Subsecond periodic radio oscillations in a microquasar.

Powerful relativistic jets are one of the ubiquitous features of accreting black holes in all scales1-3. GRS 1915 + 105 is a well-known fast-spinning black-hole X-ray binary4 with a relativistic jet, termed a 'microquasar', as indicated by its superluminal motion of radio emission5,6. It has exhibited persistent X-ray activity over the last 30 years, with quasiperiodic oscillations of approximately 1-10 Hz (refs. 7-9) and 34 and 67 Hz in the X-ray band10. These oscillations probably originate in the inner accretion disk, but other origins have been considered11. Radio observations found variable light curves with quasiperiodic flares or oscillations with periods of approximately 20-50 min (refs. 12-14). Here we report two instances of approximately 5-Hz transient periodic oscillation features from the source detected in the 1.05- to 1.45-GHz radio band that occurred in January 2021 and June 2022. Circular polarization was also observed during the oscillation phase.

The evolution of hot Jupiters revealed by the age distribution of their host stars.

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.

Multi-trait analysis of gene-by-environment interactions in large-scale genetic studies.

Identifying genotype-by-environment interaction (GEI) is challenging because the GEI analysis generally has low power. Large-scale consortium-based studies are ultimately needed to achieve adequate power for identifying GEI. We introduce Multi-Trait Analysis of Gene-Environment Interactions (MTAGEI), a powerful, robust, and computationally efficient framework to test gene-environment interactions on multiple traits in large data sets, such as the UK Biobank (UKB). To facilitate the meta-analysis of GEI studies in a consortium, MTAGEI efficiently generates summary statistics of genetic associations for multiple traits under different environmental conditions and integrates the summary statistics for GEI analysis. MTAGEI enhances the power of GEI analysis by aggregating GEI signals across multiple traits and variants that would otherwise be difficult to detect individually. MTAGEI achieves robustness by combining complementary tests under a wide spectrum of genetic architectures. We demonstrate the advantages of MTAGEI over existing single-trait-based GEI tests through extensive simulation studies and the analysis of the whole exome sequencing data from the UKB.

Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

A wide star-black-hole binary system from radial-velocity measurements.

All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.

Identification of two major QTLs for pod shell thickness in peanut (Arachis hypogaea L.) using BSA-seq analysis.

BACKGROUND: Pod shell thickness (PST) is an important agronomic trait of peanut because it affects the ability of shells to resist pest infestations and pathogen attacks, while also influencing the peanut shelling process. However, very few studies have explored the genetic basis of PST. RESULTS: An F2 segregating population derived from a cross between the thick-shelled cultivar Yueyou 18 (YY18) and the thin-shelled cultivar Weihua 8 (WH8) was used to identify the quantitative trait loci (QTLs) for PST. On the basis of a bulked segregant analysis sequencing (BSA-seq), four QTLs were preliminarily mapped to chromosomes 3, 8, 13, and 18. Using the genome resequencing data of YY18 and WH8, 22 kompetitive allele-specific PCR (KASP) markers were designed for the genotyping of the F2 population. Two major QTLs (qPSTA08 and qPSTA18) were identified and finely mapped, with qPSTA08 detected on chromosome 8 (0.69-Mb physical genomic region) and qPSTA18 detected on chromosome 18 (0.15-Mb physical genomic region). Moreover, qPSTA08 and qPSTA18 explained 31.1-32.3% and 16.7-16.8% of the phenotypic variation, respectively. Fifteen genes were detected in the two candidate regions, including three genes with nonsynonymous mutations in the exon region. Two molecular markers (Tif2_A08_31713024 and Tif2_A18_7198124) that were developed for the two major QTL regions effectively distinguished between thick-shelled and thin-shelled materials. Subsequently, the two markers were validated in four F2:3 lines selected. CONCLUSIONS: The QTLs identified and molecular markers developed in this study may lay the foundation for breeding cultivars with a shell thickness suitable for mechanized peanut shelling.

Long-term follow-up of methotrexate and cytarabine in adult patients with Langerhans cell histiocytosis.

The optimal treatment strategy for adult Langerhans cell histiocytosis (LCH) remains unclear. Our previous study demonstrated the remarkable efficacy of combined methotrexate and cytarabine (Ara-C) [MA] therapy in patients newly diagnosed with LCH, with a median follow-up of 2 years. The present article reports long-term follow-up data spanning a median of 78 months (6.5 years) from a single-arm, single-centre, prospective phase 2 clinical trial (NCT02389400) conducted between January 2014 and December 2020. Ninety-five adults with newly diagnosed LCH exhibiting multisystem disease or multifocal single-system involvement underwent MA therapy every 35 days for six cycles. Methotrexate (1 g/m2) was administered by 24 h infusion on day 1 and AraC (0.1 g/m2) by 24 h infusion for 5 days. The primary end-point was event-free survival (EFS). The median patient age was 32 years (range 18-65 years). The overall response rate was 89.5%. Seven patients in this cohort died, and 38 experienced disease reactivation. No degenerative central nervous system diseases were observed. The estimated 6-year overall survival (OS) and EFS rates were 93.2% and 55.2% respectively. Multivariate analysis revealed that risk organ (RO) involvement at baseline (hazard ratio [HR] 6.135 [95% confidence interval (CI) 1.185-32.259]; p = 0.031) and age >40 years at diagnosis (HR 7.299 [95% CI 1.056-21.277]; p = 0.042) were associated with inferior OS. RO (HR 2.604 [95% CI 1.418-4.762]; p = 0.002) and skin (HR 2.232 [95% CI 1.171-4.255]; p = 0.015) involvement at baseline were poor prognostic factors for EFS. Regarding adverse events, four patients developed a second primary malignancy. In conclusion, the MA regimen was a valid and safe therapeutic approach for adult patients newly diagnosed with LCH.

Transcriptome sequencing and expression analysis in peanut reveal the potential mechanism response to Ralstonia solanacearum infection.

BACKGROUND: Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. RESULTS: Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. CONCLUSIONS: This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut.

Enhanced Charge Transfer via S-Scheme Heterojunction Interface Engineering of Supramolecular SubPc-Br/UiO-66 Arrays for Efficient Photocatalytic Oxidation.

Constructing heterojunction of supramolecular arrays self-assembled on metal-organic frameworks (MOFs) with elaborate charge transfer mechanisms is a promising strategy for the photocatalytic oxidation of organic pollutants. Herein, H12 SubPcB-Br (SubPc-Br) and UiO-66 are used to obtain the step-scheme (S-scheme) heterojunction SubPc-Br/UiO-66 for the first time, which is then applied in the photocatalytic oxidation of minocycline. Atomic-level B-O-Zr charge-transfer channels and van der Waals force connections synergistically accelerated the charge transfer at the interface of the SubPc-Br/UiO-66 heterojunction, while the establishment of the B-O-Zr bonds also led to the directional transfer of charge from SubPc-Br to UiO-66. The synergy is the key to improving the photocatalytic activity and stability of SubPc-Br/UiO-66, which is also verified by various characterization methods and theoretical calculations. The minocycline degradation efficiency of supramolecular SubPc-Br/UiO-66 arrays reach 90.9% within 30 min under visible light irradiation. The molecular dynamics simulations indicate that B-O-Zr bonds and van der Waals force contribute significantly to the stability of the SubPc-Br/UiO-66 heterojunction. This work reveals an approach for the rational design of semiconducting MOF-based heterojunctions with improved properties.

Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women.

BACKGROUND: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Unveiling the metabolic and coagulation disruptions in SARS-CoV-2-associated acute macular neuroretinopathy: A case-control study.

SARS-CoV-2 infection has been associated with the increased incidence of acute macular neuroretinopathy (AMN), an infrequent ocular disorder. However, the precise mechanisms underpinning AMN in the context of SARS-CoV-2 infection (AMN-SARS-CoV-2) remain elusive. In this case-control study, 14 patients diagnosed with AMN-SARS-CoV-2 between 2022/12 and 2023/3 were enrolled and compared with 14 SARS-CoV-2-infected individuals without AMN, who served as controls (SARS-CoV-2-no AMN). Metabolomic profiling using ultrahigh-performance liquid chromatography-online electrospray mass spectrometry revealed significant alterations in serum metabolites in AMN-SARS-CoV-2 patients. Coagulation abnormalities were observed in AMN-SARS-CoV-2 patients, and their relationship with metabolic disorders was studied. Finally, a predictive model for AMN-SARS-CoV-2 was established. Seventy-six upregulated and 42 downregulated metabolites were identified in AMN-SARS-CoV-2 cases. Notably, arginine metabolism within the urea cycle was significantly altered, evidenced by variations in ornithine, citrulline,  l-proline, and ADAM levels, correlating with abnormal coagulation markers like platelet crit, fibrinogen degradation product, and fibrinogen. Additionally, increased arginase 1 (AGR1) activity within the urea cycle and reduced nitric oxide synthase activity were observed in AMN-SARS-CoV-2. The integration of urea cycle metabolite levels with coagulation parameters yielded a robust discriminatory model for AMN-SARS-CoV-2, as evidenced by an area under the curve of 0.96. The findings of the present study enhance our comprehension of the underlying metabolic mechanisms associated with AMN-SARS-CoV-2 and offer potential diagnostic markers for this uncommon ocular disorder within the context of SARS-CoV-2 infection.

Co-localization of quantitative trait loci for pod and kernel traits and development of molecular marker for kernel weight on chromosome Arahy05 in peanut (Arachis hypogaea L.).

KEY MESSAGE: Stable QTL for pod and kernel traits were co-localized on chromosome Arahy05, and an INDEL marker at 106,411,957 on Arahy05 was developed and validated to be useful for marker-assisted selection of kernel weight. Pod and kernel traits, such as hundred pod weight (HPW), and hundred kernel weight (HKW), along with pod and kernel sizes, are pivotal determinants of yield in peanut breeding programs. This study sought to identify quantitative trait loci (QTL) that are associated with these pod and kernel traits in peanuts. To achieve this, a recombinant inbred line (RIL) population, was derived from a cross between Yuhua15, a cultivar known for its high yield, and a germplasm accession W1202. The investigation uncovered stable and major QTL that are significantly associated with both pod and kernel weight and were consistently co-localized on chromosomes Arahy05 and Arahy08. Furthermore, an INDEL marker was identified and characterized in the QTL interval on Arahy05. An extensive re-sequencing analysis comprising 395 germplasm accessions led to the discovery of two principal haplotypes within a 500-kb window flanking the aforementioned INDEL marker. The haplotypes exhibited a significant correlation with the HKW in our diverse panel of germplasm accessions. Notably, the 170 accessions harboring the haplotype associated with an increased HKW primarily represented botanical varieties, specifically Arachis hypogaea var. hypogaea and A. hypogaea var. hirsuta. On the other hand, the 137 accessions associated with the alternative haplotype, which corresponded to a reduced HKW, were predominately identified as belonging to botanical varieties within A. hypogaea subsp. fastigiata. The INDEL marker located on Arahy05, which demonstrates close linkage to the pod and kernel traits, would be an efficient approach for marker-assisted selection (MAS) of pod and kernel weight in breeding programs.

Manifestations and outcomes of digestive tract involvement in adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a heterogeneous histiocytosis characterized by proliferation of Langerhans cells. While less common, manifestations of digestive tract involvement in LCH remain largely unrevealed. We conducted a retrospective analysis of demographics, clinical, endoscopic, genetic and follow-up data from 13 adult patients with pathologically confirmed gastrointestinal involvement of LCH (LCH-GI), in a single-center cohort of 465 patients. Digestive tract involvement was observed in 2.80% of LCH patients. At LCH-GI diagnosis, 7 patients (53.8%) had unifocal lesions, and 6 patients (46.2%) had multisystem disease. 6 patients (46.2%) experienced no gastrointestinal symptoms at LCH-GI onset, while others were symptomatic. Stomach was most commonly affected (61.5%), followed by esophagus (23.1%), colon (7.7%) and anus (7.7%). Endoscopic findings varied among 12 patients, including submucosal bulge (8 patients, 66.7%) and non-bulging lesions (4 patients, 33.3%) such as erosions, coarse granular mucosa, and regional abnormal coloration. Among 8 patients with genetic analysis, BRAFV600E mutation was detected in 5 patients (62.5%). The estimated 1-year overall survival rate was 91.7%. Progression-free survival of patients with submucosal bulges under endoscopy was significantly better than those with non-bulging lesions. This study presents 13 cases of LCH with digestive tract involvement. We emphasize the importance of endoscopy and biopsy for pathological examination of lesions such as submucosal bulges and erosions under endoscopy to assist in early detection of LCH. Comprehensive systemic assessment and regular endoscopic monitoring are essential in patient management. Treatment should be individualized with dynamic adjustments during follow-up.

High-Nuclear Co-Added Polyoxometalate-Based Chain: Electrocatalytic Oxygen Production.

A high-nuclear Co-added polyoxometalate (CoAP) was synthesized via a hydrothermal reaction: H14.5K9Na7.5-{[Co8(µ2-OH)(µ3-OH)2(H2O)2(Co(H2O)GeW6O26)(B-α-GeW9O34)2][BO(OH)2][Co12(µ2-OH)(µ3-OH)5(H2O)3(Co(H2O)GeW6O26)(GeW6O26)(B-α-GeW9O34)]}·46H2O (1). The polyoxoanion of 1 contains a large Co20 cluster gathered by lacunary GeW6O26 and GeW9O34 subunits. 1 represents a one-dimensional (1D) chain formed by adjacent polyoxoanions coupling through a CoO6 double bridge, showing the first example of a high-nuclear CoAP-based inorganic chain. 1 served as an efficient electrocatalyst in oxygen evolution reactions (OERs).

The role of myeloid differentiation of hematopoietic stem cells in pregnancy immunological tolerance: a systematic review.

The present research aimed to conduct a comprehensive critical analysis of existing literature, focusing on the differentiation of myeloid cells from hematopoietic stem cells within the context of immunological tolerance during pregnancy. A comprehensive systematic review was conducted by searching databases including PubMed, Scopus Biomedicine, EBSCOhost, ScienceDirect, Embase, Cochrane Library, and Web of Science. The focus was on the role of myeloid differentiation from hematopoietic stem cells in modulating immune tolerance, particularly during pregnancy and in certain disease states where they act to suppress the immune response. The quality of the evidence gathered was assessed using the GRADE rating system. Our analysis maintains objectivity and independence from the outcomes presented. The current systematic review offers a synthesis of existing research on the transformation of hematopoietic stem cells into fibroblasts across different tissue types. A thorough search of databases such as PubMed, EBSCOhost, Embase, ScienceDirect, Cochrane Library, and Web of Science was performed in conjunction with a specialist in medical information to identify original research on the derivation of fibroblasts following hematopoietic stem cell transplantation. This search yielded a total of 159 studies, of which 10 met the criteria for inclusion in this review. Reflecting on the constraints of this preliminary review, further in-depth and scientific investigations are warranted to comprehensively assess the impact of varied treatments, with a recommendation for clinicians to proceed with increased circumspection. The myeloid differentiation pathway of hematopoietic stem cells is pivotal in modulating the immune environment during pregnancy, supporting the sustenance of a healthy gestational period. Future research in this domain is expected to advance our understanding of the immunological processes occurring at the maternal-fetal boundary.

A slow feature analysis approach for the optimization of collective variables.

Molecular dynamics simulations have become increasingly important in understanding the microscopic mechanisms of various molecular systems. However, the high energy barriers in complicated molecules often make it difficult to observe events of interest within a reasonable timescale. To address this issue, researchers have developed a variety of enhanced sampling methods to explore configuration space by adding bias potentials along the slowly changing collective variables (CVs). In this study, we have developed a new tool that combines slow feature analysis and biasing-enhanced sampling methods to identify effective CVs and enhance the sampling efficiency of configuration space. We have demonstrated the effectiveness of this tool through three general examples.

Benefits of osimertinib treat a lung adenocarcinoma patient with germline EGFR T790M, somatic EGFR 19-Del, TP53 and PIK3CA mutations.

BACKGROUND: Somatic mutations in the EGFR gene occur in about 50% of non-small cell lung cancers, with the T790M mutation significantly contributing to secondary resistance against EGFR-TKI drugs. However, EGFR T790M germline mutations rarely occur. CASE PRESENTATION: In this study, we report a case of a lung adenocarcinoma family lineage linked to a germline EGFR T790M mutation. The main subject was diagnosed with stage IV lung adenocarcinoma and experienced a 19-month period without disease progression while treated with Osimertinib. We collected both clinicopathological and familial data from a patient with lung adenocarcinoma. Next-generation sequencing of 40 key genes was performed on the proband's tumor tissue. To detect EGFR germline mutations, Sanger sequencing was conducted on peripheral blood mononuclear cells from the proband and his two daughters. Mutations such as EGFR T790M, EGFR 19-Del, TP53, and PIK3CA were identified in the proband's lung cancer tissue. Additionally, germline EGFR T790M mutations were confirmed in the proband and his daughters through sequencing of their peripheral blood samples. CT scans revealed multiple pulmonary nodules in both daughters. CONCLUSIONS: These observations suggest that germline mutations in EGFR T790M could be strongly linked to a familial predisposition to lung cancer.

Incomplete Histologic Healing and Diminished Biomechanical Strength of Meniscus-Bone Interface After Medial Meniscus Posterior Root Transosseous Repair in a Goat Model.

PURPOSE: To enhance the understanding of histologic healing after repairing medial meniscal posterior root tears (MMPRTs) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling 36 knee joints, were allocated into 3 groups (n = 12): sham group (Sham), root tear group (RT), and root tear with transosseous suture group (RTS). At 12- and 24-week intervals postsurgery, all the knees were harvested for imaging, macroscopic, histologic, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface that connected the tibial and circular fibers of the meniscus with a bony insertion and a root-meniscus transition. A direct fibrous connection was displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs 0.19 ± 0.02, P = .0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = .0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSIONS: The incomplete healing may be attributed to the histologic factors underlying the low healing rate and persistent medial meniscal extrusion. Notably, the region attached to the posterior cruciate ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to enhance the healing of the root-meniscus transition.

Genomic analysis of "Candidatus Liberibacter africanus" strain from Zimbabwe reveals unique virulence and prophage characteristics compared to "Ca. Liberibacter asiaticus".

Citrus Huanglongbing (HLB) is caused by the phloem-limited α-proteobacterium "Candidatus Liberibacter spp.", among which "Ca. Liberibacter africanus" (CLaf) have posed a significant threat to citrus production in Africa near a century. CLaf is closely related to the globally prevalent "Ca. Liberibacter asiaticus" (CLas), whereas little is known about the virulence of CLaf, primarily due to limited genome resources. In this study, we completed the whole-genome assembly and annotation of CLaf strain Zim (from Zimbabwe). Compared to CLas, a total of 102 CLaf unique genes were identified, including 14 potential Sec-dependent effectors (SDEs) genes, 29 phage-associated genes, and 59 genes with hypothetical function. Among 14 SDEs, V9J15_03810 was able to induce a significant hypersensitive response (HR) in Nicotiana benthamiana, indicating its potential as a virulence factor for CLaf. Genome analysis showed that CLaf strain Zim genome harbored a complete prophage region (named P-Zim-1, 42,208 bp). P-Zim-1 retained two immunosuppressive peroxidase genes (V9J15_02125 and V9J15_02130) homologous to CLas prophage SC1/SC2, whereas the lysogen-associated genes encoding integrase (V9J15_01970) and repressor (V9J15_02080) were homologous to the prophage of "Ca. Liberibacter solanacearum", the causal agent of potato zebra chip disease. In addition, P-Zim-1 carried a novel CRISPR/Cas system, including a CRISPR array (located within V9J15_02040, ranging from 443,643 to 443,897) and five CRISPR-related Cas proteins (V9J15_02005, 02010, 02015, 02025 and 02035). This study first characterized the unique genomic feature of CLaf related to virulence and prophage, which will facilitate future research on CLaf biology and African HLB management.