognition of vessel density by pathologists is subject to a strong inter-rater bias, thus limiting its prognostic value. There are many challenges in the task of object detection in pathological images, including complex image backgrounds, dense distribution of small targets, and insignificant differences between the features of the target to be detected and the image background. To address these problems and thus help physicians quantify blood vessels in pathology images, we propose Pathological Images-YOLO (PI-YOLO), an enhanced detection network based on YOLOv7. PI-YOLO incorporates the BiFormer attention mechanism, enhancing global feature extraction and accelerating processing for regions with subtle differences. Additionally, it introduces the CARAFE upsampling module, which optimizes feature utilization and information retention for small targets. Furthermore, the GSConv module improves the ELAN module, reducing model parameters and enhancing inference speed while preserving detection accuracy. Experimental results show that our proposed PI-YOLO network has higher detection accuracy compared to Faster-RCNN, SSD, RetinaNet, YOLOv5 network, and the latest YOLOv7 network, with a mAP value of 87.48%, which is 2.83% higher than the original model. We also validated the performance of this network on the ICPR 2012 mitotic dataset with an F1 value of 0.8678, outperforming other methods, demonstrating the advantages of our network in the task of target detection in complex pathology images.

Abstract Background Several studies have investigated the correlation between phosphodiesterase 4D (PDE4D) single nucleotide polymorphism (SNP) rs918592 and the risk of ischemic stroke (IS) in Chinese populations. But the results were inconsistent and inconclusive. Therefore, to resolve this conflict, we conducted a meta-analysis to further elucidate their relationship in Chinese populations. Methods Studies focused on SNP rs918592 and IS risk were electronic searched in the databases of PubMed, Embase, ISI Web of Science, Weipu, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and Wanfang. The association between SNP rs918592 and IS risk was expressed by odds ratio (OR) with its confidence interval (CI). Begg’s and Egger’s linear regression tests were used to assess publication bias. The meta-analysis was performed with STATA 11.0 statistical software. Two online prediction websites (HaploReg and RegulomeDB) were adopted to explore the functions of SNP rs918592. Results The meta-analysis ultimately included 10 studies involving 2,348 cases and 2,289 controls. The results showed that there was a significant correlation between SNP rs918592 and IS risk in Chinese individuals. The G allele had reduced risk of developing IS compared to the A allele (OR 0.83, 95% CI 0.74–0.95, P = 0.005). HaploReg and RegulomeDB analyses suggested that SNP rs918592 and its strongly linked SNPs (e.g. rs34168777) might have regulatory functions. Conclusion This study shows that SNP rs918592 in PDE4D may be a contributor of IS risk in Chinese populations. It offers a good answer for the association of PDE4D SNP rs918592 with IS risk in Chinese populations for the first time.

Purpose: Amyopathic dermatomyositis (ADM) is a rare, idiopathic, connective tissue disease and melanoma differentiation-associated protein 5 (MDA5) antibody-positive ADM is more treatment-resistant, especially in patients with interstitial lung disease (ILD). The purpose of this article is to report a case of anti-MDA5-positive ADM successfully treated with JAK inhibitor Upadacitinib.Materials and methods: A 35-year-old Chinese woman presented with recurrent itchy erythema on her face and scalp for 4 years. Upon examination, there were heliotrope erythema and eyelid edema, reddish rash on neck and scalp. Biopsy of the lesions was consistent with DM and a line blot assay confirmed the presence of anti-MDA5 antibodies. This patient was treated with oral Upadacitinib at a dosage of 30 mg daily.Results: After 6 weeks of treatment, she achieved complete clinical remission with no reported side effects or instances of relapse. The antibody titer of anti-MDA5 was also decreased.Conclusions: Upadacitinib may be a potential drug candidate in patients with treatment-resistant ADM, especially in cases with refractory cutaneous conditions.

Background Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.Methods We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).Results Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.Conclusion Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.Trial registration number Chinese Clinical Trial Registry, ChiCTR1900023277.

Abstract Introduction Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. Methods A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. Results Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. Conclusion This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

Abstract Objective The authors investigated the expression of IgG4 and IgG in cutaneous Rosai-Dorfman Disease (CRDD) to further improve the understanding of this disease. Methods The authors retrospectively reviewed the clinicopathological features of 23 CRDD patients. The authors diagnosed CRDD by the presence of emperipolesis and immunohistochemical (IHC) staining of histiocytes consisting of S-100(+)/CD68(+)/CD1a(-) cells. The expressions of IgG and IgG4 in cutaneous specimens were assessed by IHC (EnVision) and quantitatively calculated by a medical image analysis system. Results All 23 patients, including 14 males and 9 females, were confirmed to have CRDD. Their ages ranged from 17 to 68 years (mean 47.91 ± 14.16). The most frequently affected skin regions were the face, followed by the trunk, ears, neck, limbs, and genitals. In 16 of these cases, the disease presented as a single lesion. IHC staining of sections showed that IgG was positive (≥ 10 cells/High-Power Field [HPF]) in 22 cases, while IgG4 was positive (≥ 10 cells/HPF) in 18 cases. Moreover, the IgG4/IgG proportion ranged from 1.7% to 85.7% (mean 29.50 ± 24.67%, median 18.4%) in the 18 cases. Study limitations In the majority of studies, as well as in the current study, the design. RDD is a rare disease, so the sample size is small. In the next studies to come, the authors will expand the sample for multi-center verification and in-depth study. Conclusion The positive rates of IgG4 and IgG and the IgG4/IgG ratio assessed through IHC staining may be important in understanding the pathogenesis of CRDD.

Abstract The green microalga Haematococcus pluvialis can synthesize high amounts of astaxanthin, which is a valuable antioxidant that has been utilized in human health, cosmetics, and aquaculture. To illustrate detailed molecular clues to astaxanthin yield, we performed PacBio HIFI along with Hi-C sequencing to construct an improved chromosome-level haplotypic genome assembly with 32 chromosomes and a genome size of 316.0 Mb. Its scaffold N50 (942.6 kb) and contig N50 (304.8 kb) have been upgraded remarkably from our previous genome draft, and a total of 32,416 protein-coding genes were predicted. We also established a high-evidence phylogenetic tree from seven representative algae species, with the main aim to calculate their divergence times and identify expanded/contracted gene families. We also characterized genome-wide localizations on chromosomes of some important genes such as five BKTs (encoding beta-carotene ketolases) that are putatively involved in astaxanthin production. In summary, we reported the first chromosome-scale map of H. pluvialis, which provides a valuable genetic resource for in-depth biomedical investigations on this momentous green alga and commercial astaxanthin bioproduction.

Abstract Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. Methods Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. Results Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. Conclusions Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Abstract Strabismus is a common ophthalmologic disease that affects approximately 1.19% to 5.0% of children; however if the disease is detected early it can be treated effectively. Generally, the automatic detection of strabismus is usually performed only by a single feature, which is, with image deep features or ratio features. However, the accuracy of a strabismus diagnosis with a single feature is unreliable. This study aims to develop an intelligent strabismus detection model driven by corneal light reflection photographs to automatically detect children's strabismus. The proposed multi‐feature fusion model (MFFM) improves the detection performance by fusing the deep features and ratio features extracted from the corneal light reflection photographs to identify strabismus. The experimental results demonstrate that our proposed multi‐feature model outperforms all of the single feature models in strabismus detection. The experiments show that the proposed method achieves an accuracy of 97.17%, sensitivity of 96.06%, specificity of 97.79%, and AUC of 0.969 in strabismus detection. Our evidence shows that it greatly improves the performance of strabismus detection.

Abstract Background Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. Methods A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan–Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. Results The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25–5.29, p = 0.01; HR = 2.77, 95% CI 1.22–6.28, p = 0.02; HR = 3.43, 95% CI 1.51–7.82, p

Abstract Background Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases. Methods Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated. Results 92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P

Abstract Breast cancer accounts for the largest number of patients among all cancers in the world. Intervention treatment for early breast cancer can dramatically extend a woman's 5‐year survival rate. However, the lack of public available breast mammography databases in the field of Computer‐aided Diagnosis and the insufficient feature extraction ability from breast mammography limit the diagnostic performance of breast cancer. In this paper, A novel classification algorithm based on Convolutional Neural Network (CNN) is proposed to improve the diagnostic performance for breast cancer on mammography. A multi‐view network is designed to extract the complementary information between the Craniocaudal (CC) and Mediolateral Oblique (MLO) mammographic views of a breast mass. For the different predictions of the features extracted from the CC view and MLO view of the same breast mass, the proposed algorithm forces the network to extract the consistent features from the two views by the cross‐entropy function with an added consistent penalty term. To exploit the discriminative features from the insufficient mammographic images, the authors learnt an encoder in the classification model to learn the invariable representations from the mammographic breast mass by Supervised Contrastive Learning (SCL) to weaken the side effect of colour jitter and illumination of mammographic breast mass on image quality degradation. The experimental results of all the classification algorithms mentioned in this paper on Digital Database for Screening Mammography (DDSM) illustrate that the proposed algorithm greatly improves the classification performance and diagnostic speed of mammographic breast mass, which is of great significance for breast cancer diagnosis.

Farmers must accurately and promptly identify sugarcane leaf diseases with identical symptoms. RGB images have a beneficial function in disease identification. Nevertheless, complex backgrounds and identical symptoms can significantly reduce the recognition accuracy and robustness. To overcome these challenges, the SLViT hybrid network is presented, in which the transformer encoder is converted to a flexible plug-in (LViT) that is subsequently integrated into several locations of a lightweight CNN architecture (SHDC). SLViT is initially trained on the publicly available disease dataset Plant Village before being moved to the self-created sugarcane leaf disease dataset SLD10k, which consists of seven classes and 10,309 images. The ablation experiments demonstrate that all the adjustments to SLViT have contributed positively to its overall performance. SLViT outperforms six SOTA models and three custom-designed leaf-disease recognition models on Plant Village in terms of speed (1,832 FPS), weight (2 MB), consumption (50 M), and precision (98.84 %). SLViT also outperformed MobileNetV3_small on the SLD10k dataset with an accuracy bonus of 1.87 % and a size reduction of 66.3 %. The experiment also reveals that SLViT has absorbed the advantages of both the lightweight CNN and the noise-resistant transformer. This study demonstrates the applicability of SLViT for sugarcane leaf diagnosis in the field.

Background: With the rapid development of high-throughput sequencing technology and the explosive growth of genomic data, storing, transmitting and processing massive amounts of data has become a new challenge. How to achieve fast lossless compression and decompression according to the characteristics of the data to speed up data transmission and processing requires research on relevant compression algorithms.Methods: In this paper, a compression algorithm for sparse asymmetric gene mutations (CA_SAGM) based on the characteristics of sparse genomic mutation data was proposed. The data was first sorted on a row-first basis so that neighboring non-zero elements were as close as possible to each other. The data were then renumbered using the reverse Cuthill-Mckee sorting technique. Finally the data were compressed into sparse row format (CSR) and stored. We had analyzed and compared the results of the CA_SAGM, coordinate format (COO) and compressed sparse column format (CSC) algorithms for sparse asymmetric genomic data. Nine types of single-nucleotide variation (SNV) data and six types of copy number variation (CNV) data from the TCGA database were used as the subjects of this study. Compression and decompression time, compression and decompression rate, compression memory and compression ratio were used as evaluation metrics. The correlation between each metric and the basic characteristics of the original data was further investigated.Results: The experimental results showed that the COO method had the shortest compression time, the fastest compression rate and the largest compression ratio, and had the best compression performance. CSC compression performance was the worst, and CA_SAGM compression performance was between the two. When decompressing the data, CA_SAGM performed the best, with the shortest decompression time and the fastest decompression rate. COO decompression performance was the worst. With increasing sparsity, the COO, CSC and CA_SAGM algorithms all exhibited longer compression and decompression times, lower compression and decompression rates, larger compression memory and lower compression ratios. When the sparsity was large, the compression memory and compression ratio of the three algorithms showed no difference characteristics, but the rest of the indexes were still different.Conclusion: CA_SAGM was an efficient compression algorithm that combines compression and decompression performance for sparse genomic mutation data.

Abstract Cardiac arrest is a fatal and urgent disease in humans. A high‐quality electrocardiogram (ECG) has a positive guide to the success of defibrillation and resuscitation. However, because of artificial motion interference and ambient noise, reliable ECG signals can be obtained only during chest compression (CC) pauses. To address this issue, the adaptive recursive least squares (RLS) denoising approach is proposed. First, the ECG signals of porcine are divided into three groups: CC, without CC, and both with and without CC. Then, five Gaussian noises with different signals‐to‐noise ratios (SNR) and five noises with different distribution types are added, respectively. Furthermore, RLS is compared with six other different denoising approaches. Experimental results demonstrate significant differences between RLS and the other six algorithms in main metrics. SNR and related factors are larger, while the root mean square error is smaller. In conclusion, RLS can significantly eliminate many types of ambient noise, and improve the quality of ECG signals during cardiopulmonary resuscitation.

Abstract Tuberculosis is a chronic infectious disease that gradually poses a certain threat to public health and economic growth. Tuberculosis typically affects the lungs, pleura, and lymph nodes and rarely the skin. Cutaneous tuberculosis manifesting as ulcerated lesions is also rare and often misdiagnosed and missed by clinicians. Here, the authors report a 29-year-old female patient presenting a vulvar ulcer for 10 months, accompanied by irregular menstruation and increased vaginal secretions. After a skin biopsy and endometrial PCR testing, it was finally diagnosed as vulvar ulcerative cutaneous tuberculosis secondary to genital tuberculosis. Antituberculosis treatment was effective. Cutaneous tuberculosis is called a great imitator. In order to facilitate the diagnosis and treatment of tuberculosis by clinicians, the authors systematically reviewed this disease as well.

Lip verrucous carcinoma is a rare low-grade neoplasm, with an unsightly appearance and locally aggressive nature. Treatment of verrucous carcinoma is as yet challenging, no well-defined guidelines for effective and safe management of this disease are available. A case of a patient with a huge verrucous carcinoma of the lower lip successfully treated by surgical excision and double Abbe flap reconstruction technique is presented, and striking features of lip locations of this tumor as well as their management are discussed.

Abstract The rapid estimation of the accurate disparity between pixels is the goal of stereo matching. However, it is very difficult for the 3D labels‐based methods due to huge search space of 3D labels, especially for high‐resolution images. In this paper, a novel superpixel cut‐based method is proposed, in an attempt to get the accurate disparity map efficiently, including the multi‐layer superpixel optimization and iteractive local α‐expansion in parallel. As for the multi‐layer superpixel optimization, feature point optimization is designed to get accurate candidate labels that are set for most pixels using non‐local cost aggregation strategy and update per‐pixel labels of the corresponding superpixels from the candidate label sets on the small‐size superpixel layer, and then update the middle to large‐size superpixel layers progressively using non‐local cost aggregation strategy. In order to provide more prior information to identify weak texture and textureless regions in non‐local cost aggregation, the weight combination of “intensity + gradient + binary image” is proposed for constructing an optimal minimum spanning tree (MST) to calculate the aggregated matching cost and obtain the labels of minimum aggregated matching cost. Moreover, the local patch surrounding the corresponding superpixels is designed to accelerate superpixel optimization in parallel, and a neighborhood structure is presented to optimize the algorithm in this study, including superpixel neighborhood and patch neighborhood. As for the iteractive local α‐expansion, three layers of patch structure corresponding to the superpixel neighborhood structure is proposed for optimizing the algorithm in this study. The experimental results show that higher accuracy could be achieved via the method in this study compared with some known state‐of‐the‐art stereo methods on KITTI 2015 and Middlebury benchmark V3, which are the standard benchmarks for testing the stereo matching methods.

Chlamydomonas reinhardtii is a photosynthetic eukaryote showing great industrial potential. The synthesis and in vivo function of the artificial C. reinhardtii genome not only promotes the development of synthetic biology technology but also supports industries that utilize this algae. Mitochondrial genome (MtG) is the smallest and simplest genome of C. reinhardtii that suits synthetic exploration. In this article, we designed and assembled a synthetic mitochondria left arm (syn-LA) genome sharing >92% similarity to the original mitochondria genome (OMtG) left arm, transferred it into the respiratory defect strain cc-2654, screened syn-LA containing transformants from recovered dark-growth defects using PCR amplification, verified internal function of syn-LA via western blot, detected heteroplasmic ratio of syn-LA, tried promoting syn-LA into homoplasmic status with paromomycin stress, and discussed the main limitations and potential solutions for this area of research. This research supports the functionalization of a synthetic mitochondrial genome in living cells. Although further research is needed, this article nevertheless provides valuable guidance for the synthesis of eukaryotic organelle genomes and opens possible directions for future research.

Context Pogostone possesses various pharmacological activities, which makes it widely used in the clinic. Its effect on the activity of cytochrome P450 enzymes (CYP450s) could guide its clinical combination. Objective To investigate the effect of pogostone on the activity of human CYP450s. Materials and methods The effect of pogostone on the activity of CYP450s was evaluated in human liver microsomes (HLMs) compared with blank HLMs (negative control) and specific inhibitors (positive control). The corresponding parameters were obtained with 0–100 μM pogostone and various concentrations of substrates. Results Pogostone was found to inhibit the activity of CYP3A4, 2C9, and 2E1 with the IC50 values of 11.41, 12.11, and 14.90 μM, respectively. The inhibition of CYP3A4 by pogostone was revealed to be performed in a non-competitive and time-dependent manner with the Ki value of 5.69 μM and the KI/Kinact value of 5.86/0.056/(μM/min). For the inhibition of CYP2C9 and 2E1, pogostone acted as a competitive inhibitor with the Ki value of 6.46 and 7.67 μM and was not affected by the incubation time. Discussion and conclusions The inhibitory effect of pogostone on the activity of CYP3A4, 2C9, and 2E1 has been disclosed in this study, implying the potential risk during the co-administration of pogostone and drugs metabolized by these CYP450s. The study design provides a reference for further in vivo investigations to validate the potential interaction.

In eukaryotes, mRNA metabolism requires a sophisticated signaling system. Recent studies have suggested that polyadenylate tail may play a vital role in such a system. The poly(A) tail used to be regarded as a common modification at the 3′ end of mRNA, but it is now known to be more than just that. It appears to act as a platform or hub that can be understood in two ways. On the one hand, polyadenylation and deadenylation machinery constantly regulates its dynamic activity; on the other hand, it exhibits the ability to recruit RNA-binding proteins and then interact with diverse factors to send various signals to regulate mRNA metabolism. In this paper, we outline the main complexes that regulate the dynamic activities of poly(A) tails, explain how these complexes participate polyadenylation/deadenylation process and summarize the diverse signals this hub emit. We are trying to make a point that the poly(A) tail can metaphorically act as a “flagman” who is supervised by polyadenylation and deadenylation and sends out signals to regulate the orderly functioning of mRNA metabolism.

There are inconsistencies in the published findings on the association of variant rs556621 in an intergenic region on Chromosome 6p21.1 with the risk of developing ischemic stroke (IS) and a major IS subtype (large artery atherosclerosis, LAA) in Chinese populations. We conducted a meta-analysis to evaluate the association of variant rs556621 with IS/LAA risk using ten studies involving 3644 IS cases and 3692 controls (including seven studies involving 2268 LAA cases and 2268 controls) from China. The AA genotype increased IS risk (AA versus CC: odds ratio [OR] 1.19, 95% confidence interval [CI] 1.03-1.36, P = 0.015; AA versus CA + CC: OR 1.23, 95% CI 1.09-1.39, P = 0.001). Subgroup analysis also suggested that rs556621 contributed to the risk of IS both in Chinese Han and the miscellaneous group. However, these results were stable in Chinese Han but not in the miscellaneous group. When restricting our analysis to the LAA subtype, similar results were obtained. This meta-analysis is the first meta-analysis on the correlation between rs556621 and the susceptibility of IS/LAA and demonstrates that rs556621 is associated with IS/LAA risk in Chinese populations. Further meta-analysis warrants larger well-designed investigations to assess these effects.

Background. Interferon-inducible 44 like (IFI44L) is a newly discovered interferon-induced gene and has been reported to overexpress in systemic lupus erythematosus (SLE). However, little is known about the mechanism and function of IFI44L overexpression in SLE. In this study, we aimed to investigate the epigenetic mechanism of IFI44L overexpression in SLE monocyte and its potential functions contributing to the pathogenesis of SLE. Methods. We collected peripheral blood from 20 SLE patients and 20 healthy controls. Expression of IFI44L in monocytes and effects of different signal transducers and activators of transcription (STAT) pathway inhibitors on IFI44L expression were detected. Recruitment of ten-eleven translocation protein (TET) by STAT and methylation of IFI44L promoter were evaluated. Effects of IFI44L overexpression on the expression of surface markers on monocyte-derived dendritic cells (Mo-DCs) were analyzed. T cell differentiation mediated by Mo-DCs and related cytokines production were also analyzed. Results. Expression level of IFI44L was significantly increased in SLE monocyte. IFI44L expression was decreased most significantly in STAT3 inhibitor compared with other inhibitors. STAT3 regulated IFI44L expression and interacted with TET2 which induced DNA demethylation of IFI44L promoter. Overexpression of IFI44L in monocyte enhanced the maturation and functions of Mo-DC by upregulating costimulatory receptors and inducing Th1/Th17-related cytokines when cocultured with naïve CD4+ T cells. Conclusion. TET2 recruited by STAT3 induces DNA demethylation of IFI44L promoter which promotes IFI44L overexpression in monocyte contributing to the pathogenesis of SLE by enhancing the maturation and functions of Mo-DC. IFI44L is expected to become a new target for treatment of SLE.

Abstract Hidrotic ectodermal dysplasia (HED) is a rare inherited syndrome characterised by nail dystrophy, palmoplantar hyperkeratosis and alopecia. Four mutations (p.G11R, p.A88V, p.V37E and p.D50N) in gap junction beta 6 (GJB6) gene, which codes connexin30 protein, have been found to cause HED in different populations. Here, we reported a big Chinese family in which 24 patients over five generations were suffered with HED. Sequence analysis identified all 24 patients carry a recurrent missense mutation c.263C > T (p.A88V) in GJB6. Our results reveal gene testing of GJB6 is important for diagnosis, prenatal diagnosis and future gene treatment of HED.

Abstract Autosomal recessive congenital ichthyosis (ARCI) is a rare form of keratinization disorder of the skin, which can be caused by mutations in 14 ARCI genes. We present a rare case of ARCI that carried a novel null mutation and a novel splice site mutation in the CYP4F22 gene.

Background: Increased antibiotic resistance is one of the major factors contributing to the failure of H. pylori eradication. This study aimed to compare the efficacy and safety of doxycycline and amoxicillin, both critical components for bismuth-based quadruple therapy, for the first-line treatment of H. pylori-infected duodenal ulcers. Methods: An open, randomized case-controlled, multicenter trial was conducted in seven hospitals in China. A total of 184 eligible participants were divided into an IDFB (ilaprazole 5 mg, doxycycline 100 mg, furazolidone 100 mg, and bismuth 220 mg bid) or IAFB (ilaprazole 5 mg, amoxicillin 1000 mg, furazolidone 100 mg, and bismuth 220 mg bid) group for 14 days. Both groups were administrated with ilaprazole 5 mg qd for another 14 days. The main outcome was an H. pylori eradication rate; secondary outcomes were ulcer healing, relief of symptoms, and incidence of adverse effects. Results: The H. pylori eradication rates were 85.9% (95% CI 78.6–93.9) in the IDFB vs. 84.8% (95% CI 77.3–92.3) in the IAFB group in ITT analysis (p > 0.05), and 92.9% (95% CI 87.4–98.5) vs. and 91.8% (95% CI 85.8–97.7) in PP analysis (p > 0.05). The overall ulcer healing rates of IDFB and IAFB were 79.1% and 84.7% (p > 0.05), both effective in relieving symptoms. Only nine participants had adverse reactions in this trial (4/92 in IDFB and 5/92 in IAFB). Conclusion: A bismuth quadruple regimen containing doxycycline or amoxicillin could be an effective and safe treatment for H. pylori eradication, while doxycycline replacement is an alternative for participants with penicillin allergy.

Since late December 2019, an outbreak of the novel coronavirus disease, which is mainly characterized by pulmonary lesions, has spread quickly worldwide. With the spread of the novel coronavirus, the outpatient lines of hospitals have mostly shut down, which means that routine clinical diagnosis and treatment for autoimmune bullous diseases patients have been disturbed. Due to the serious condition of autoimmune bullous diseases patients, they are prone to immune suppression and circulatory failure, and are more susceptible to infection than healthy individuals. These patients should thus be a priority group for novel coronavirus disease prevention. In this context, the protection and control measures for autoimmune bullous diseases patients against the novel coronavirus are of serious concern. Clinicians should strengthen their communication with patients, pay attention to changes in patients’ conditions, and carefully adjust the treatment strategy, while protecting against the novel coronavirus infection, to ensure the continuity, safety, and effectiveness of autoimmune bullous diseases treatment.

The three-axis coil system is most commonly used in magnetic field measurement. The coil constant is an important parameter. We demonstrate a method to measure the coil constant based on the Larmor frequency. An elliptically polarized light is used to simultaneously excite the spin orientation and spin alignment via synchronous optical pumping. And then the coil system can be calibrated by measuring the magnetic resonance frequency of Bell-Bloom magnetometer. The advantage of this method is that the coil constants of all three directions can be obtained without any active adjustments. It is important for some applications, such as measuring the biological magnetic field with the integrated magnetometer. The method for calibration of a three-axis coil system is experimentally exploited. The experimental results show that the calibration accuracy of pT level can be achieved.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. As psoriasis rarely occurs in nonhuman animals, the lack of an ideal animal model reflecting the histopathological and molecular immunological characteristics of psoriasis remains an urgent issue. In the present study, an imiquimod-induced psoriasis-like dermatitis mouse model was constructed under natural immune conditions and verified by evaluations of the Psoriasis Area and Severity Index (PASI) score and Baker score, H&E staining, immunohistochemical examination of the CD3 and Gr1 levels, measurement of plasmacytoid dendritic cell- (pDC) and Th17-associated cytokine levels, and evaluation of p65 phosphorylation and TLR7 expression. Moreover, rutaecarpine (RUT), the main active ingredient in the traditional Chinese medicine Wu-Zhu-Yu, could improve psoriasis-like dermatitis through effects on pDC- and Th17-associated cytokines through NF-κB and toll-like receptor 7 (TLR7) signaling. Taken together, the imiquimod-induced psoriasis-like dermatitis mouse model can be regarded as an ideal model for evaluating psoriasis pathogenesis and antipsoriatic drugs. We provided theoretical and experimental evidence for the clinical application of RUT in psoriasis.

Two Chinese children presented with relapsing papules, vesicles, ulcers on the face and limbs with systemic symptoms being caused by mosquito bite. Lesion biopsy revealed atypical lymphocyte in the dermis and subcutis. Immunohistochemistry identified cells as positive for CD3, CD45RO, TIA-1 and EBER. Taken together, both the patients were diagnosed with hydroa vacciniforme-like lymphoma. Two patients showed significant improvement in clinical symptoms after being treated with acyclovir, low dose predisone and IFN-α.

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Abstract Disentangling the interactions between cyanobacteria and associated bacterial community is important for understanding the mechanisms that mediate the formation of cyanobacterial blooms in freshwater ecosystems. Despite the fact that a metagenomic approach enables researchers to profile the structure of microbial communities associated with cyanobacteria, reconstructing genome sequences for all members remains inefficient, due to the inherent enormous microbial diversity. Here, we have established a stable coculture system under high salinity, originally from a mixture of an axenic cyanobacterium Synechococcus sp. PCC 7002 and a non-axenic bloom-forming cyanobacterium Microcystis colony. Metagenomic analysis showed that the coculture consists of S. sp. PCC 7002 and two heterotrophic bacteria, designated as Pseudomonas stutzeri TAIHU and Mesorhizobium sp. TAIHU, respectively. And near-complete genome sequences of both bacteria were reconstructed from the metagenomic dataset with an average completeness of 99.8%. Genome-wide pathway analysis revealed that M. sp. TAIHU carried all the genes involved in the de novo biosynthesis of cobalamin, which is required by S. sp. PCC 7002 for growth. To cope with the high salinity in the coculture, experimental evidence demonstrated that S. sp. PCC 7002 would synthesize the compatible solutes including sucrose and glucosylglycerol, which are supposed to be exploited by both heterotrophic bacteria as potential carbon and/or nitrogen sources. Furthermore, the genes encoding for the biosynthesis of the ectoine, another common osmolyte are found exclusively in P. stutzeri TAIHU, while the genes responsible for the catabolism of ectoine and its derives are present only in M. sp. TAIHU. These genomic evidence indicates beneficial interaction between three members in the coculture. Establishment of the coculture system with relative simplicity provides a useful model system for investigating the interspecies interactions, and genome sequences of both bacteria associated with Microcystis bloom described here will facilitate the researcher to elucidate the role of these heterotrophic bacteria in the formation and maintenance of cyanobacterial bloom in freshwater ecosystem.

Optically pumped atomic magnetometers operating in the spin exchange relaxation free (SERF) regime play increasingly important roles in magnetoencephalography measurements. In this application, a multichannel arrangement is necessary. A method to construct the multichannel system is to arrange multiple individual sensor modules, where each sensor module is designed in the one-beam configuration with the necessary magnetic modulation. However, such an arrangement restricts the spatial resolution, affects the uniformity of the sensor characteristics, and increases the system complexity. To address these issues, we developed a compact multichannel pump-probe configuration magnetometer based on a single vapor cell. Each channel of the multichannel system shares the same vapor cell. As a result, the influence of different cells is eliminated. Further, a two-beam configuration with an independent pump and probe beam is introduced. Compared with the one-beam configuration, the two-beam magnetometer achieves a higher sensitivity and does not require extra magnetic modulation. And then the magnetic field crosstalk between adjacent channels can be avoided. A sensitivity of 10 fT/Hz1/2 at 2 Hz is achieved for all channels. Using the compact multichannel magnetometer, an auditory evoked response is clearly observed. If more channels are required, the arrangement based on the single vapor cell configuration can be easily expanded by applying the photodiode with more than four quadrants.

Psoriasis is a common and chronic autoimmune skin disease which affects 2 to 3% of the world population. Abnormal proliferation of human keratinocytes is an important feature of psoriasis, along with local hypoxia and vascular abnormal growth. To leverage recent molecular findings into the personalized treatment of psoriasis, we need a strategy that integrates clinical stratification with molecular phenotyping. MicroRNAs (miRNAs) are a large family of small non-coding RNA which regulates diverse biological process, including cell proliferation, by modulating gene expression at the posttranscriptional level. In the present study, we indicated that miR-150 specifically down-regulated expressed in psoriatic skin lesions, and could inhibit HaCaT cells and primary adult human keratinocytes (HKCs)' proliferation in either normal or hypoxia conditions; by direct targeting, miR-150 could also regulate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA). In addition, we found that HIF-1α and VEGFA were highly expressed in the lesional psoriatic skin compared with the non-lesional psoriatic skin, and negatively correlated with miR-150 expression. Taken together, we indicated miR-150 regulates human keratinocytes' proliferation in hypoxic conditions through targeting HIF-1α and VEGFA in psoriasis for the first time, and provide diagnostic markers and a novel target for psoriasis treatment.