Enhancing organoid culture: harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments.

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM-cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.

Research on the comprehensive child life intervention program (CCLIP) for adjusting medical fear in children with central nervous system (CNS) cancers: a randomized controlled trial study protocol.

BACKGROUND: Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children's quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. METHODS: This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. DISCUSSION: This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Predictive value of platelet-to-albumin ratio combined with the C2HEST score for New-Onset atrial fibrillation in elderly patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common adverse outcome in acute ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI) and is associated with a worse prognosis. The platelet-to-albumin ratio (PAR) has been utilized to predict the severity and prognosis of cardiovascular diseases. This study aims to investigate the predictive value of PAR combined with the C2HEST score for NOAF in the elderly population with STEMI undergoing PCI. METHODS: 445 elderly STEMI patients without a history of atrial fibrillation (AF) who underwent PCI were consecutively enrolled in this study. Multivariate logistic regression analysis was used to identify independent risk factors for NOAF after PCI. RESULTS: 50 patients (11.2%) developed NOAF after PCI. Multivariate logistic regression analysis revealed that heart rate (HR), systemic immune-inflammation index (SII), uric acid (UA), PAR, and C2HEST score were independent risk factors for NOAF. The area under the curve (AUC) of the combined PAR and C2HEST score was 0.839, and Delong's test indicated that the combined model had superior predictive value compared to individual markers (AUC of PAR: 0.738; AUC of C2HEST score: 0.752) (P < 0.05). The addition of PAR and C2HEST score to this model (HR, SII, and UA) significantly improved the reclassification and discrimination ability (IDI 0.175; NRI 0.734, both P < 0.001). During regular follow-up, the incidence of MACE was higher in the NOAF group compared to the non-NOAF group. CONCLUSION: The combination of PAR and the C2HEST score has a high predictive value for NOAF in elderly STEMI patients following PCI.

Long-term outcomes of radiofrequency ablation for intrathoracic goiter up to 5 years: evaluated by computed tomography/magnetic resonance imaging and ultrasound.

OBJECTIVES: This study evaluated the long-term efficacy and safety of radiofrequency ablation (RFA) for intrathoracic goiter (ITG) over a follow-up period exceeding six months. METHODS: From 2017 to 2022, 22 patients (6 males, 16 females) with 24 ITGs treated with RFA at a single medical center were evaluated. All patients underwent ultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI) before RFA. Follow-up CT/MRI was performed six months after the initial RFA and then every 6-12 months. The primary outcomes measured were the degree of extension, goiter volume, volume reduction rate (VRR), tracheal deviation, and tracheal lumen. Additionally, we assessed the outcomes of single-session RFA (n = 16) vs. multiple sessions (n = 8) on goiters and explored the correlation between ITG volume measurements obtained using ultrasonography and CT/MRI. RESULTS: The median follow-up period was 12 months (interquartile range: 6-36.8 months). At the last follow-up, the nodule volume measured by CT/MRI had significantly decreased (76.2 vs. 24.6 mL; p < 0.05), with a VRR of 64.6%. Patients who underwent multiple RFA sessions showed a significantly higher VRR than the single-session patients (63.8 vs. 80.1%, p < 0.05). The intraclass correlation between goiter volumes measured using US and CT/MRI was moderate. CONCLUSION: This study affirms the long-term efficacy and safety of RFA for ITG, providing an alternative treatment for nonsurgical candidates. Multiple RFA sessions may be beneficial for achieving better volume reduction. Sole reliance on ultrasonography is inadequate; therefore, integrating CT/MRI is essential for accurate pre-RFA and follow-up assessments.

Intrathoracic goiters significantly impact both cosmetic appearance and induce numerous compressive symptoms.Radiofrequency ablation brought notable volume reduction and persistent, effective alleviation of compressive symptoms.Radiofrequency ablation presents a promising therapeutic modality with long-term benefits for patients with intrathoracic goiter.

T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis.

Introduction: Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included. Methods: Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively. Results: T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044). Conclusion: T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.

ICU Nurses' Perception of Sensitive Indicators of Quality of Care for ECMO Patients in Guizhou Province, China: A Cross-Sectional Study.

Purpose: This study aimed to investigate the cognitive evaluation level of ICU nurses in Guizhou Province, China, on the sensitivity indicators of nursing quality for ECMO patients. Patients and Methods: This was a cross-sectional observational study conducted in Guizhou Province, China, from May to July 2023, 259 ICU nurses were surveyed. Objective sampling method was used to select the participants from 10 hospitals in Guizhou Province that carried out ECMO. Data were collected through questionnaire survey. Two researchers checked and recorded Epidata 3.1. SPSS 25.0 was used for statistical analysis of the data, and frequency, mean and component ratio were used for descriptive statistical analysis. The importance rating was used to reflect the degree of nurses' agreement with the indicators. Results: The results of this study showed that 79.1% of the 253 ICU nurses in Guizhou Province, China, had not participated in training and courses related to indicators of quality of care evaluation for ECMO patients. The main way for ICU nurses to acquire knowledge related to indicators of quality of care sensitivity for ECMO patients was departmental training, which accounted for 87.4%. And the other ways, in descending order, were public, the matic lectures or academic conferences, journals and magazines; their evaluation scores of the importance of most of the quality of care sensitivity indicators for ECMO patients was moderate, with the scores ranging from 73 to 150. Among them, the range of importance evaluation scores for each indicator was 4.01 ~ 4.48. Conclusion: The overall cognitive evaluation of ICU nurses in Guizhou Province, China, on most sensitivity indicators of quality of care for ECMO patients was moderate, and there is a general lack of systematic courses and training on the knowledge related to ECMO care quality sensitive indicators.

Interferon-induced MXB protein restricts vimentin-dependent viral infection.

Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses. Here, we find that IFN alters the subcellular localization of hundreds of host proteins, and this IFN effect is partially lost upon MXB depletion. The results of our mechanistic study reveal that MXB recognizes vimentin (VIM) and recruits protein kinase B (AKT) to phosphorylate VIM at amino acid S38, which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes, hence causing a restriction of virus infection. These results highlight a new function of MXB in modulating VIM-mediated trafficking, which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.

Extracellular Water Ratio and Phase Angle as Predictors of Exacerbation in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by high-energy metabolism, often leads to malnutrition and is linked to exacerbations. This study investigates the association of malnutrition-related body composition and handgrip strength changes with exacerbation frequencies in COPD patients. METHODS: We analyzed 77 acute exacerbation COPD (AECOPD) patients and 82 stable COPD patients, categorized as frequent and infrequent exacerbators. Assessments included body composition, handgrip strength, nutritional risk, dyspnea scale, and COPD assessment. RESULTS: Among AECOPD patients, there were 22 infrequent and 55 frequent exacerbators. Infrequent exacerbators showed better muscle parameters, extracellular water ratio, phase angle, and handgrip strength. Significant differences in intracellular water, total cellular water, protein, and body cell mass were observed between groups. Logistic regression indicated that extracellular water ratio (OR = 1.086) and phase angle (OR = 0.396) were independently associated with exacerbation risk. Thresholds for exacerbation risk were identified as 0.393 for extracellular water ratio and 4.85° for phase angle. In stable COPD, 13 frequent and 69 infrequent exacerbators were compared, showing no significant differences in weight, muscle, and adipose parameters, but significant differences in extracellular water ratio, phase angle, and handgrip strength. CONCLUSIONS: These findings suggest that increased exacerbations in COPD patients correlate with higher extracellular water ratios and lower phase angles.

Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

Discovery of Ureido-Substituted 4-Phenylthiazole Derivatives as IGF1R Inhibitors with Potent Antiproliferative Properties.

The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating the development of novel agents targeting distinct pathways. To discover potent new anti-HCC compounds, we leveraged scaffold hopping from Sorafenib and introduced morpholine/piperidine moieties to develop ureido-substituted 4-phenylthiazole analogs with optimized physicochemical properties and binding interactions. Notably, compound 27 exhibited potent cytotoxicity against HepG2 cells (IC50 = 0.62 ± 0.34 µM), significantly exceeding Sorafenib (IC50 = 1.62 ± 0.27 µM). Mechanistic investigations revealed that compound 27 potently inhibited HCC cell migration and colony formation, and it induced G2/M arrest and early-stage apoptosis. Kinase profiling revealed IGF1R as a key target, which compound 27 potently inhibited (76.84% at 10 µM). Molecular modeling substantiated compound 27's strong binding to IGF1R via multiple hydrogen bonds. Computational predictions indicate favorable drug-like properties for compound 27. These findings provide a promising drug candidate for the treatment of HCC patients.

Effect of acupuncture intervention time on the therapeutic effect in patients with sudden hearing loss. / é’ˆåˆºä»‹å ¥æ—¶æœºå¯¹çªå‘æ€§è‹æ‚£è€ ç–—æ•ˆçš„å½±å“.

OBJECTIVES: To observe the clinical efficacy of acupuncture intervention at different time for patients with sudden hearing loss. METHODS: According to the timing of acupuncture intervention, 86 patients were divided into early exposure group (n=43) and late exposure group (n=43) . The early exposure group was given acupuncture treatment within 14 days of onset, and the late exposure group was given acupuncture treatment after 14 days of onset. After propensity score matching (PSM, a statistical matching technique for observational data) processing by using SPSS26.0 software, outcomes of 30 cases in the early exposure group and 30 cases in the late exposure group were analyzed. In addition to receiving basic treatment with drugs for vascular dilatation, thrombolysis, nourishing nerve, etc., all patients of the two groups were treated with neck acupuncture ("Neck Seven Meridian Lines" acupuncture), once every other day except Sundays, for a total of 12 time. Before, after the treatment and 3 months after the treatment, the total score of the Tinnitus Handicap Inventory (THI, 0, 2 and 4 points for each of the 25 items, total scores = 100 points) scale was used to evaluate the improvement of tinnitus symptoms caused by hearing loss. The clinical therapeutic effect was evaluated according to the efficacy grading criteria in the Guidelines for Diagnosis and Treatment of Sudden Deafness (2015) and the changes of pure tone audiometry curve. Multivariate Logistic regression was used to analyze the effect of factors that might influence efficacy before propensity score matching. RESULTS: The THI scores of patients in both groups decreased strikingly after the treatment and 3 months' follow-up (P<0.05). Compared with the same time-points of the late exposure group, the total THI scores of post-treatment and 3 months' follow-up were evidently lower in the early exposure group (P<0.05). The effective rate of the early exposure group (22/30, 80.00%) was significantly higher (P<0.05) than that of the late exposure group (16/30, 53.33%). The classification of sudden deafness and the application of traditional Chinese medicine in this study were not independent factors affecting the total effective rate. CONCLUSIONS: The time point of acupuncture intervention is an important factor affecting the effect on hearing and tinnitus disability of patients with sudden deafness. The earlier acupuncture treatment is accepted, the better the therapeutic effect is.

MDM2 accelerated renal senescence via ubiquitination and degradation of HDAC1.

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence. Histone deacetylase (HDAC), a class of histone deacetylases mainly expressed in the nucleus, has emerged as a critical contributor to renal tissues senescence. In this study we investigated the interplay between MDM2 and HDAC1 in renal senescence. We established a natural aging model in mice over a 2-year period that was verified by SA-ß-GAL staining and increased expression of senescence-associated markers such as p21, p16, and TNF-α in the kidneys. Furthermore, we showed that the expression of MDM2 was markedly increased, while HDAC1 expression underwent downregulation during renal senescence. This phenomenon was confirmed in H2O2-stimulated HK2 cells in vitro. Knockout of renal tubular MDM2 alleviated renal senescence in aged mice and in H2O2-stimulated HK2 cells. Moreover, we demonstrated that MDM2 promoted renal senescence by orchestrating the ubiquitination and subsequent degradation of HDAC1. These mechanisms synergistically accelerate the aging process in renal tissues, highlighting the intricate interplay between MDM2 and HDAC1, underpinning the age-related organ function decline.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

Exposure to high concentrations of triphenyl phosphate altered functional performance, liver metabolism and intestinal bacterial composition of aquatic turtles.

Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic effects of residual flame retardants on cultured non-fish species are not concerned commonly. TPhP-induced physiological and biochemical effects in an aquatic turtle were evaluated here by systematically investigating the changes in growth and locomotor performance, hepatic antioxidant ability and metabolite, and intestinal microbiota composition of turtle hatchlings after exposure to different TPhP concentrations. Reduced locomotor ability and antioxidant activity were only observed in the highest concentration group. Several metabolic perturbations that involved in amino acid, energy and nucleotide metabolism, in exposed turtles were revealed by metabolite profiles. No significant among-group difference in intestinal bacterial diversity was observed, but the composition was changed markedly in exposed turtles. Increased relative abundances of some bacterial genera (e.g., Staphylococcus, Vogesella and Lawsonella) probably indicated adverse outcomes of TPhP exposure. Despite having only limited impacts of exposure at environmentally relevant levels, our results revealed potential ecotoxicological risks of residual TPhP for aquatic turtles considering TPhP-induced metabolic perturbations and intestinal bacterial changes.

Genome analysis and classification of Xanthomonas bacteriophage AhaSv, a new member of the genus Salvovirus.

Xanthomonas phage AhaSv was isolated from lake water. Genome sequencing showed that its genome is a linear dsDNA molecule with a length of 55,576 bp and a G+C content of 63.23%. Seventy-one open reading frames (ORFs) were predicted, and no tRNAs were found in the genome. Phylogenetic analysis showed that AhaSv is closely related to members of the genus Salvovirus of the family Casjensviridae. Intergenomic similarity values between phage AhaSv and homologous phages were up to 90.6%, suggesting that phage AhaSv should be considered a member of a new species in the genus Salvovirus.

Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis.

Background: Colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Liver metastasis (LM) is the main cause of death in patients with CRC. Therefore, identification of patients with the greatest risk of liver metastasis is critical for early treatment and reduces the mortality of patients with colorectal cancer liver metastases. Methods: Initially, we characterized cell composition through single-cell transcriptome analysis. Subsequently, we employed copy number variation (CNV) and pseudotime analysis to delineate the cellular origins of LM and identify LM-related epithelial cells (LMECs). The LM-index was constructed using machine learning algorithms to forecast the relative abundance of LMECs, reflecting the risk of LM. Furthermore, we analyzed drug sensitivity and drug targeted gene expression in LMECs and patients with a high risk of LM. Finally, functional experiments were conducted to determine the biological roles of metastasis-related gene in vitro. Results: Single-cell RNA sequencing analysis revealed different immune landscapes between primary CRC and LM tumor. LM originated from chromosomal variants with copy number loss of chr1 and chr6p and copy number gain of chr7 and chr20q. We identified the LMECs cluster and found LM-associated pathways such as Wnt/beta-catenin signaling and KRAS signaling. Subsequently, we identified ten metastasis-associated genes, including SOX4, and established the LM-index, which correlates with poorer prognosis, higher stage, and advanced age. Furthermore, we screened two drugs as potential candidates for treating LM, including Linsitinib_1510, Lapatinib_1558. Immunohistochemistry results demonstrated significantly elevated SOX4 expression in tumor samples compared to normal samples. Finally, in vitro experiments verified that silencing SOX4 significantly inhibited tumor cell migration and invasion. Conclusion: This study reveals the possible cellular origin and driving factors of LM in CRC at the single cell level, and provides a reference for early detection of CRC patients with a high risk of LM.

Fast and accurate variant identification tool for sequencing-based studies.

BACKGROUND: Accurate identification of genetic variants, such as point mutations and insertions/deletions (indels), is crucial for various genetic studies into epidemic tracking, population genetics, and disease diagnosis. Genetic studies into microbiomes often require processing numerous sequencing datasets, necessitating variant identifiers with high speed, accuracy, and robustness. RESULTS: We present QuickVariants, a bioinformatics tool that effectively summarizes variant information from read alignments and identifies variants. When tested on diverse bacterial sequencing data, QuickVariants demonstrates a ninefold higher median speed than bcftools, a widely used variant identifier, with higher accuracy in identifying both point mutations and indels. This accuracy extends to variant identification in virus samples, including SARS-CoV-2, particularly with significantly fewer false negative indels than bcftools. The high accuracy of QuickVariants is further demonstrated by its detection of a greater number of Omicron-specific indels (5 versus 0) and point mutations (61 versus 48-54) than bcftools in sewage metagenomes predominated by Omicron variants. Much of the reduced accuracy of bcftools was attributable to its misinterpretation of indels, often producing false negative indels and false positive point mutations at the same locations. CONCLUSIONS: We introduce QuickVariants, a fast, accurate, and robust bioinformatics tool designed for identifying genetic variants for microbial studies. QuickVariants is available at https://github.com/caozhichongchong/QuickVariants .

Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.

Characteristics and whole-genome analysis of a novel Pseudomonas syringae pv. tomato bacteriophage D6 isolated from a karst cave.

Pseudomonas syringae is a gram-negative plant pathogen that infects plants such as tomato and poses a threat to global crop production. In this study, a novel lytic phage infecting P. syringae pv. tomato DC3000, named phage D6, was isolated and characterized from sediments in a karst cave. The latent period of phage D6 was found to be 60 min, with a burst size of 16 plaque-forming units per cell. Phage D6 was stable at temperatures between 4 and 40 °C but lost infectivity when heated to 70 °C. Its infectivity was unaffected at pH 6-10 but became inactivated at pH ≤ 5 or ≥ 12. The genome of phage D6 is a linear double-stranded DNA of 307,402 bp with a G + C content of 48.43%. There is a codon preference between phage D6 and its host, and the translation of phage D6 gene may not be entirely dependent on the tRNA library provided by the host. A total of 410 open reading frames (ORFs) and 14 tRNAs were predicted in its genome, with 92 ORFs encoding proteins with predicted functions. Phage D6 showed low genomic similarity to known phage genomes in the GenBank and Viral sequence databases. Genomic and phylogenetic analyses revealed that phage D6 is a novel phage. The tomato plants were first injected with phage D6, and subsequently with Pst DC3000, using the foliar spraying and root drenching inoculum approach. Results obtained after 14 days indicated that phage D6 inoculation decreased P. syringae-induced symptoms in tomato leaves and inhibited the pathogen's growth in the leaves. The amount of Pst DC3000 was reduced by 150- and 263-fold, respectively. In conclusion, the lytic phage D6 identified in this study belongs to a novel phage within the Caudoviricetes class and has potential for use in biological control of plant diseases.