Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.

BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.

Incoherent partial superposition modeling for single-shot angle-resolved ellipsometry measurement of thin films on transparent substrates.

Ellipsometric measurement of transparent samples suffers from substrate backside reflection challenges, including incoherent and partial superposition issues. The recently developed angle-resolved ellipsometry (ARE) can naturally eliminate the backside reflections of substrates with a micro-spot equivalent thickness or thicker; however, for thinner substrates, ARE working with general incoherent backside reflection models shows significant inaccuracy or measurement failure. In this paper, an incoherent partial superposition (IPS) model is proposed to characterize the optical superposition effect between the frontside and uncertain backside reflections from an unknown substrate. IPS introduces a cosine-like correction of the backside reflection, corresponding to the overlapping-area change of backside and frontside reflections along with incident angles. Benefiting from ARE's wide-angle spectral imaging capability, IPS achieves single-shot measurement of thin film thicknesses on transparent substrates of unknown thickness. An ARE system was built and calibrated regarding the linear relationship between the cosine-corrected angular frequencies and substrate thicknesses. Then, commercial ITO films on glasses of different thicknesses ranging from 200 to 1000 µm were measured. Experimental results show that IPS-ARE results in a root-mean-square accuracy error of ∼1 nm in film thickness measurement and provides a ∼77% error reduction from general incoherent backside reflection models.

The influence of maternal diet on offspring's gut microbiota in early life.

BACKGROUND: The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. OBJECTIVE: In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved in maternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. CONCLUSION: The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Polarized angle-resolved spectral reflectometry for real-time ultra-thin film measurement.

We propose a polarized, angle-resolved spectral (PARS) reflectometry for simultaneous thickness and refractive-index measurement of ultra-thin films in real time. This technology acquires a two-dimensional, angle-resolved spectrum through a dual-angle analyzer in a single shot by radially filtering the back-focal-plane image of a high-NA objective for dispersion analysis. Thus, film parameters, including thickness and refractive indices, are precisely fitted from the hyper-spectrum in angular and wavelength domains. Through a high-accuracy spectral calibration, a primary PARS system was built. Its accuracy was carefully verified by testing a set of SiO2 thin films of thicknesses within two µm grown on monocrystalline-Si substrates against a commercial spectroscopic ellipsometer. Results show that the single-shot PARS reflectometry results in a root-mean-square absolute accuracy error of ∼1 nm in film thickness measurement without knowing its refractive indices.

All-in-one smart dressing for simultaneous angiogenesis and neural regeneration.

Wound repair, along with skin appendage regeneration, is challenged by insufficient angiogenesis and neural regeneration. Therefore, promoting both proangiogenic and neuro-regenerative therapeutic effects is essential for effective wound repair. However, most therapeutic systems apply these strategies separately or ineffectively. This study investigates the performance of an all-in-one smart dressing (ASD) that integrates angiogenic functional materials and multiple biological factors within a light crosslinked hydrogel, forming a multi-functional dressing capable of facilitating simultaneous micro-vascularization and neural regeneration. The ASD uses a zeolite-imidazolate framework 67 with anchored vanadium oxide (VO2@ZIF-67) that allows for the on-demand release of Co2+ with fluctuations in pH at the wound site to stimulate angiogenesis. It can simultaneously release CXCL12, ligustroflavone, and ginsenoside Rg1 in a sustained manner to enhance the recruitment of endogenous mesenchymal stem cells, inhibit senescence, and induce neural differentiation to achieve in situ nerve regeneration. The ASD can stimulate rapid angiogenesis and nerve regeneration within 17 days through multiple angiogenic and neuro-regenerative cues within one dressing. This study provides a proof-of-concept for integrating functional nanomaterials and multiple complementary drugs within a smart dressing for simultaneous angiogenesis and neural regeneration.

Outer membrane vesicles induce the mussel plantigrade settlement via regulation of c-di-GMP.

Despite the importance of outer membrane vesicles (OMVs) in benthic animal settlement, the underlying molecular mechanism remains elusive. Here, the impact of OMVs and OMVs synthesis-related tolB gene in Mytilus coruscus plantigrade settlement was tested. The OMVs were extracted from Pseudoalteromonas marina through density gradient centrifugation, and a tolB knockout strain, achieved by homologous recombination, was utilized for the investigation. Our results demonstrated that OMVs could significantly enhance M. coruscus plantigrades settlement. Deleting the tolB resulted in downregulation of c-di-GMP, accompanied by a reduction of OMV production, a decline in bacterial motility and increasing biofilm-forming ability. Enzyme treatment resulted in a 61.11% reduction in OMV-inducing activity and a 94.87% reduction in LPS content. Thus, OMVs regulate mussel settlement via LPS, and c-di-GMP is responsible for the OMV-inducing capacity. These findings provide new insights into the interactions between bacteria and mussels.

The effect of implementation of pain neuroscience education and rehabilitation exercise on post-operative pain and recovery after laparoscopic colorectal surgery: a prospective randomized controlled trial.

PURPOSES: To optimize the efficacy of analgesia and post-operative recovery for patients undergoing laparoscopic colorectal surgery by integrating a composite psycho-somatic analgesia algorithm involving peri-operative rehabilitation exercise and pain neuroscience education into multi-modal analgesia. METHODS: A prospective randomized controlled trial was conducted to compare conventional peri-operative analgesia (group CA) and the addition of rehabilitation exercise and pain neuroscience education into it (group REPNE) for patients undergoing laparoscopic colorectal surgery. Acute and chronic post-operative pain, characteristics of pain (pain catastrophizing, sensitization, and trends of neuropathic transformation), and quality of post-operative recovery calibrated with EuroQol Five Dimensions Questionnaire (EQ-5D-5L) were investigated and compared between two groups. RESULTS: A total of 175 patients consented to participate in this study. Compared with those receiving conventional analgesia (group CA, N = 89), patients in group REPNE (N = 86) reported reduced intensity of pain 24 h after surgery, less risk of pain catastrophizing and sensitization, and better quality of life during hospitalization recovery till 1 month after surgery (p < 0.05). No statistical difference was found for neuropathic transformation of post-operative pain or for the incidence of chronic post-operative pain (p > 0.05). CONCLUSIONS: The addition of peri-operative rehabilitation exercise and pain neuroscience education into multi-modal analgesia provided better analgesic effect compared with routine practice for patients receiving laparoscopic colorectal surgery and also facilitated better post-operative recovery. This composite psycho-somatic algorithm for peri-operative analgesia merits further application in clinical practice.

Symptoms compatible with Rome IV functional bowel disorder in patients with ankylosing spondylitis.

OBJECTIVES: To determine the frequency of symptoms meeting Rome IV functional bowel disorder (FBD) in patients with ankylosing spondylitis (AS), investigate factors associated with FBD symptoms, and assess whether having FBD symptoms might influence AS disease activity. METHODS: In this cross-sectional study, we enrolled 153 AS patients without known colonic ulcers and 56 sex- and age-matched controls to evaluate FBD (or its subtypes) symptoms. Disease characteristics were also evaluated in the AS group. RESULTS: Sixty (39.2%) of 153 AS patients had FBD symptoms, which were more prevalent than controls (23.2%). Besides, symptoms compatible with irritable bowel syndrome (IBS) and chronic diarrhoea were detected in 18 and 43 AS patients, respectively. For the AS group, multivariable logistic regression analyses showed that symptoms of FBD, IBS, and chronic diarrhoea were negatively associated with using non-steroidal anti-inflammatory drugs and positively associated with comorbid fibromyalgia, respectively. In exploration about the effects of FBD (or its subtypes) symptoms on AS disease activity by multivariable linear regression analyses, FBD symptoms and chronic diarrhoea had universal positive associations with assessments of AS disease characteristics, respectively. CONCLUSIONS: Patients with AS had frequent symptoms compatible with FBD, IBS, and chronic diarrhoea, proportions of which were lower in those with non-steroidal anti-inflammatory drug use. The improvement of FBD symptoms and chronic diarrhoea might be conducive to the disease status of AS patients.

Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms.

Plant exosome-like nanovesicles, being innately replete with bioactive lipids, proteins, RNA, and other pharmacologically active molecules, offer unique morphological and compositional characteristics as natural nanocarriers. Furthermore, their compelling physicochemical traits underpin their modulative role in physiological processes, all of which have fostered the concept that these nanovesicles may be highly proficient in the development of next-generation biotherapeutic and drug delivery nanoplatforms to meet the ever-stringent demands of current clinical challenges. This review systemically deals with various facets of plant exosome-like nanovesicles ranging from their origin and isolation to identification of morphological composition, biological functions, and cargo-loading mechanisms. Efforts are made to encompass their biotherapeutic roles by elucidating their immunological modulating, anti-tumor, regenerative, and anti-inflammatory roles. We also shed light on re-engineering these nanovesicles into robust, innocuous, and non-immunogenic nanovectors for drug delivery through multiple stringent biological hindrances to various targeted organs such as intestine and brain. Finally, recent advances centered around plant exosome-like nanovesicles along with new insights into transdermal, transmembrane and targeting mechanisms of these vesicles are also elucidated. We expect that the continuing development of plant exosome-like nanovesicle-based therapeutic and delivery nanoplatforms will promote their clinical applications.

Implementation of perioperative breathing exercises and its effect on postoperative pulmonary complications and long-term prognosis in elderly patients undergoing laparoscopic colorectal surgery: A randomized controlled trial.

OBJECTIVE: This study was to investigate the impact of breathing exercises on recovery in elderly patients receiving laparoscopic colorectal surgery. DESIGN: A prospective randomized controlled trial. SETTING: University hospital. SUBJECT: A total of 264 elder patients undergoing laparoscopic colorectal surgery participated in this study. INTERVENTION: Patients in intervention group received respiratory-related exercises based on standardized enhanced recovery after surgery strategies from admission to 90 days after surgery. The control group received perioperative standardized enhanced recovery after surgery strategies without formatted breathing exercises. MAIN MEASURES: The primary outcome was the incidence of postoperative pulmonary complications. The secondary outcomes included 6-minute walking distance, surgery-related complications, length of stay, mortality postoperatively, and hospitalization costs. RESULTS: Completion rate of breathing exercise in intervention group was over 80% till 90 days postoperatively. The incidence of postoperative pulmonary complications was lower in breathing exercises group (17/132 [12.9%] vs. 43/132 [32.6%], p < 0.001). The mean value of 6-minute walking distance increased more in intervention group compared with baseline values preoperatively (44.2 ± 4.3 vs. 3.2 ± 0.2, p < 0.001). On 90 days postoperatively, the mean value of 6-minute walking distance in breathing exercises group increased by 18.8 m compared with its baseline (557.0 ± 133.5 vs. 538.2 ± 112.7, p = 0.022), while that of control group decreased by 53.2 m from baseline (481.9 ± 102.5 vs. 535.1 ± 123.4, p < 0.001). Patients who received breathing exercises had shorter length of stay and lower hospitalization costs (p < 0.050). CONCLUSIONS: Perioperative breathing exercises helped prevent postoperative pulmonary complications and improve long-term prognosis in elderly patients undergoing laparoscopic colorectal surgery.

Plant Exosomes As Novel Nanoplatforms for MicroRNA Transfer Stimulate Neural Differentiation of Stem Cells In Vitro and In Vivo.

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photo-cross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.

Mechanism and Regulation of Microglia Polarization in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, but effective treatments are lacking, and neuroinflammation plays a key role in the pathogenesis. In the innate immune response to cerebral hemorrhage, microglia first appear around the injured tissue and are involved in the inflammatory cascade response. Microglia respond to acute brain injury by being activated and polarized to either a typical M1-like (pro-inflammatory) or an alternative M2-like (anti-inflammatory) phenotype. These two polarization states produce pro-inflammatory or anti-inflammatory. With the discovery of the molecular mechanisms and key signaling molecules related to the polarization of microglia in the brain, some targets that regulate the polarization of microglia to reduce the inflammatory response are considered a treatment for secondary brain tissue after ICH damage effective strategies. Therefore, how to promote the polarization of microglia to the M2 phenotype after ICH has become the focus of attention in recent years. This article reviews the mechanism of action of microglia's M1 and M2 phenotypes in secondary brain injury after ICH. Moreover, it discusses compounds and natural pharmaceutical ingredients that can polarize the M1 to the M2 phenotype.

Fecal Fusobacterium nucleatum harbored virulence gene fadA are associated with ulcerative colitis and clinical outcomes.

OBJECT: Fusobacterium nucleatum (F.nucleatum), a gram-negative, obligately anaerobe of oral commensal，has been regarded as culprit of periodontal diseases previously and is being unveiled as possible pathogen of gastrointestinal disorders. The key virulence factor of F.nucleatum is FadA adhesin for binding and invading of the host's epithelial cells. Here, we detected fecal F.nucleatum and virulence gene fadA in patients with ulcerative colitis(UC) and evaluated the clinical relevance with UC. METHODS AND SUBJECTS: A total of 310 subjects were enrolled including 100 patients with UC, 70 healthy controls (HC), 70 patients with irritable bowel syndrome subtype diarrhea(IBS-D), and 70 colorectal cancer patients(CRC). Stool samples of UC patients compared with healthy controls as well as IBS-D and CRC patients were collected for Polymerase Chain Reaction(PCR) detection of F.nucleatum (based on 16s rRNA) and virulence gene fadA. RESULTS: The detection rate of 16s rRNA based PCR for F.nucleatum of UC patients(39/100, 39.00%) and CRC(26/70, 37.14%) patients are significantly higher than HC (12/70, 17.14%, P < 0.01) and IBS-D patients (14/70, 20.00%, P < 0.01). Moreover, 19 samples were detected fadA positive from 39 F.nucleatum positive samples of UC patients (19/39, 48.72%), which is significantly higher than HC(2/12, 16.66%, P < 0.05). There were 3 samples detected fadA positive from 14 F.nucleatum positive samples of IBS-D patients(3/14, 21.43%) and 13 out of 26(50.00%) of CRC patients, which were both no significant differences compared with UC patients(21.4% vs 48.72%, P > 0.05; 50.00% vs 48.72%, P > 0.05). For both F.nucleatum and fadA gene positive patients, there were no statistical significances between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells(WBC), and hemoglobin compared with negative patients(defined by either F.nucleatum or fadA negative, or both negative). However, it is worth noting that detection rate of F.nucleatum with virulence gene fadA in patients of severe ulcerative colitis was significantly higher than patients with mild and moderate colitis(28.89% vs 10.91%, P < 0.05). In addition, the fecal F.nucleatum and fadA gene positive patients were more likely to have pancolitis other than left-sided colitis(pancolitis/left-sided colitis: 26.92% vs 10.42%, P < 0.05). CONCLUSIONS: The presence of F.nucleatum and fadA gene increased in UC patients, especially in patients with severe colitis and pancolitis. Strains of F.nucleatum harbored virulence gene fadA are suggested to play a role in the pathogenesis of UC.

Depicting the composition of gut microbiota in children with tic disorders: an exploratory study.

BACKGROUND: Symptom improvement in children with tic disorder (TD) following fecal microbiota transplantation led us to investigate the gut microbiota in TD. This exploratory study aims to depict the gut microbial profile in patients with TD and explore the impact of dopamine receptor antagonist (DRA) drugs on the composition and metabolic function of the gut microbiota. METHODS: The gut microbiota were profiled in fecal samples of 49 children with TD and 50 matched healthy controls (HC) using shotgun metagenomic sequencing. A random forest (RF) model was constructed using the gut bacterial species to distinguish TD from HC. Associations between clinical metadata and microbial abundance or function were analyzed using MaAsLin2 and Spearman correlation. RESULTS: The gut microbiota in children with TD was featured by higher abundances of Bacteroides plebeius and Ruminococcus lactaris (a potential pro-inflammatory taxon) and lower abundances of Prevotella stercorea and Streptococcus lutetiensis compared to HC. The constructed RF model accurately distinguished TD from HC based on the gut microbiota profile, resulting in an AUC of 0.884. Significant correlations were observed between tic symptom severity and the abundances of multiple bacterial species and gut microbiota metabolic functions. Multivariate analysis identified an upregulation of 4-aminobutanoate (GABA) degradation in the gut microbiota associated with TD status. The gut microbiota of DRA-treated TD children showed a distinct gut microbiota compared to the treatment-naïve group, represented by an increase in some potential enteric pathogens such as Escherichia coli, a decline in several species including Akkermansia muciniphila, and alterations in various metabolic functions. CONCLUSIONS: Bacterial species promoting inflammatory responses and those modulating neurotransmitters such as GABA may be involved in the pathogenesis of TD. The use of DRA drugs is likely to induce overgrowth of some enteric pathogens and alter the gut microbiota metabolism.

Effect of antibiotic therapy in patients with ulcerative colitis: a meta-analysis of randomized controlled trials.

BACKGROUND: Gut microbiota may play a role in the pathogenesis of ulcerative colitis (UC). Antibiotic therapy for patients with UC has shown conflicting results. OBJECTIVES: To evaluate the effect of antibiotic therapy in treating UC. METHODS: PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure (CNKI) databases were searched to identify randomized controlled trials (RCTs) that evaluated antibiotics compared with placebo or no antibiotics in patients with UC. We extracted and pooled the risk ratio (RR). RESULTS: Twelve RCTs were included in this systematic review and meta-analysis, which included 739 patients with active UC. Antibiotic therapy had statistically significant efficacy in inducing remission rate in patients with UC, observed at the end of trials (random-effect RR = 0.77; 95% confidence interval [CI] 0.60 to 0.98, p = .03) or at 12 months after trials (fixed-effect RR = 0.83; 95% CI 0.73 to 0.94, p = .003). CONCLUSIONS: Antibiotic therapy appeared to induce remission more effectively than a placebo or no antibiotic intervention not only in the short-term but also in the long-term for patients with UC. More high-quality clinical trials are needed before clinical recommendations for antibiotic therapy in UC management are made.

Robust incident angle calibration of angle-resolved ellipsometry for thin film measurement.

Angle-resolved ellipsometry with back focal plane imaging has been found to be of increasing importance in recent industrial sensing by virtue of its rich information provided at various incident and azimuthal angles. To achieve high sensing accuracy, the incident angles of a back focal plane must be accurately calibrated. For this purpose, a simple and robust incident angle calibration method based on full-field Brewster angle fitting is proposed, without expensive tools or complex operations. With this method, a back focal plane image is first captured from boundary reflectance through a high-numerical-aperture objective. By extracting annular data from the image, radius-dependent ellipsometric parameters $ (\psi,{\Delta)}$ are calculated. At the end, the radii of the back focal plane are mapped to the angle of incidence by using a fitted Brewster angle as the reference. The method is validated by simulation and experiments using a homemade angle-resolved ellipsometer and a commercial spectroscopic ellipsometer. The results show that the proposed method provides a 75% error reduction approximately from generally used methods.

[Research progress on role of Chinese medicinal materials and their topical preparations in wound healing by regulating cytokines and growth factors].

Delayed-or non-healing wounds caused by trauma, surgical procedures, acute diseases, or chronic diseases, and proli-ferating scar have a serious impact on patients' quality of life and increase the economic and psychological burden on their families. Therefore, how to accelerate wound healing and obtain satisfactory aesthetic results is of great concern to researchers and is an urgent clinical problem to be solved. In recent years, the mechanisms of Chinese medicinal materials in accelerating wound healing and inhi-biting scar formation by regulating cytokines have been clarified, which provides a scientific basis for revealing the efficacy of Chinese medicinal materials against clinical trauma. This review focuses on the therapeutic effects of active ingredients, extracts, and topical preparations of Chinese medicinal materials through regulating cytokines in the inflammation, proliferation, and remodeling phases of wound healing. It is expected to provide evidence for the application of Chinese medicinal materials in wound therapy.

Performance of copy number variants detection based on whole-genome sequencing by DNBSEQ platforms.

BACKGROUND: DNBSEQ™ platforms are new massively parallel sequencing (MPS) platforms that use DNA nanoball technology. Use of data generated from DNBSEQ™ platforms to detect single nucleotide variants (SNVs) and small insertions and deletions (indels) has proven to be quite effective, while the feasibility of copy number variants (CNVs) detection is unclear. RESULTS: Here, we first benchmarked different CNV detection tools based on Illumina whole-genome sequencing (WGS) data of NA12878 and then assessed these tools in CNV detection based on DNBSEQ™ sequencing data from the same sample. When the same tool was used, the CNVs detected based on DNBSEQ™ and Illumina data were similar in quantity, length and distribution, while great differences existed within results from different tools and even based on data from a single platform. We further estimated the CNV detection power based on available CNV benchmarks of NA12878 and found similar precision and sensitivity between the DNBSEQ™ and Illumina platforms. We also found higher precision of CNVs shorter than 1 kbp based on DNBSEQ™ platforms than those based on Illumina platforms by using Pindel, DELLY and LUMPY. We carefully compared these two available benchmarks and found a large proportion of specific CNVs between them. Thus, we constructed a more complete CNV benchmark of NA12878 containing 3512 CNV regions. CONCLUSIONS: We assessed and benchmarked CNV detections based on WGS with DNBSEQ™ platforms and provide guidelines for future studies.

Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma.

BACKGROUND & AIMS: The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic characterization of multifocal HCC is important for understanding immune escape in different lesions and developing immunotherapy. METHODS: We combined whole-exome/transcriptome sequencing, multiplex immunostaining, immunopeptidomes, T cell receptor (TCR) sequencing and bioinformatic analyses of 47 tumors from 15 patients with HCC and multifocal lesions. RESULTS: IM and MO demonstrated distinct clonal architecture, mutational spectrum and genetic susceptibility. The immune microenvironment also displayed spatiotemporal heterogeneity, such as less T cell and more M2 macrophage infiltration in IM and higher expression of inhibitory immune checkpoints in MO. Similar to mutational profiles, shared neoantigens and TCR repertoires among tumors from the same patients were abundant in IM but scarce in MO. Combining neoantigen prediction and immunopeptidomes identified T cell-specific neoepitopes and achieved a high verification rate in vitro. Immunoediting mainly occurred in MO but not IM, due to the relatively low immune infiltration. Loss of heterozygosity of human leukocyte antigen (HLA) alleles, identified in 17% of multifocal HCC, hampered the ability of major histocompatibility complex to present neoantigens, especially in IM. An integrated analysis of Immunoscore, immunoediting, TCR clonality and HLA loss of heterozygosity in each tumor could stratify patients into 2 groups based on whether they have a high or low risk of recurrence (p = 0.038). CONCLUSION: Our study comprehensively characterized the genetic structure, neoepitope landscape, T cell profile and immunoediting status that collectively shape tumor evolution and could be used to optimize personalized immunotherapies for multifocal HCC. LAY SUMMARY: Immunogenomic features of multifocal hepatocellular carcinoma (HCC) are important for understanding immune-escape mechanisms and developing more effective immunotherapy. Herein, comprehensive immunogenomic characterization showed that diverse genomic structures within multifocal HCC would leave footprints on the immune landscape. Only a few tumors were under the control of immunosurveillance, while others evaded the immune system through multiple mechanisms that led to poor prognosis. Our study revealed heterogeneous immunogenomic landscapes and immune-constrained tumor evolution, the understanding of which could be used to optimize personalized immunotherapies for multifocal HCC.

A bacterial polysaccharide biosynthesis-related gene inversely regulates larval settlement and metamorphosis of Mytilus coruscus.

Larval settlement and metamorphosis is essential for the development of marine invertebrates. Although polysaccharides are involved in larval settlement and metamorphosis of Mytilus coruscus, the molecular basis of polysaccharides underlying this progression remains largely unknown. Here, the roles of the polysaccharide biosynthesis-related gene 01912 of Pseudoalteromonas marina ECSMB14103 in the regulation of larval settlement and metamorphosis were examined by gene-knockout technique. Compared with biofilms (BFs) of the wild-type P. marina, Δ01912 BFs with a higher colanic acid (CA) content showed a higher inducing activity on larval settlement and metamorphosis. Deletion of the 01912 gene caused an increase in c-di-GMP levels, accompanied by a decrease in the motility, an increase in cell aggregation, and overproduction of CA. Thus, the bacterial polysaccharide biosynthesis-related gene 01912 may regulate mussel settlement by producing CA via the coordination of c-di-GMP. This work provides a deeper insight into the molecular mechanism of polysaccharides in modulating mussel settlement.