Parameter identifiability of a within-host SARS-CoV-2 epidemic model.

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

Characterization of phospholipidome in milk, yogurt and cream, and phospholipid differences related to various dairy processing methods.

Milk phospholipids have multiple health benefits, but the deficiency of detailed phospholipid profiles in dairy products brings obstacles to intake calculation and function evaluation of dairy phospholipids. In present study, 306 phospholipid molecular species were identified and quantified among 207 milk, yogurt and cream products using a HILIC-ESI-Q-TOF MS and a HILIC-ESI-QQQ MS. The phospholipid profiles of five mammals' milk show that camel milk contains the most abundant phosphatidylethanolamine, phosphatidylserine and sphingomyelin; cow, yak and goat milk have similar phospholipidomes, while buffalo milk contains abundant phosphatidylinositol. Fewer plasmalogens but more lyso-glycerolphospholipids were found in ultra-high-temperature (UHT) sterilized milk than in pasteurized milk, and higher proportions of lyso-glycerolphospholipid/total phospholipid were observed in both cream and skimmed/semi-skimmed milk than whole milk, indicating that UHT and skimming processes improve glycerolphospholipid degradation and phospholipid nutrition loss. Meanwhile, more diacyl-glycerolphospholipids and less of their degradation products make yogurt a better phospholipid resource than whole milk.

Microbiota profiling reveals alteration of gut microbial neurotransmitters in a mouse model of autism-associated 16p11.2 microduplication.

The gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/ß-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.

The gut metabolite indole-3-propionic acid activates ERK1 to restore social function and hippocampal inhibitory synaptic transmission in a 16p11.2 microdeletion mouse model.

BACKGROUND: Microdeletion of the human chromosomal region 16p11.2 (16p11.2 + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 + / -  syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 + / -  are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 + / - , as well as the underlying molecular mechanisms. RESULTS: Mice with the 16p11.2 + / -  showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. CONCLUSIONS: Our study reveals that 16p11.2 + / -  leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 + / -  mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract.

A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

mEnrich-seq: methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome.

Metagenomics has enabled the comprehensive study of microbiomes. However, many applications would benefit from a method that sequences specific bacterial taxa of interest, but not most background taxa. We developed mEnrich-seq (in which 'm' stands for methylation and seq for sequencing) for enriching taxa of interest from metagenomic DNA before sequencing. The core idea is to exploit the self versus nonself differentiation by natural bacterial DNA methylation and rationally choose methylation-sensitive restriction enzymes, individually or in combination, to deplete host and background taxa while enriching targeted taxa. This idea is integrated with library preparation procedures and applied in several applications to enrich (up to 117-fold) pathogenic or beneficial bacteria from human urine and fecal samples, including species that are hard to culture or of low abundance. We assessed 4,601 bacterial strains with mapped methylomes so far and showed broad applicability of mEnrich-seq. mEnrich-seq provides microbiome researchers with a versatile and cost-effective approach for selective sequencing of diverse taxa of interest.

Predictive value of magnetic resonance imaging indications of spinal cord swelling for cervical spondylotic myelopathy prognosis.

BACKGROUND: Magnetic resonance imaging (MRI) is the preferred examination approach for patients with suspected cervical spondylotic myelopathy (CSM). OBJECTIVE: To investigate the predictive value of MRI spinal cord swelling on the prognosis of decompression surgery in patients with CSM. METHODS: A retrospective analysis of 115 patients with CSM who underwent decompression surgery was performed. According to whether cervical MRI showed spinal cord swelling, they were divided into a spinal cord swelling group and non-swelling group. The Modified Japanese Orthopaedic Association (MJOA) score, MJOA improvement rate and abnormal spinal cord enhancement rate in the two groups were compared before and after surgery. Multiple linear regression was used to analyse the influencing factors of the MJOA improvement rate. RESULTS: The time from symptom onset to operation (t= 2.400, p= 0.018) and preoperative MJOA score in the spinal cord swelling group were lower than those in the non-swelling group (t= 3.253, p= 0.002). The body mass index (t= 2.895, p= 0.005), anteroposterior diameter of the spinal canal (t= 4.421, p< 0.001), cross-sectional area (t= 3.136, p= 0.002), postoperative improvement rate (t= 4.277, p< 0.001) and proportion of abnormal enhancement of the spinal cord in the swelling group were higher than those in the non-swelling group (χ2= 3.136, p= 0.002). The preoperative MJOA score in the swelling group was lower than that in the non-swelling group (t= 2.583, p= 0.013). A multivariate linear regression model revealed that age and spinal cord swelling were independent predictors of MJOA score improvement, explaining 33.2% of the total variation. CONCLUSION: Patients with CSM with spinal cord swelling have less time from symptoms to surgery, and the degree of preoperative neurological deterioration is more obvious. Spinal cord swelling is an independent predictor of surgical prognosis in patients with CSM.

Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions.

Serum amyloid A (SAA) subtypes 1-3 are well-described acute phase reactants that are elevated in acute inflammatory conditions such as infection, tissue injury, and trauma, while SAA4 is constitutively expressed. SAA subtypes also have been implicated as playing roles in chronic metabolic diseases including obesity, diabetes, and cardiovascular disease, and possibly in autoimmune diseases such as systemic lupus erythematosis, rheumatoid arthritis, and inflammatory bowel disease. Distinctions between the expression kinetics of SAA in acute inflammatory responses and chronic disease states suggest the potential for differentiating SAA functions. Although circulating SAA levels can rise up to 1,000-fold during an acute inflammatory event, elevations are more modest (∼5-fold) in chronic metabolic conditions. The majority of acute-phase SAA derives from the liver, while in chronic inflammatory conditions SAA also derives from adipose tissue, the intestine, and elsewhere. In this review, roles for SAA subtypes in chronic metabolic disease states are contrasted to current knowledge about acute phase SAA. Investigations show distinct differences between SAA expression and function in human and animal models of metabolic disease, as well as sexual dimorphism of SAA subtype responses.

Disruption of the early-life microbiota alters Peyer's patch development and germinal center formation in gastrointestinal-associated lymphoid tissue.

During postnatal development, both the maturing microbiome and the host immune system are susceptible to environmental perturbations such as antibiotic use. The impact of timing in which antibiotic exposure occurs was investigated by treating mice from days 5-9 with amoxicillin or azithromycin, two of the most commonly prescribed medications in children. Both early-life antibiotic regimens disrupted Peyer's patch development and immune cell abundance, with a sustained decrease in germinal center formation and diminished intestinal immunoglobulin A (IgA) production. These effects were less pronounced in adult mice. Through comparative analysis of microbial taxa, Bifidobacterium longum abundance was found to be associated with germinal center frequency. When re-introduced to antibiotic-exposed mice, B. longum partially rescued the immunological deficits. These findings suggest that early-life antibiotic use affects the development of intestinal IgA-producing B cell functions and that probiotic strains could be used to restore normal development after antibiotic exposure.

Mid-term low back pain improvement after total hip arthroplasty in 306 patients with developmental dysplasia of the hip.

BACKGROUND: Low back pain (LBP) from hip and spinal disorders has been one of the main reasons for visiting physicians in patients with developmental dysplasia of the hip (DDH). It is essential to identify the LBP improvement among all grades of DDH patients treated with total hip arthroplasty (THA) at 5-year follow-up. METHODS: The study included 407 hips of 306 patients (38 males, 268 females) who underwent THA between July 2007 and December 2016. There were 65 hips in Crowe I, 61 hips in Crowe II, 69 hips in Crowe III, and 212 hips in Crowe IV. One hundred and fourteen hips received subtrochanteric shortening. Patients included 101 bilateral THA (BTHA) and 205 unilateral THA (UTHA). The evaluation was performed through Back Pain Function Scale (BPFS), Harris hip score, Visual Analogue Scale (VAS), operative data and radiographic examinations. RESULTS: The BPFS in patients of unilateral Crowe III and IV relieved significantly more (p < 0.05). However, the BPFS in patients with bilateral symmetry DDH hips relieved significantly less than other groups of DDH hips (p < 0.05). Harris in hips of Crowe II improved significantly more (p < 0.05). The VAS in hips of Crowe II and III improved significantly more (p < 0.05). The unilateral THA surgical time, blood loss, blood transfusion, and osteotomy number and length in Crowe IV were significantly more (p < 0.05). CONCLUSION: THA is reliable to relieve LBP in DDH patients of unilateral Crowe III and IV; however, in patients with unilateral Crowe I, Crowe II, and bilateral DDH hips, the LBP improvements were limited. This should assist shared decision-making between orthopedic surgeons and patients. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Pathogenic mechanism of Eimeria tenella autophagy activation of chicken embryo cecal epithelial cells induced by Eimeria tenella.

Eimeria tenella mainly invades and develops into cecal epithelial cells of chickens, resulting in cecal epithelial cell damage. Infectious intracellular pathogens possibly act by influencing the autophagy process after invading cells. The interaction between E. tenella and the autophagy of host cells was explored by infecting E. tenella with chick embryo cecal epithelial cells. Transmission electron microscopy, laser confocal microscopy, and Western blot analysis were used to demonstrate that E. tenella infection could induce autophagy in host cells. Results showed that infection with E. tenella induced the formation of autophagosomes in cells. The expression of ATG 5, Beclin-1, and LC3B-II proteins were significantly (P < 0.01) increased after E. tenella infected host cells. Expression of p62 protein levels were significantly (P < 0.01) decreased in host cells infected with E. tenella. Chloroquine (CQ) significantly (P < 0.01) increased the expression levels of LC3B-II and P62 in E. tenella-infected host cells. Rapamycin (RAPA) induced autophagy in host cells, thus reducing the intracellular infection of E. tenella. By contrast, the infection rate of E. tenella increased in cells treated with 3-Methyladenine (3-MA). Hence, E. tenella sporozoite infection could induce autophagy activation in chick embryo cecal epithelial cells, and enhanced autophagy could reduce the infection rate of E. tenella.

A biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties and accelerating osseointegration in spinal fusion.

Objectives: Spinal fusion is a widely employed treatment of patients with degenerative disc disease, in which a cage is used to replace the disc for spinal fusion. But it often fails for insufficient mechanical strength and poor osseointegration. Here, we designed a polyether-ether-ketone (PEEK)/tantalum (Ta) composite cage with a biomimetic gradient porous micro-structure, simultaneously enhancing mechanical properties and accelerating osseointegration in spinal fusion. Materials and methods: In the study, based on the mechanical performances of PEEK and osteogenic potential of Ta, and the three-dimensional (3D) structures of cuttlebone and vertebra, the cages were respectively 3D printed by pure PEEK, PEEK with 5 wt% Ta (PEEK/Ta-5), PEEK with 10 wt% Ta (PEEK/Ta-10) and PEEK with 15 wt% Ta (PEEK/Ta-15), then verified in vitro and in sheep cervical fusion model systematically. Results: Vertebral Gyroid structure PEEK/Ta-15 cage exhibited superior mechanical properties than Cuttlebone-like structure PEEK/Ta-15 cage, closer to the cervical vertebra. Furthermore, PEEK/Ta-15 cage with higher Ta microparticles in PEEK provided a biomimetic gradient porous micro-structure with higher surface energy, guiding cell biological behavior, promoting new bone penetration, and accelerating osseointegration in vivo. Conclusion: In conclusion, the study designed a biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties, accelerating osseointegration and forming an anatomical lock in the fusion segment through composites, mechanical efficiency, surface extension, and pores.

Cross-cultural adaptation and validation of the simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire (EILP).

PURPOSE: This study cross-culturally adapted and psychometrically validated a simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire (SC-EILP) for evaluating the severity of symptoms and sports ability among individuals with exercise-induced leg pain. MATERIALS AND METHODS: One hundred and fourteen participants with exercise-induced leg pain were included. To assess reliability, we calculated Cronbach's α and intra-class correlation coefficient (ICC). Construct validity was analysed by assessing the correlations between SC-EILP and visual analogue scale (VAS), University of California Los Angeles activity score (UCLA), and short form (36) health survey (SF-36). Factorial validity was used to establish the factor structure of the questionnaire. RESULTS: The EILP was cross-culturally well-adapted and translated into simplified Chinese. Each item was appropriately correlated with the total items. SC-EILP had nearly good reliability [Cronbach's α = 0.798, ICC = 0.897, 95% confidence interval 0.851-0.929]. The elimination of any one item in all did not result in a value of Cronbach's α of <0.80. SC-EILP had a very good correlation with VAS (-0.607, p < 0.01) and a moderate correlation with UCLA (0.581, p < 0.01) and physical domains of SF-36 (0.499-0.528, p < 0.01). Exploratory factor analysis revealed the 3-factor loading explained 74.736% of the total variance [Kaiser-Mayer-Olkin (KMO) = 0.672, C2 = 665.34, p < 0.001]. CONCLUSIONS: SC-EILP showed excellent acceptability, internal consistency, reliability, and construct validity, and could be recommended for individuals in Mainland China.

This study translated and cross-culturally adapted Exercise-Induced Leg Pain Questionnaire into a Simplified Chinese version, and evaluated its reliability and validity in individuals with exercise-induced leg pain.Moderate to substantial correlations between the Simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire and VAS, UCLA, as well as physical subscales of SF-36 were observed.Exploratory factor analysis revealed that the 3-factor loading explained 74.736% of the total variance [Kaiser­Mayer­Olkin (KMO) = 0.672, C² = 665.34, p < 0.001].Simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire was demonstrated to have acceptable simplicity, good reliability, and validity in individuals with exercise-induced leg pain, which could be recommended for patients in Chinese mainland.

Mid-term outcomes after total hip arthroplasty in 106 Crowe II/III hips: different hip center positions.

BACKGROUND: Under the obvious acetabular superolateral bone defect of Crowe II/III hips, this study aimed to investigate the difference in surgical technique of different hip center positions from the surgical data and clinical outcomes. METHODS: From July 2007 to December 2016, 87 patients (106 Crowe II/III hips) consecutively received total hip arthroplasty (THA). The minimum follow-up time was 5 years. The mean limb length discrepancy was 1.97 ± 1.81 cm. Twenty-four hips had surgical histories. The patients were divided into three groups according to the acetabular prosthesis positions, depending on the Crowe classification, respectively, group 1 (Crowe I), group 2 (Crowe II) and group 3 (Crowe III). The surgical data and clinical results were used to evaluate the outcome of different surgical techniques of different hip center positions, including surgical time, blood loss, blood transfusion, number of osteotomy hips, osteotomy length, the distribution of prothesis, postoperative inpatient days, Harris hip scores, Visual Analogue Scale (VAS), Back Pain Function Scale (BPFS) and complications. RESULTS: The mean follow-up time was 8.93 ± 2.55 years. Nineteen hips performed intraoperative osteotomy. From group 1 to group 3, the mean osteotomy length were 0.53 ± 1.11 cm, 0.05 ± 0.22 cm, and 0.00 ± 0.00 cm, respectively (p = 0.083); the surgical time were 142.57 ± 57.94 min, 118.4 ± 41.22 min, and 120.00 ± 84.85 min, respectively (p = 0.324); the blood loss were 498.21 ± 368.53 mL, 333.33 ± 167.62 mL, and 350.00 ± 212.13 mL, respectively (p = 0.255); the blood transfusion were 288.48 ± 381.68 mL, 128.00 ± 235.17 mL, and 385.00 ± 219.20 mL, respectively (p = 0.199); the postoperative inpatient days were 7.95 ± 4.42 d, 7.47 ± 4.29 d, and 6.50 ± 0.71 d, respectively (p = 0.831). Among the groups, the distribution of acetabular prosthesis, acetabular liner, acetabular prosthesis sizes, femoral head sizes and femoral prothesis distal sizes were not significantly different (p > 0.05). Only the distribution of femoral prosthesis was significantly different (p = 0.046); the Harris, VAS, BPFS, and the distribution of complications were not significantly different (p > 0.05). CONCLUSIONS: We provided a framework to guide decision-making in Crowe II/III hips for surgeons: the surgical technique of different hip center positions was stable and had good outcomes, but the acetabular prothesis position and femoral prothesis should be determined according to the intraoperative situation. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Retroperitoneal leiomyoma located in the broad ligament: A case report.

BACKGROUND: Retroperitoneal leiomyoma is a rare benign tumor. Retroperitoneal leiomyomas located in the latissimus uterine ligament are even rarer. Retroperitoneal leiomyomas have similar characteristics to uterine leiomyomas in terms of tissue, which results in confusion during diagnosis. CASE SUMMARY: A 47-year-old female with 3 years of pain in the right lower quadrant and discovery of a pelvic mass 13 d ago underwent open abdominal exploration. In the right broad ligament, a solid mass with well circumscribed boundaries, approximately 15 cm × 10 cm × 10 cm in size was bluntly peeled off. The pathological result was a spindle cell tumor, morphologically considered to originate from smooth muscle. Immunohistochemical results supported a deep soft tissue leiomyoma. CONCLUSION: Retroperitoneal leiomyoma is a rare benign tumor, and surgical treatment can have a good therapeutic effect.

Role of EtMIC4 EGF-like in regulating the apoptosis of Eimeria tenella host cells via the EGFR pathway.

This study aimed to explore the role and key point of EtMIC4 EGF-like recombinant protein in regulating the apoptosis of Eimeria tenella host cells via the epidermal growth factor receptor (EGFR) pathway. The cells were treated with EtMIC4 EGF-like protein, EGFR-specific siRNA, or both. Infection and apoptosis rates as well as dynamic changes in the key genes and proteins of the EGFR signaling pathway in the host cells were determined. Results showed that the E. tenella and EtMIC4 EGF-like group had the highest infection rate (P < 0.01). In cells treated with EtMIC4 EGF-like for 4 to 24 h, the apoptosis rate was significantly decreased (P < 0.01) and the relative mRNA expression and protein phosphorylation levels of EGFR, protein kinase B (AKT), and extracellular regulated protein kinases (ERK) were significantly increased (P < 0.01). In E. tenella sporozoites infected for 4 to 96 h, the rate of host cell apoptosis induced by E. tenella infection was significantly (P < 0.01) reduced by EtMIC4 EGF-like. The relative mRNA expression and protein phosphorylation levels of EGFR, AKT, and ERK in the host cells of E. tenella + EtMIC4 EGF-like group were significantly increased (P < 0.01). These results indicated that E. tenella could activate the EGFR pathway through EtMIC4 EGF-like and regulate the expression of key genes in the AKT and ERK signaling pathways, thereby inhibiting cell apoptosis.

The role of Ca2+ in the injury of host cells during the schizogenic stage of E. tenella.

Cecal epithelial cell damage is a key factor in host injure during the development of E. tenella. The intracellular free Ca2+ of the host cell is closely related to the invasion, development and proliferation of intracellular parasites, and cell damage. To determine the relationship between Ca2+ and host cell damage in the schizogenic stage of E. tenella, we established a chick embryo cecal epithelial cells model of E. tenella infection. Fluorescence staining, flow cytometry, transmission electron microscopy, inhibition and blocking experiments were used to detect the damage effect and mechanism of host cells during the schizogenic stage of E. tenella. The results showed that the host cells cytoskeletal remodeling, cell and organelle structure was destroyed, and apoptosis and necrosis were increased during the schizont stage of E. tenella. Furthermore, the above-mentioned effects of the schizogenic stage of E. tenella on cells can be alleviated by reducing the intracellular Ca2+ concentration in the host cells. These observations indicate that the effect of host cell injury was closely related to Ca2+ during schizont stage of E. tenella.

Critical assessment of DNA adenine methylation in eukaryotes using quantitative deconvolution.

The discovery of N6-methyldeoxyadenine (6mA) across eukaryotes led to a search for additional epigenetic mechanisms. However, some studies have highlighted confounding factors that challenge the prevalence of 6mA in eukaryotes. We developed a metagenomic method to quantitatively deconvolve 6mA events from a genomic DNA sample into species of interest, genomic regions, and sources of contamination. Applying this method, we observed high-resolution 6mA deposition in two protozoa. We found that commensal or soil bacteria explained the vast majority of 6mA in insect and plant samples. We found no evidence of high abundance of 6mA in Drosophila, Arabidopsis, or humans. Plasmids used for genetic manipulation, even those from Dam methyltransferase mutant Escherichia coli, could carry abundant 6mA, confounding the evaluation of candidate 6mA methyltransferases and demethylases. On the basis of this work, we advocate for a reassessment of 6mA in eukaryotes.

Simplified Chinese Version of the Back Pain Function Scale (BPFS) for Patients with Low Back Pain: Cross-Cultural Adaptation and Validation.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To translate and cross-culturally adapt back pain function scale (BPFS) into a simplified Chinese version (SC-BPFS), and evaluate the reliability and validity of SC-BPFS in patients with low back pain. SUMMARY OF BACKGROUND DATA: The BPFS is a reliable and valid evaluation instrument for low back pain. However, simplified Chinese version of BPFS has not been validated. METHODS: Cross-cultural adaptation was performed according to the internationally recognized guidelines of the American Academy of Orthopaedic Surgeons Outcome Committee. One-hundred and sixty-two participants with low back pain (LBP) were included in this study. Reliability was tested based on test-retest reliability and internal consistency. We calculated Cronbach alpha and intra-class correlation coefficient (ICC). Construct validity was analyzed by evaluating the correlations between SC-BPFS and the Oswestry disability index (ODI), the visual analogue scale (VAS), and the short form (36) health survey (SF-36). RESULTS: The original version of the BPFS was cross-culturally well adapted and translated into simplified Chinese. Each item of the SC-BPFS was properly responded and correlated with the total items. SC-BPFS had good reliability (Cronbach alpha = 0.847, intra-class correlation coefficient [ICC] = 0.891, 95% confidence interval [CI] 0.864-0.914). Elimination of any one item in all did not result in a value of Cronbach alpha of <0.80. SC-BPFS had a high correlation with ODI (0.712, P < 0.01) and a moderate correlation with VAS (0.484, P < 0.01). And it was also fairly to very well correlated with physical domains of SF-36 (0.334-0.632, P < 0.01), and not correlated with mental domains of SF-36 (0.022-0.119, P > 0.05). CONCLUSION: SC-BPFS demonstrated outstanding acceptability, internal consistency, reliability, and construct validity, and could be recommended for patients with LBP in Mainland China.Level of Evidence: 3.

A simple, universal and multifunctional template agent for personalized treatment of bone tumors.

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved.