Nerve growth factor gene polymorphisms may be associated with heroin dependence in women but do not mediate specific personality traits.

Heroin dependence (HD) is a complex disease with a substantial genetic contribution and is associated with traits of impulsivity and specific personality traits. The neurotrophic factor nerve growth factor (NGF) may mediate the reward processes in HD. This study aims to investigate whether NGF gene polymorphisms are associated with the co-occurrence of HD and impulsivity/specific personality traits in HD patients. To minimize the potential confounding effects of population stratification, we selected a homogeneous Han Chinese population and recruited 1364 participants (831 HD patients and 533 healthy controls). In addition, 163 female HD patients completed the Chinese version of the Barratt Impulsiveness Scale Version 11 (BIS-11), and 440 HD patients completed the Chinese version of the Tridimensional Personality Questionnaire (TPQ) for subsequent analysis. We identified three polymorphisms with altered allele and genotype frequency in HD patients versus controls (p = 0.035 for rs2254527; p = 0.005 for rs6678788; p = 0.006 for rs7523654), especially in the female subgroup. Four associations identified via haplotype analysis were significant in the female subgroup (p = 0.003 for T-T-A haplotype and p = 0.002 for C-C-A haplotype in block 1; p = 0.011 for T-T haplotype and p = 0.009 for C-T haplotypes in block 2), but not in the male subgroup. Male HD patients had higher novelty-seeking (NS) scores, and female HD patients had higher harm avoidance (HA) scores. However, there was no significant association between the selected NGF polymorphisms and BIS or TPQ scores in HD patients. NGF variants may contribute to the risk of HD development in females but do not mediate the relationship between impulsivity and specific personality traits in the female population.

Two families with spondylo-epi-metaphyseal dysplasia due to compound heterozygocity in the vWFA domain of MATN3.

Heterozygous variants of MATN3 is one of the common causes of multiple epiphyseal dysplasia (MED). Here we report three individuals from two unrelated families who harbor compound heterozygous variants in MATN3 (p.Arg121Trp and p.Val220Ala). Contrary to the MED phenotype, these individuals exhibit spondyloepimetaphyseal dysplasia (SEMD) resembling the phenotypes caused by homozygous MATN3 variants. Clinical manifestations included short stature, aggravating genu varum, joint laxity, and spinal abnormalities. Radiographic findings were distinct from typical MED. These compound heterozygous variants in the von Willebrand factor A domain of MATN3 expand the phenotypic spectrum associated with MATN3, and suggest that extreme MATN3 dysfunction resulting from dual variants can lead to a specific pattern of SEMD.

May-Thurner Syndrome and Malignancy-Associated Deep Venous Thrombosis: A Case of Successful Treatment with Endovascular Therapy.

In May-Thurner syndrome (MTS), the left iliac vein is compressed by the right iliac artery, leading to restricted blood flow from the leg to the heart. MTS commonly manifests in young females; however, its occurrence in older adults necessitates verifying the possibility of malignancy. A 77-year-old female experienced leg swelling and discomfort for 1 week. Computed tomography angiography suggested extensive thrombosis in the left iliac vein. Despite heparin treatment, the thrombus persisted and required mechanical thrombectomy, balloon venoplasty, and stent placement for tight iliac vein stenosis. The procedure was successful; however a biopsy of thrombus revealed malignant cells. An underlying malignancy and a hypercoagulable state were identified as the contributing factors after further evaluations. This case underscores the importance for vigilant diagnosis of hypercoagulable conditions and malignancies in MTS, emphasizing the role of malignancy in the development of DVT and MTS.

Identification of senescent cell subpopulations by CITE-seq analysis.

Cellular senescence, a state of persistent growth arrest, is closely associated with aging and age-related diseases. Deciphering the heterogeneity within senescent cell populations and identifying therapeutic targets are paramount for mitigating senescence-associated pathologies. In this study, proteins on the surface of cells rendered senescent by replicative exhaustion and by exposure to ionizing radiation (IR) were identified using mass spectrometry analysis, and a subset of them was further studied using single-cell CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) analysis. Based on the presence of proteins on the cell surface, we identified two distinct IR-induced senescent cell populations: one characterized by high levels of CD109 and CD112 (cluster 3), the other characterized by high levels of CD112, CD26, CD73, HLA-ABC, CD54, CD49A, and CD44 (cluster 0). We further found that cluster 0 represented proliferating and senescent cells in the G1 phase of the division cycle, and CITE-seq detection of cell surface proteins selectively discerned those in the senescence group. Our study highlights the heterogeneity of senescent cells and underscores the value of cell surface proteins as tools for distinguishing senescent cell programs and subclasses, paving the way for targeted therapeutic strategies in disorders exacerbated by senescence.

Evaluation of Tibial Slope on Radiographs in Pediatric Patients With Tibial Spine Fractures: An Age- and Sex-Matched Study.

Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.

FUS-Mediated Inhibition of Myogenesis Elicited by Suppressing TNNT1 Production.

Myogenesis is a highly orchestrated process whereby muscle precursor cells, myoblasts, develop into muscle fibers to form skeletal muscle during embryogenesis and regenerate adult muscle. Here, we studied the RNA-binding protein FUS (fused in sarcoma), which has been implicated in muscular and neuromuscular pathologies but is poorly characterized in myogenesis. Given that FUS levels declined in human and mouse models of skeletal myogenesis, and that silencing FUS enhanced myogenesis, we hypothesized that FUS might be a repressor of myogenic differentiation. Interestingly, overexpression of FUS delayed myogenesis, accompanied by slower production of muscle differentiation markers. To identify the mechanisms through which FUS inhibits myogenesis, we uncovered RNA targets of FUS by ribonucleoprotein immunoprecipitation (RIP) followed by RNA-sequencing (RNA-seq) analysis. Stringent selection of the bound transcripts uncovered Tnnt1 mRNA, encoding troponin T1 (TNNT1), as a major effector of FUS influence on myogenesis. We found that in myoblasts, FUS retained Tnnt1 mRNA in the nucleus, preventing TNNT1 expression; however, reduction of FUS during myogenesis or by silencing FUS released Tnnt1 mRNA for export to the cytoplasm, enabling TNNT1 translation and promoting myogenesis. We propose that FUS inhibits myogenesis by suppressing TNNT1 expression through a mechanism of nuclear Tnnt1 mRNA retention.

Effect of a Combination of Lactiplantibacillus plantarum KC3 and Leonurus japonicus Extracts in Respiratory Discomfort: A Randomized, Double-Blind, Placebo-Controlled Trial.

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.

Typical Development of the Secondary Ossification Centers of the Acetabulum and Their Effects on Acetabular Coverage of the Femoral Head.

BACKGROUND: We investigated the normal development of the secondary ossification centers of the acetabulum, focusing on their location and the amount of acetabular coverage increased by them. METHODS: We enrolled 132 patients who were 7 to 16 years of age and had no pelvic deformity but did have ≥1 os ischium, os ilium, and/or os pubis on abdominal or pelvic computed tomographic (CT) scans. The locations of the ossification centers were evaluated by adopting an orientation using 0° for the superior acetabulum, 90° for the anterior acetabulum, 180° for the inferior acetabulum, and 270° for the posterior acetabulum, on a reconstructed 3-dimensional (3D) CT image. The acetabular coverage increase by the os ischium, os ilium, or os pubis was defined as the difference in the posterior acetabular sector angle (ΔPASA), posterosuperior acetabular sector angle (ΔPSASA), superior acetabular sector angle (ΔSASA), anterosuperior acetabular sector angle (ΔASASA), or anterior acetabular sector angle (ΔAASA) measured with and without each secondary ossification center. Patients were grouped into 3 age ranges: late childhood, preadolescence, and early adolescence. The location of each ossification center and the increase in acetabular coverage were compared between these groups. RESULTS: In the late-childhood group, the median start-to-end positions in right hips were 269° to 316° for the os ischium, 345° to 356° for the os ilium, and 81° to 99° for the os pubis. These positions tended to be wider in the early-adolescence group at 252° to 328° for the os ischium (p < 0.001), 338° to 39° for the os ilium (p = 0.005), and 73° to 107° for the os pubis (p = 0.049) in right hips. In right hips in the late-childhood group, the median values were 8.1° for ΔPASA, 14.0° for ΔPSASA, 9.9° for ΔSASA, 11.1° for ΔASASA, and 3.9° for ΔAASA; and in the early-adolescence group, the median values in right hips were 10.7° for ΔPASA, 12.9° for ΔPSASA, 8.4° for ΔSASA, 7.4° for ΔASASA, and 5.6° for ΔAASA. Only the median ΔPASA was larger in the early-adolescence group than in the late-childhood group (p = 0.026). Similar results were observed in left hips. CONCLUSIONS: In early adolescence, the secondary ossification centers appeared at more extended areas along the acetabular rim, and the increase in acetabular coverage by the secondary ossification centers tended to be larger in the posterior area but not in the anterior or superior area. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Incidence and Characteristics of Pelvic-Origin Varicosities in Patients with Complex Varices Evaluated by Ultrasonography.

OBJECTIVE: The purpose of this study was to evaluate the incidence of gonadal vein refluxes associated with lower-extremity varicose veins with Doppler ultrasonography (DUS). METHOD: A total of 6279 patients with venous disease-related symptoms of the lower extremity were evaluated with DUS in the vascular lab. Gonadal vein reflux using abdominal ultrasound was further evaluated in patients with unusual varices, defined as varices in the inguinal, inner or upper thigh and the vulvar area without refluxes in the saphenofemoral junction (SPJ). Those patients who showed gonadal vein reflux were diagnosed as having pelvic-origin varicosity. RESULTS: Unusual varices were found in a total of 237 patients (3.8%), and of these patients, pelvic-origin varicosity was discovered with transabdominal ultrasound in 156 (65.8%). A total of 66.7% (n = 38/57) of unusual varix patients with pelvic pain had gonadal vein reflux. The measurement of gonadal vein diameter was larger in ultrasonography than CT scans (8.835 vs. 8.81, p < 0.001). Two patients with severe symptoms but no obstructive venous diseases were treated with gonadal vein embolization. CONCLUSION: The incidence of pelvic-origin varicosities was 2.5% (n = 156/6279). However, more than half of the patients with unusual varices had gonadal vein reflux and 24.4% of these patients also presented with pelvic pain. The evaluation of pelvic-origin varicosities should be performed in patients who present with unusual forms of varices of the lower extremity.

Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent cell survival.

RNA modifications, including N6-methyladenosine (m6A), critically modulate protein expression programs in a range of cellular processes. Although the transcriptomes of cells undergoing senescence are strongly regulated, the landscape and impact of m6A modifications during senescence are poorly understood. Here, we report a robust m6A modification of PTCHD4 mRNA, encoding Patched Domain-Containing Protein 4, in senescent cells. The METTL3/METTL14 complex was found to incorporate the m6A modification on PTCHD4 mRNA; addition of m6A rendered PTCHD4 mRNA more stable and increased PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as responsible for the stabilization and increased abundance of m6A-modified PTCHD4 mRNA. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells and sensitized them to senolysis and apoptosis. Our results indicate that m6A modification of PTCHD4 mRNA increases the production of PTCHD4, a protein associated with senescent cell survival, supporting the notion that regulating m6A modification on specific mRNAs could be exploited to eliminate senescent cells for therapeutic benefit.

Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited ANKRD1 mRNA Stabilization.

Cellular senescence is a dynamic biological process triggered by sublethal cell damage and driven by specific changes in gene expression programs. We recently identified ANKRD1 (ankyrin repeat domain 1) as a protein strongly elevated after triggering senescence in fibroblasts. Here, we set out to investigate the mechanisms driving the elevated production of ANKRD1 in the early stages of senescence. Our results indicated that the rise in ANKRD1 levels after triggering senescence using etoposide (Eto) was the result of moderate increases in transcription and translation, and robust mRNA stabilization. Antisense oligomer (ASO) pulldown followed by mass spectrometry revealed a specific interaction of the RNA-binding protein RBMS1 with ANKRD1 mRNA that was confirmed by ribonucleoprotein immunoprecipitation analysis. RBMS1 abundance decreased in the nucleus and increased in the cytoplasm during Eto-induced senescence; in agreement with the hypothesis that RBMS1 may participate in post-transcriptional stabilization of ANKRD1 mRNA, silencing RBMS1 reduced, while overexpressing RBMS1 enhanced ANKRD1 mRNA half-life after Eto treatment. A segment proximal to the ANKRD1 coding region was identified as binding RBMS1 and conferring RBMS1-dependent increased expression of a heterologous reporter. We propose that RBMS1 increases expression of ANKRD1 during the early stages of senescence by stabilizing ANKRD1 mRNA.

UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice.

UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure.

Retinoic acid modulation of granule cell activity and spatial discrimination in the adult hippocampus.

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARß) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

Characteristics of terminal hemimelia: What is the difference between terminal hemimelia and classic fibular hemimelia?

Purpose: Fibular hemimelia has denoted a spectrum of postaxial longitudinal deficiency with fibular aplasia/hypoplasia; the term "terminal hemimelia" is reserved for patients with postaxial longitudinal deficiency having a normal fibula. We aimed to delineate the characteristics of terminal hemimelia. Methods: In total, 30 patients with postaxial longitudinal deficiency who had a normal or hypoplastic fibula and visited our institution between 1992 and 2022 were reviewed. Patients were divided into terminal hemimelia and classic fibular hemimelia groups, and their demographic characteristics and clinical and radiographic findings were compared. Results: Femoral shortening, knee valgus, and tibial spine hypoplasia were less common in terminal hemimelia (n = 13) than in classic fibular hemimelia (n = 17) (p = 0.03, p < 0.001, and p = 0.003, respectively). None of the patients in the terminal hemimelia group exhibited knee instability, whereas 12% of patients with classic fibular hemimelia did. Ball-and-socket ankle and absence of lateral rays were commonly observed in both groups. However, tarsal coalition was observed less frequently in terminal hemimelia (p = 0.004). All terminal hemimelia patients exhibited a painless plantigrade foot without ankle instability. Despite limb-length discrepancy at maturity averaging 40.4 mm for terminal hemimelia and 67.0 mm for classic fibular hemimelia (p < 0.001), patients with terminal hemimelia, except for one, exhibited > 20 mm of limb-length discrepancy. However, 46% of them underwent limb-length equalization procedures, mostly single-stage tibial lengthening, at a mean age of 11.2 years. Conclusion: Terminal hemimelia may present with a milder phenotype than classic fibular hemimelia. It mainly overlaps with the symptoms of fibular hemimelia below the ankle joint and manifests as limb-length discrepancy. However, a considerable number of patients with terminal hemimelia required limb-length equalization procedures, for example single-stage tibial lengthening. Level of evidence: level IV.

B. longum CKD1 enhances the efficacy of anti-diabetic medicines through upregulation of IL- 22 response in type 2 diabetic mice.

The gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of combining the effects of Bifidobacterium longum NBM7-1 (CKD1) with anti-diabetic medicines, LobeglitazoneⓇ (LO), SitagliptinⓇ (SI), and MetforminⓇ (Met), to alleviate hyperglycemia in a diabetic mouse model. CKD1 effectively mitigated insulin resistance, hepatic steatosis, and enhanced pancreatic ß-cell function, as well as fortifying gut-tight junction integrity. In the same way, SI-CKD1 and Met- CKD1 synergistically improved insulin sensitivity and prevented hepatic steatosis, as evidenced by the modulation of key genes associated with insulin signaling, ß-oxidation, gluconeogenesis, adipogenesis, and inflammation by qRT-PCR. The comprehensive impact on modulating gut microbiota composition was observed, particularly when combined with MetforminⓇ. This combination induced an increase in the abundance of Rikenellaceae and Alistipes related negatively to the T2DM incidence while reducing the causative species of Cryptosporangium, Staphylococcaceae, and Muribaculaceae. These alterations intervene in gut microbiota metabolites to modulate the level of butyrate, indole-3-acetic acid, propionate, and inflammatory cytokines and to activate the IL-22 pathway. However, it is meaningful that the combination of B. longum NBM7-1(CKD1) reduced the medicines' dose to the level of the maximal inhibitory concentrations (IC50). This study advances our understanding of the intricate relationship between gut microbiota and metabolic disorders. We expect this study to contribute to developing a prospective therapeutic strategy modulating the gut microbiota.

p-Phenylenediamine-Bridged Binder-Electrolyte-Unified Supramolecules for Versatile Lithium Secondary Batteries.

The binder is an essential component in determining the structural integrity and ionic conductivity of Li-ion battery electrodes. However, conventional binders are not sufficiently conductive and durable to be used with solid-state electrolytes. In this study, a novel system is proposed for a Li secondary battery that combines the electrolyte and binder into a unified structure, which is achieved by employing para-phenylenediamine (pPD) moiety to create supramolecular bridges between the parent binders. Due to a partial crosslinking effect and charge-transferring structure of pPD, the proposed strategy improves both the ionic conductivity and mechanical properties by a factor of 6.4 (achieving a conductivity of 3.73 × 10-4 S cm-1 for poly(ethylene oxide)-pPD) and 4.4 (reaching a mechanical strength of 151.4 kPa for poly(acrylic acid)-pPD) compared to those of conventional parent binders. As a result, when the supramolecules of pPD are used as a binder in a pouch cell with a lean electrolyte loading of 2 µL mAh-1 , a capacity retention of 80.2% is achieved even after 300 cycles. Furthermore, when it is utilized as a solid-state electrolyte, an average Coulombic efficiency of 99.7% and capacity retention of 98.7% are attained under operations at 50 °C without external pressure or a pre-aging process.

Incidence and Clinical Characteristics of Slipped Capital Femoral Epiphysis in Patients with Endocrinopathy: A Population-Based Cohort Study.

BACKGROUND: Endocrinopathy is a risk factor for slipped capital femoral epiphysis (SCFE). We aimed to determine (1) the incidence of endocrinopathy-associated SCFE compared with that of non-endocrinopathy-associated SCFE, (2) whether the incidence of SCFE increases with the number of deficient hormones, and (3) the clinical characteristics of endocrinopathy-associated SCFE. METHODS: We conducted a population-based cohort study using a nationwide database in South Korea. All new diagnoses of endocrinopathy or SCFE between 2002 and 2019 in children born between 2002 and 2005 were identified. The incidence of SCFE was calculated for each type of endocrinopathy. The trend of the incidence of SCFE relative to the number of deficient hormones was analyzed. The male:female ratio was compared between endocrinopathy-associated SCFE and non-endocrinopathy-associated SCFE. For endocrinopathy-associated SCFE, the time between the diagnoses of SCFE and endocrinopathy was evaluated. RESULTS: The incidence of SCFE was higher in children with endocrinopathy than in those without endocrinopathy (37.1/100,000 versus 9.0/100,000 children) (relative risk, 4.1 [95% confidence interval, 2.8-6.1]). Among various endocrinopathies, growth hormone deficiency showed the highest incidence of SCFE (583.8/100,000 children). The Cochran-Armitage test showed a linear trend, with an increased number of deficient hormones being associated with a higher incidence of SCFE (p < 0.001). Male sex was dominant in the non-endocrinopathy-associated SCFE group (73%; 117 of 161), whereas female sex was dominant in the endocrinopathy-associated SCFE group (53%; 16 of 30) (p = 0.009). Twenty-two of the 30 cases of endocrinopathy-associated SCFE were diagnosed after the diagnosis of endocrinopathy, with a median time of 3.6 years between the diagnoses. Six (27%) of these 22 children developed SCFE >5 years after the diagnosis of endocrinopathy. CONCLUSIONS: The incidence of SCFE was approximately 4 times higher in children with endocrinopathy than in those without endocrinopathy. The risk of SCFE increased with an increased number of deficient hormones. Long-term monitoring of SCFE occurrence in children with endocrinopathies is strongly recommended. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

Transcriptome profiles of Streptomyces clavuligerus strains producing different titers of clavulanic acid.

Streptomyces clavuligerus NRRL 3585 is a native producer of clavulanic acid (CA), a clinically used ß-lactamase inhibitor, and is widely used as an industrial strain for the production of antibiotics. Selective random mutagenesis has successfully generated the improved CA-producing S. clavuligerus mutant strains as well as the strain with the loss of CA biosynthesis. To understand the molecular mechanisms associated with the improved CA-production potential, genome-scale RNA-sequencing-based transcriptional data were obtained for the wild-type S. clavuligerus strain and its three mutant strains. Total RNA samples for each strain were collected across four different growth stages, and all 32 sequencing data points exhibited an average Phred score of 36. The high-quality genome-scale transcriptional profile of S. clavuligerus strains with varied CA biosynthetic potential provides valuable insights and new opportunities for discovering efficient metabolic engineering strategies for the development of improved industrial strains.