TPMA: A two pointers meta-alignment tool to ensemble different multiple nucleic acid sequence alignments.

Accurate multiple sequence alignment (MSA) is imperative for the comprehensive analysis of biological sequences. However, a notable challenge arises as no single MSA tool consistently outperforms its counterparts across diverse datasets. Users often have to try multiple MSA tools to achieve optimal alignment results, which can be time-consuming and memory-intensive. While the overall accuracy of certain MSA results may be lower, there could be local regions with the highest alignment scores, prompting researchers to seek a tool capable of merging these locally optimal results from multiple initial alignments into a globally optimal alignment. In this study, we introduce Two Pointers Meta-Alignment (TPMA), a novel tool designed for the integration of nucleic acid sequence alignments. TPMA employs two pointers to partition the initial alignments into blocks containing identical sequence fragments. It selects blocks with the high sum of pairs (SP) scores to concatenate them into an alignment with an overall SP score superior to that of the initial alignments. Through tests on simulated and real datasets, the experimental results consistently demonstrate that TPMA outperforms M-Coffee in terms of aSP, Q, and total column (TC) scores across most datasets. Even in cases where TPMA's scores are comparable to M-Coffee, TPMA exhibits significantly lower running time and memory consumption. Furthermore, we comprehensively assessed all the MSA tools used in the experiments, considering accuracy, time, and memory consumption. We propose accurate and fast combination strategies for small and large datasets, which streamline the user tool selection process and facilitate large-scale dataset integration. The dataset and source code of TPMA are available on GitHub (https://github.com/malabz/TPMA).

Postpartum choriocarcinoma - a rare cause of delayed postpartum hemorrhage: Four case reports and literature review.

BACKGROUND: Delayed postpartum hemorrhage is rare, with an incidence of 0.5% to 2.0% in all pregnancies. The most important causes are placental remnants, infections, and placental bed subinvolution. Postpartum choriocarcinoma, a highly malignant complication of pregnancy, is a rare condition that can be easily misdiagnosed as other common causes, such as gestational remnants, and delays the diagnosis. METHODS: Four patients visited our clinic complaining of delayed postpartum hemorrhage, combined with respiratory and neurological symptoms in 2 cases. Two cases were confirmed by histopathological examination and in addition, medical history, elevated human chorionic gonadotropin (hCG) level, and imaging findings help confirm the diagnosis of delayed postpartum hemorrhage caused by postpartum choriocarcinoma in other cases. Individualized combination chemotherapies were prescribed. In the light of massive cerebral metastasis in case 2, intrathecal methotrexate injection combined with whole-brain radiotherapy was prescribed. RESULTS: Due to the absence of routine monitoring of ß-hCG following full-term delivery, there was widespread metastasis at the time of diagnosis. Three patients got complete remission and there is no sign of recurrence. One patient had relapse and widespread metastasis and died at home 6 months after the last chemotherapy. CONCLUSION: It is important to be aware of the possibility of choriocarcinoma in patients with delayed postpartum hemorrhage. Clinicians should improve the recognition of choriocarcinoma following full-term delivery, emphasize the monitoring of ß-hCG, comprehensively analyze the general condition of patients, and conduct standardized and individualized chemotherapy protocols.

Depression-associated gut microbes, metabolites and clinical trials.

Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including Lactobacillus acidophilus and Bifidobacterium longum, and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.

MMiKG: a knowledge graph-based platform for path mining of microbiota-mental diseases interactions.

The microbiota-gut-brain axis denotes a two-way system of interactions between the gut and the brain, comprising three key components: (1) gut microbiota, (2) intermediates and (3) mental ailments. These constituents communicate with one another to induce changes in the host's mood, cognition and demeanor. Knowledge concerning the regulation of the host central nervous system by gut microbiota is fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Such a format hinders the exploration and comprehension of unknown territories or the further advancement of artificial intelligence systems. Hence, we collated crucial information by scrutinizing an extensive body of literature, amalgamated the extant knowledge of the microbiota-gut-brain axis and depicted it in the form of a knowledge graph named MMiKG, which can be visualized on the GraphXR platform and the Neo4j database, correspondingly. By merging various associated resources and deducing prospective connections between gut microbiota and the central nervous system through MMiKG, users can acquire a more comprehensive perception of the pathogenesis of mental disorders and generate novel insights for advancing therapeutic measures. As a free and open-source platform, MMiKG can be accessed at http://yangbiolab.cn:8501/ with no login requirement.

Venous Thromboembolism After COVID-19 Infection Among People With and Without Immune-Mediated Inflammatory Diseases.

Importance: Immune-mediated inflammatory diseases (IMIDs) and COVID-19 are independently associated with venous thromboembolisms (VTEs). Objective: To determine if individuals with IMIDs are at higher risk of VTE following COVID-19 infection compared with individuals without IMIDs. Design, Setting, and Participants: Population-based matched cohort study using multiple deterministically linked health administrative databases from Ontario, Canada, and including patients testing positive for COVID-19 between January 1, 2020, and December 30, 2021, and followed up until March 31, 2022. Individuals with IMIDs (n = 28 440) who tested positive for COVID-19 were matched with up to 5 individuals without an IMID (n = 126 437) who tested positive for COVID-19. Matching was based on year of birth, sex, neighborhood income, and rural/urban residence. Data analysis was performed from August 6, 2022, to August 21, 2023. Exposure: Diagnosis of an IMID, identified using algorithms based on diagnostic codes, procedures, and specialist visits. Main Outcome and Measure: The main outcome was estimated age- and sex-standardized incidence of VTE. Proportional cause-specific hazard models compared the risk of VTE in people with and without IMIDs. Death was a competing risk. Models adjusted for history of VTE, 2 or more doses of a COVID-19 vaccine 14 or more days prior to COVID-19 diagnosis, and the Charlson Comorbidity Index. Routinely collected health data were used, so the hypothesis tested was formulated after data collection but prior to being granted access to data. Results: The study included 28 440 individuals (16 741 [58.9%] female; 11 699 [41.1%] male) with an IMID diagnosed prior to first COVID-19 diagnosis, with a mean (SD) age of 52.1 (18.8) years at COVID-19 diagnosis. These individuals were matched to 126 437 controls without IMIDs. The incidence of VTE within 6 months of COVID-19 diagnosis among 28 440 individuals with an IMID was 2.64 (95% CI, 2.23-3.10) per 100 000 person-days compared with 2.18 (95% CI, 1.99-2.38) per 100 000 person-days among 126 437 matched individuals without IMIDs. The VTE risk was not statistically significantly different among those with vs without IMIDs (adjusted hazard ratio, 1.12; 95% CI, 0.95-1.32). Conclusions and Relevance: In this retrospective population-based cohort study of individuals with IMIDs following COVID-19, individuals with IMIDs did not have a higher risk of VTE compared with individuals without an IMID. These data provide reassurance to clinicians caring for individuals with IMIDs and COVID-19.

BNIP3 as a potential biomarker for the identification of prognosis and diagnosis in solid tumours.

BACKGROUND: Traditional radiotherapy and chemotherapy have been intensively studied for their role in the treatment of tumours. However, these therapies often cause side effects for patients, which calls for the development of novel treatment options for tumours. B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) reportedly apoptosis-inducing effects in tumour cells and is associated with the progression and treatment of multiple tumours. Nevertheless, little is known about its potential role in tumour diagnosis and targeted therapy. FINDINGS: The results of the study demonstrated that the interaction of BNIP3 with HDAC1 may affect the progression of breast invasive cancer (BRCA), sarcoma (SARC), kidney renal clear cell carcinoma (KIRC), and low-grade glioma (LGG). BNIP3 seemed to exert its effects in BRCA and SARC primarily through gene silencing and integrator complex, and in KIRC and LGG, mainly by affecting olfactory function, suggesting that targeted therapy can be developed based on the above signalling pathway and downstream molecules. INTERPRETATION: BNIP3 has emerged as a promising therapeutic and diagnostic target for BRCA, SARC, KIRC, and LGG, providing new insights into tumour molecular therapies in the clinic.

Primary ovarian choriocarcinoma occurring in a postmenopausal woman: A case report.

BACKGROUND: Nongestational ovarian choriocarcinoma (NGOC) is a rare but aggressive neoplasm with limited sensitivity to chemotherapy and a very poor prognosis. Few cases of NGOC have been reported, and there is limited information regarding its clinical features, treatment protocols, or prognosis. CASE SUMMARY: A postmenopausal woman in her 5th decade of life visited our clinic because of abnormal vaginal bleeding and an abdominal mass. Although she had been menopausal for more than eight years and her last abortion occurred nine years ago, she had an increased level of serum ß-human chorionic gonadotropin (ß-hCG). Thus, an ovarian neoplasm of trophoblastic origin was suspected, and exploratory laparotomy was performed. Based on the patient's clinical history and the histopathological examination and immunohistochemistry results obtained postoperatively, we concluded that she most likely had primary NGOC. Cytoreductive surgery was performed in combination with adjuvant chemotherapy comprising bleomycin, etoposide, and cisplatin. Serum ß-hCG levels decreased to normal after two cycles, and there was no evidence of recurrence after four cycles of chemotherapy. CONCLUSION: Even in postmenopausal women, ovarian choriocarcinoma should be considered in the initial differential diagnosis for an adnexal mass.

WMSA 2: a multiple DNA/RNA sequence alignment tool implemented with accurate progressive mode and a fast win-win mode combining the center star and progressive strategies.

Multiple sequence alignment is widely used for sequence analysis, such as identifying important sites and phylogenetic analysis. Traditional methods, such as progressive alignment, are time-consuming. To address this issue, we introduce StarTree, a novel method to fast construct a guide tree by combining sequence clustering and hierarchical clustering. Furthermore, we develop a new heuristic similar region detection algorithm using the FM-index and apply the k-banded dynamic program to the profile alignment. We also introduce a win-win alignment algorithm that applies the central star strategy within the clusters to fast the alignment process, then uses the progressive strategy to align the central-aligned profiles, guaranteeing the final alignment's accuracy. We present WMSA 2 based on these improvements and compare the speed and accuracy with other popular methods. The results show that the guide tree made by the StarTree clustering method can lead to better accuracy than that of PartTree while consuming less time and memory than that of UPGMA and mBed methods on datasets with thousands of sequences. During the alignment of simulated data sets, WMSA 2 can consume less time and memory while ranking at the top of Q and TC scores. The WMSA 2 is still better at the time, and memory efficiency on the real datasets and ranks at the top on the average sum of pairs score. For the alignment of 1 million SARS-CoV-2 genomes, the win-win mode of WMSA 2 significantly decreased the consumption time than the former version. The source code and data are available at https://github.com/malabz/WMSA2.

Uterine inflammatory myofibroblastic tumor presented as abnormal uterine bleeding: Two cases report and literature review.

RATIONALE: Inflammatory myofibroblastic tumor (IMT) is an extremely rare soft tissue neoplasm consisting of the proliferation of fibroblastic-myofibroblastic cells with inflammatory infiltrates. It is known to occur in many parts of the body and can generally present with benign or locally recurrent behavior. Anaplastic lymphoma kinase is a specific diagnostic marker for IMT, and approximately 50% of IMT patients have anaplastic lymphoma kinase gene rearrangements. Reports of the female genital tract are rare. PATIENT CONCERNS: Two patients (a 32-year-old multigravida and a 22-year-old nullipara) visited our clinic because of abnormal uterine bleeding and a uterine mass. DIAGNOSES: Histopathological examination, immunohistochemical markers, and fluorescence in situ hybridization confirmed the presence of a rare uterine IMT. INTERVENTIONS: The masses were completely resected via hysteroscopy. The multigravida recurred rapidly in terms of symptoms and images, whereas the nullipara was complaint-free during the follow-up period. Finally, the multigravida underwent hysterectomy and bilateral salpingectomies. OUTCOMES AND LESSONS: Uterine IMTs can be easily overlooked because of their extremely low incidence rate and insufficient awareness among clinicians; however, uterine IMTs need to be considered in the differential diagnosis of uterine masses. Possible differences in the biological behavior of IMT may exist in different individuals.

Fabrication of highly fluorinated porphyrin-based covalent organic frameworks decorated Fe3O4 nanospheres for magnetic solid phase extraction of fluoroquinolones.

A highly fluorinated porphyrin-based covalent organic frameworks magnetic adsorbent (FPy-COF@PDA@Fe3O4) was fabricated by using polydopamine (PDA) grafting Fe3O4 nanospheres as magnetic core and FPy-COF as shell for magnetic solid phase extraction (MSPE) of fluoroquinolones (FQs). FPy-COF was constructed by using 5,15-bis(4-aminophenyl)-10,20-bis(perfluorophenyl)porphyrin and 4,4'-biphenyldicarboxaldehyde as two building blocks. PDA as a bridge grafting on the surface of Fe3O4 nanospheres facilitated the growth of FPy-COF. The morphology and structure of FPy-COF@PDA@Fe3O4 adsorbent were characterized in detail. The prepared magnetic adsorbent exhibited good extraction capability to amphiphilic FQs due to their superior chemical affinities such as fluorophilic interaction and hydrogen-bond interaction from nitrogen-rich skeleton. Under the optimized conditions, the MSPE method combined with high performance liquid chromatography with ultraviolet detection (HPLC-UV) was developed to sensitively quantify trace level of six FQs in milk samples. The developed MSPE-HPLC method showed good linearity with wide concentration range, precision, and low limits of detection (S/N = 3) for six FQs as low as 2.3 ngꞏmL-1 in milk. The extraction recoveries of different spiked concentrations were in the range 77.8-110.4% for milk samples with RSD less than 9.7%.

WMSA: a novel method for multiple sequence alignment of DNA sequences.

MOTIVATION: Multiple sequence alignment (MSA) is a fundamental problem in bioinformatics. The quality of alignment will affect downstream analysis. MAFFT has adopted the Fast Fourier Transform method for searching the homologous segments and using them as anchors to divide the sequences, then making alignment only on segments, which can save time and memory without overly reducing the sequence alignment quality. MAFFT becomes slow when the dataset is large. RESULTS: We made a software, WMSA, which uses the divide-and-conquer method to split the sequences into clusters, aligns those clusters into profiles with the center star strategy and then makes a progressive profile-profile alignment. The alignment is conducted by the compiled algorithms of MAFFT, K-Band with multithread parallelism. Our method can balance time, space and quality and performs better than MAFFT in test experiments on highly conserved datasets. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at https://github.com/malabz/WMSA/, which is implemented in C/C++ and supported on Linux, and datasets are available at https://github.com/malabz/WMSA-dataset. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

HAlign 3: Fast Multiple Alignment of Ultra-Large Numbers of Similar DNA/RNA Sequences.

HAlign is a cross-platform program that performs multiple sequence alignments based on the center star strategy. Here we present two major updates of HAlign 3, which helped improve the time efficiency and the alignment quality, and made HAlign 3 a specialized program to process ultra-large numbers of similar DNA/RNA sequences, such as closely related viral or prokaryotic genomes. HAlign 3 can be easily installed via the Anaconda and Java release package on macOS, Linux, Windows subsystem for Linux, and Windows systems, and the source code is available on GitHub (https://github.com/malabz/HAlign-3).

Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad.

Gonadal sex determination represents a unique model for studying cell fate decisions. However, a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. Here, we investigated the origin, specification, and subsequent sex-specific differentiation of a previously uncharacterized population of supporting-like cells (SLCs) in the developing mouse gonads. The SLC lineage is closely related to the coelomic epithelium and specified as early as E10.5, making it the first somatic lineage to be specified in the bipotential gonad. SLC progenitors are localized within the genital ridge at the interface with the mesonephros and initially coexpress Wnt4 and Sox9. SLCs become sexually dimorphic around E12.5, progressively acquire a more Sertoli- or pregranulosa-like identity and contribute to the formation of the rete testis and rete ovarii. Last, we found that WNT4 is a crucial regulator of the SLC lineage and is required for normal development of the rete testis.

Developments in Algorithms for Sequence Alignment: A Review.

The continuous development of sequencing technologies has enabled researchers to obtain large amounts of biological sequence data, and this has resulted in increasing demands for software that can perform sequence alignment fast and accurately. A number of algorithms and tools for sequence alignment have been designed to meet the various needs of biologists. Here, the ideas that prevail in the research of sequence alignment and some quality estimation methods for multiple sequence alignment tools are summarized.

The accurate prediction and characterization of cancerlectin by a combined machine learning and GO analysis.

Cancerlectins, lectins linked to tumor progression, have become the focus of cancer therapy research for their carbohydrate-binding specificity. However, the specific characterization for cancerlectins involved in tumor progression is still unclear. By taking advantage of the g-gap tripeptide and tetrapeptide composition feature descriptors, we increased the accuracy of the classification model of cancerlectin and lectin to 98.54% and 95.38%, respectively. About 36 cancerlectin and 135 lectin features were selected for functional characterization by P/N feature ranking method, which particularly selects the features in positive samples. The specific protein domains of cancerlectins are found to be p-GalNAc-T, crystal and annexin by comparing with lectins through the exclusion method. Moreover, the combined GO analysis showed that the conserved cation binding sites of cancerlectin specific domains are covered by selected feature peptides, suggesting that the capability of cation binding, critical for enzyme activity and stability, could be the key characteristic of cancerlectins in tumor progression. These results will help to identify potential cancerlectin and provide clues for mechanism study of cancerlectin in tumor progression.

Risk factors for post-traumatic stress disorder in acute trauma patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the most commonly reported mental health consequences, followed by disasters and traumatic events, either natural or man-made. At present, there are no unified results for the prevalence rate of PTSD in patients suffering from acute trauma and related influencing factors. Therefore, the purpose of this study is to systematically evaluate the existing literatures, thus obtaining a comprehensive estimation of the combined prevalence rate of PTSD and related factors in trauma patients, so as to provide evidence support for clinical disease prediction models and intervention strategies. METHODS: Published articles will be retrieved from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Research reports will be searched in March 2021. STATA 14.0 software will be applied for data analysis. Mantel-Haenszel fixed effect model or DerSimonian-Laird random effect model will be selected to estimate the pooled prevalence of PTSD in patients with acute trauma and associated factors. RESULTS: We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals. CONCLUSIONS: The results of this analysis can be used to establish a risk prediction model of PTSD in patients experiencing acute trauma, so as to provide intervention strategies. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/Z275U.

Application of Sparse Representation in Bioinformatics.

Inspired by L1-norm minimization methods, such as basis pursuit, compressed sensing, and Lasso feature selection, in recent years, sparse representation shows up as a novel and potent data processing method and displays powerful superiority. Researchers have not only extended the sparse representation of a signal to image presentation, but also applied the sparsity of vectors to that of matrices. Moreover, sparse representation has been applied to pattern recognition with good results. Because of its multiple advantages, such as insensitivity to noise, strong robustness, less sensitivity to selected features, and no "overfitting" phenomenon, the application of sparse representation in bioinformatics should be studied further. This article reviews the development of sparse representation, and explains its applications in bioinformatics, namely the use of low-rank representation matrices to identify and study cancer molecules, low-rank sparse representations to analyze and process gene expression profiles, and an introduction to related cancers and gene expression profile database.

Interaction between DMRT1 and PLZF protein regulates self-renewal and proliferation in male germline stem cells.

Double sex and mab-3 related transcription factor 1 (DMRT1) encodes a double sex/mab-3 (DM) domain, which is the most conserved structure that involved in sex determination both in vertebrates and invertebrates. This study revealed important roles of DMRT1 in maintaining self-renewal of male germline stem cells (mGSCs). Our results showed that insufficient expression of DMRT1 in mice testes resulted in decreased number of spermatogonial cells and collapse of testicular niche in vivo. Self-renewal and proliferation of mGSCs were inhibited. Based on the bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (co-IP) assay, it was finally revealed that the interaction between DMRT1 and promyelocytic leukemia zinc finger (PLZF) protein was essential for maintaining self-renewal of mGSCs. Moreover, BTB domain of PLZF, DM and DMRT1 domain of DMRT1 were indispensable in mGSC, which were responsible for preserving the quantity of germ cells. Our research provided a new scientific basis for studying the mechanism of self-renewal and spermatogenesis in goat mGSCs.

Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9.

The transcription factors SRY and SOX9 and RSPO1/WNT4/ß-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when Sox9 and Wnt4 are both mutated. We show that the XX gonad mutant for Wnt4 or for both Wnt4 and Sox9 develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a Wnt4 mutation. Sox9 deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/ß-catenin signaling. In XY Sox9 mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of Wnt4 or Rspo1, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/ß-Catenin signaling. However, in XY Sox9 Wnt4 double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation.

p53 inhibits the proliferation of male germline stem cells from dairy goat cultured on poly-L-lysine.

Male germline stem cells (mGSCs) can transmit genetic materials to the next generation and dedifferentiate into pluripotent stem cells. However, in livestock, mGSC lines are difficult to establish, because of the factors that affect their isolation and culture. The extracellular matrix serves as a substrate for attachment and affects the fate of these stem cells. Poly-L-lysine (PL), an extracellular matrix of choice, inhibits and/or kills cancer cells, and promotes the attachment of stem cells in culture. However, how it affects the characteristics and potentials of these stem cells in culture needs to be elucidated. Here, we isolated, enriched and cultured dairy goat mGSCs on five types of extracellular matrices. To explore the best extracellular matrix to use for culturing them, the characteristics and proliferation ability of the cells were determined. Results showed that the cells shared several characteristics with previously reported mGSCs, including the poor effect of PL on their proliferative and colony-forming abilities. Further examination showed upregulation of p53 expression in these cells, which could be inhibiting their proliferation. When a p53 inhibitor was included in the culture medium, it was confirmed to be responsible for the inhibition of proliferation in mGSCs. Optimal concentration of the inhibitor in the culture of these cells was 5 µM. Furthermore, addition of the p53 inhibitor increased the expression of the markers of self-renewal and cell cycle in goat mGSCs. In summary, suppressing p53 is beneficial for the proliferation of dairy goat mGSCs, cultured on PL.