SPMLD: A skin pathological image dataset for non-melanoma with detailed lesion area annotation.

Skin tumors are the most common tumors in humans and the clinical characteristics of three common non-melanoma tumors (IDN, SK, BCC) are similar, resulting in a high misdiagnosis rate. The accurate differential diagnosis of these tumors needs to be judged based on pathological images. However, a shortage of experienced dermatological pathologists leads to bias in the diagnostic accuracy of these skin tumors in China. In this paper, we establish a skin pathological image dataset, SPMLD, for three non-melanoma to achieve automatic and accurate intelligent identification for them. Meanwhile, we propose a lesion-area-based enhanced classification network with the KLS module and an attention module. Specifically, we first collect thousands of H&E-stained tissue sections from patients with clinically and pathologically confirmed IDN, SK, and BCC from a single-center hospital. Then, we scan them to construct a pathological image dataset of these three skin tumors. Furthermore, we mark the complete lesion area of the entire pathology image to better learn the pathologist's diagnosis process. In addition, we applied the proposed network for lesion classification prediction on the SPMLD dataset. Finally, we conduct a series of experiments to demonstrate that this annotation and our network can effectively improve the classification results of various networks. The source dataset and code are available at https://github.com/efss24/SPMLD.git.

The genome assembly of Carex breviculmis provides evidence for its phylogenetic localization and environmental adaptation.

Carex breviculmis is a perennial herb with good resistance and is widely used for forage production and turf management. We assembled the genome of 469.01 Mb, revealing 37,372 genes with a BUSCO completeness score of 99.0%. The genome comprises 52.03% repetitive sequences, primarily influenced by recent LTR insertions that have contributed to its expansion. Phylogenetic analysis suggested that C. breviculmis diverged from C. littledalei approximately 6.61 Mya. Investigation into repetitive sequences and expanded gene families (EGFs) highlighted a rapid expansion of tandem duplicate (TD) genes, particularly in areas related to sugar metabolism, various amino acid synthesis, and phenylpropanoid biosynthesis. Additionally, our analysis identified crucial genes involved in secondary metabolic pathways such as glycolysis, phenylpropanoid biosynthesis, and amino acid metabolism, which have undergone positive selection. We reconstructed the sucrose metabolic pathway and identified significant gene expansions, included 16 INV, 9 SPS, and 12 SuSy genes associated with sucrose metabolism, showed varying levels of expansion. In summary, the expansion of these genes, coupled with subsequent positive selection, contributed to C. breviculmis' ability to adapt to environmental stressors. This study lays the foundation for future research on the evolution of Carex plants, their environmental adaptations, and potential genetic breeding.

Comparative Analysis of Chloroplast Genome of Meconopsis (Papaveraceae) Provides Insights into Their Genomic Evolution and Adaptation to High Elevation.

The Meconopsis species are widely distributed in the Qinghai-Tibet Plateau, Himalayas, and Hengduan Mountains in China, and have high medicinal and ornamental value. The high diversity of plant morphology in this genus poses significant challenges for species identification, given their propensity for highland dwelling, which makes it a question worth exploring how they cope with the harsh surroundings. In this study, we recently generated chloroplast (cp) genomes of two Meconopsis species, Meconopsis paniculata (M. paniculata) and M. pinnatifolia, and compared them with those of ten Meconopsis cp genomes to comprehend cp genomic features, their phylogenetic relationships, and what part they might play in plateau adaptation. These cp genomes shared a great deal of similarities in terms of genome size, structure, gene content, GC content, and codon usage patterns. The cp genomes were between 151,864 bp and 154,997 bp in length, and contain 133 predictive genes. Through sequence divergence analysis, we identified three highly variable regions (trnD-psbD, ccsA-ndhD, and ycf1 genes), which could be used as potential markers or DNA barcodes for phylogenetic analysis. Between 22 and 38 SSRs and some long repeat sequences were identified from 12 Meconopsis species. Our phylogenetic analysis confirmed that 12 species of Meconopsis clustered into a monophyletic clade in Papaveraceae, which corroborated their intrageneric relationships. The results indicated that M. pinnatifolia and M. paniculata are sister species in the phylogenetic tree. In addition, the atpA and ycf2 genes were positively selected in high-altitude species. The functions of these two genes might be involved in adaptation to the extreme environment in the cold and low CO2 concentration conditions at the plateau.

Study of melanocyte density and epidermal thickness in vulvar lichen sclerosus lesions.

OBJECTIVE: This study aimed to analyze changes in melanocyte density and epidermal thickness in vulvar lichen sclerosus (VLS). METHODS: Vulvar skin tissues were collected from 15 VLS female patients in Beijing Hospital, classified into early (n = 7) and late VLS (n = 8) groups according to pathological manifestations. Melanocyte density and full epidermal and cell-layer (from the bottom of the stratum corneum to that of the basal layer) thickness were calculated using an image analysis software. The control group was normal vulvar skin tissues from 15 females after plastic surgery. RESULTS: The early VLS (0.170 ± 0.071 µm) and late VLS (0.110 ± 0.035 µm) groups had significantly lower densities of epidermal melanocytes than the control group (0.275 ± 0.036) (F = 36.426, P < 0.001). The cell-layer thickness did not differ between the early VLS (154.603 ± 121.984 µm) and control (176.974 ± 80.296 µm) groups (P = 0.899) but significantly decreased in the late VLS group (83.455 ± 37.129 µm) compared to the control group (P = 0.003). CONCLUSIONS: Melanocyte density decreased in early and late VLS. The full epidermal and cell-layer thickness did not significantly change in early VLS, but the cell-layer thickness decreased in late VLS.

Functional regulation of an ancestral RAG transposon ProtoRAG by a trans-acting factor YY1 in lancelet.

The discovery of ancestral RAG transposons in early deuterostomia reveals the origin of vertebrate V(D)J recombination. Here, we analyze the functional regulation of a RAG transposon, ProtoRAG, in lancelet. We find that a specific interaction between the cis-acting element within the TIR sequences of ProtoRAG and a trans-acting factor, lancelet YY1-like (bbYY1), is important for the transcriptional regulation of lancelet RAG-like genes (bbRAG1L and bbRAG2L). Mechanistically, bbYY1 suppresses the transposition of ProtoRAG; meanwhile, bbYY1 promotes host DNA rejoins (HDJ) and TIR-TIR joints (TTJ) after TIR-dependent excision by facilitating the binding of bbRAG1L/2 L to TIR-containing DNA, and by interacting with the bbRAG1L/2 L complex. Our data thus suggest that bbYY1 has dual functions in fine-tuning the activity of ProtoRAG and maintaining the genome stability of the host.

A Possible Role of Crustacean Cardioactive Peptide in Regulating Immune Response in Hepatopancreas of Mud Crab.

Crustacean cardioactive peptide (CCAP), a cyclic amidated non-apeptide, is widely found in arthropods. The functions of CCAP have been revealed to include regulation of heart rate, intestinal peristalsis, molting, and osmotic pressure. However, to date, there has not been any report on the possible involvement of CCAP in immunoregulation in crustaceans. In this study, a CCAP precursor (designated as Sp-CCAP) was identified in the commercially important mud crab Scylla paramamosain, which could be processed into four CCAP-associated peptides and one mature peptide (PFCNAFTGC-NH2). Bioinformatics analysis indicated that Sp-CCAP was highly conserved in crustaceans. RT-PCR results revealed that Sp-CCAP was expressed in nerve tissues and gonads, whereas the Sp-CCAP receptor gene (Sp-CCAPR) was expressed in 12 tissues of S. paramamosain, including hepatopancreas. In situ hybridization further showed that an Sp-CCAPR-positive signal is mainly localized in the F-cells of hepatopancreas. Moreover, the mRNA expression level of Sp-CCAPR in the hepatopancreas was significantly up-regulated after lipopolysaccharide (LPS) or polyriboinosinic polyribocytidylic acid [Poly (I:C)] challenge. Meanwhile, the mRNA expression level of Sp-CCAPR, nuclear transcription factor NF-κB homologs (Sp-Dorsal and Sp-Relish), member of mitogen-activated protein kinase (MAPK) signaling pathway (Sp-P38), pro-inflammatory cytokines factor (Sp-TNFSF and Sp-IL16), and antimicrobial peptide (Sp-Lysozyme, Sp-ALF, Sp-ALF4, and Sp-ALF5) in the hepatopancreas were all up-regulated after the administration of synthetic Sp-CCAP mature peptide both in vivo and in vitro. The addition of synthetic Sp-CCAP mature peptide in vitro also led to an increase in nitric oxide (NO) concentration and an improved bacterial clearance ability in the hepatopancreas culture medium. The present study suggested that Sp-CCAP signaling system might be involved in the immune responses of S. paramamosain by activating immune molecules on the hepatopancreas. Collectively, our findings shed new light on neuroendocrine-immune regulatory system in arthropods and could potentially provide a new strategy for disease prevention and control for mud crab aquaculture.

Functional requirement of terminal inverted repeats for efficient ProtoRAG activity reveals the early evolution of V(D)J recombination.

The discovery of ProtoRAG in amphioxus indicated that vertebrate RAG recombinases originated from an ancient transposon. However, the sequences of ProtoRAG terminal inverted repeats (TIRs) were obviously dissimilar to the consensus sequence of mouse 12/23RSS and recombination mediated by ProtoRAG or RAG made them incompatible with each other. Thus, it is difficult to determine whether or how 12/23RSS persisted in the vertebrate RAG system that evolved from the TIRs of ancient RAG transposons. Here, we found that the activity of ProtoRAG is highly dependent on its asymmetric 5'TIR and 3'TIR, which are composed of conserved TR1 and TR5 elements and a partially conserved TRsp element of 27/31 bp to separate them. Similar to the requirements for the recombination signal sequences (RSSs) of RAG recombinase, the first CAC in TR1, the three dinucleotides in TR5 and the specific length of the partially conserved TRsp are important for the efficient recombination activity of ProtoRAG. In addition, the homologous sequences flanking the signal sequences facilitate ProtoRAG- but not RAG-mediated recombination. In addition to the diverged TIRs, two differentiated functional domains in BbRAG1L were defined to coordinate with the divergence between TIRs and RSSs. One of these is the CTT* domain, which facilitates the specific TIR recognition of the BbRAGL complex, and the other is NBD*, which is responsible for DNA binding and the protein stabilization of the BbRAGL complex. Thus, our findings reveal that the functional requirement for ProtoRAG TIRs is similar to that for RSS in RAG-mediated recombination, which not only supports the common origin of ProtoRAG TIRs and RSSs from the asymmetric TIRs of ancient RAG transposons, but also reveals the development of RAG and RAG-like machineries during chordate evolution.

Topical photodynamic therapy with 5-aminolevulinic acid for cervical high-risk HPV infection.

OBJECTIVE: To investigate the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for cervical high-risk HPV (HR-HPV) infection. METHODS: In this prospective study, a total of 76 patients with persistent cervical HR-HPV infection were randomly divided into two groups. The treatment group (39 patients) received three treatments of ALA-PDT at two-week intervals. The control group (37 patients) received no treatment. All patients were followed up for 9 months. Hybrid Capture HPV DNA Assay and ThinPrep cytology test (TCT) were performed for both groups. Patients with abnormal TCT results received colposcopic biopsy before treatment and during follow-ups. RESULTS: HR-HPV remission rates were 64.10% (25/39) in the treatment group and 24.32% (9/37) in the control group at 3 month follow-up. Complete remission rates were 76.92% (30/39) and 32.40% (12/37), respectively, in the two groups at 9 month follow-up. There was a statistically significant difference between the two groups (P<0.01). Conversion rates of abnormal TCT results were 81.81% (9/11) in the treatment group and 12.50% (1/8) in the control group at 3 months, and 90.90% (10/11) and 25.00% (2/8), respectively, at 9 months. Five of six patients with CIN I in the treatment group and no patients in the control group achieved complete response at 9 months. There was a statistically significant difference between the two groups (P<0.01). CONCLUSION: Topical ALA-PDT is an effective, safe and well tolerated treatment for cervical HR-HPV infection.

Clinical and histopathological characteristics of basal cell carcinoma in Chinese patients.

BACKGROUND: The clinical and histopathological characteristics of basal cell carcinoma (BCC) have been relatively well studied in Caucasian population. To characterize BCC in Chinese population, we analyzed the association of the histopathological subtypes with gender, age and anatomical location in this study. METHODS: The clinical and histopathological data of 243 BCC cases diagnosed at three hospitals in Beijing from January 2000 to April 2009 were reviewed retrospectively. Gender, age, location and histopathological subtype were analyzed. RESULTS: Among 243 patients enrolled, 118 were males and 125 were females. The male/female ratio was 0.94:1. The mean age was (65.16 ± 12.62) years old. The head and neck were the most common sites of BCC (77.4%). Of the BCCs, 53.9% were nodular, 18.9% superficial and 18.5% infiltrative-morphoeic. The nodular, infiltrative-morphoeic and micronodular subtypes were predominant located on the head and neck, whereas the trunk was the most common location for the superficial subtype (P < 0.05). The age at first presentation for females was lower than that for males (P < 0.05). The age at first presentation for the superficial BCCs was younger than the non-superficial subtypes (P < 0.05). Women with superficial BCC subtype visited hospital earlier than men (P < 0.05). CONCLUSIONS: Consistent with previous reports in Caucasian patient, our study find that different histopathological subtypes of BCC has distinct clinical features. It is speculated that the mechanisms underlining the pathogenesis of the superficial BCC may be different than those of non-superficial subtypes of BCC.