Correlation between bone density, bone metabolism markers with lipid metabolism markers and body mass index.

PURPOSE: We aimed to explore the relationship between bone mineral density (BMD), bone metabolism markers, and blood lipid-related indicators, body mass index (BMI) in elderly individuals. METHODS: A retrospective analysis was conducted on 710 patients. Patients' gender, age, height, weight, bone density values, T-scores, bone metabolism markers (including serum N-terminal propeptide of type I collagen (s-PINP), serum C-terminal telopeptide of type I collagen (s-CTX) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and lipid-related indicators (including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and Castelli index 1 (TC/HDL-C index) and Castelli index 2 (LDL-C/HDL-C index) were recorded. Correlations between variables were analyzed, and patients were grouped according to gender and T-score for intergroup comparisons. RESULTS: HDL-C negatively correlates with BMD and s-CTX. TG, Castelli index, and BMI positively correlate with BMD. BMI negatively correlates with s-PINP. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. LDL-C positively correlates with BMD in males, and TC negatively correlates with s-PINP. In females, HDL-C negatively correlates with BMD, and s-CTX positively correlates with Castelli index. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. TG and Castelli index were higher in normal bone mass group, while HDL-C is higher in the osteoporosis group. TG and BMI positively predicted bone mass density, while HDL-C negatively predicted bone mass density. CONCLUSIONS: HDL-C may have a predictive role in osteoporosis, particularly in women. The likelihood of osteoporosis is lower in individuals with high BMI or hyperlipidemia. Some lipid metabolism markers can be used to predict osteoporosis, and further research is needed.

Paternal high-fat diet altered H3K36me3 pattern of pre-implantation embryos.

The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.

Clinical efficacy and influencing factors of percutaneous kyphoplasty for osteoporotic vertebral compression fractures: a 10-year follow-up study.

BACKGROUND: To date, few reports have evaluated the long-term outcome of percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and the factors influencing the long-term outcome of this procedure are uncertain. METHODS: A total of 91 patients underwent PKP for thoracolumbar OVCFs from June 2012 to December 2012. Pain Visual Analogue Scores (VAS) and Oswestry Disability Index (ODI) were recorded preoperatively and after 10-year follow-up. Factors that may affect surgical outcome, such as gender, age, height, weight, hypertension, diabetes, cause of injury, fracture segment, length of hospitalization, history of previous spinal surgery, preoperative bone mineral density (BMD), preoperative VAS and ODI scores, length of surgery, bone cement dosage, postoperative standardized anti-osteoporosis treatment, and other new vertebral fractures, were analyzed by multiple linear regression with VAS and ODI scores at the last follow-up. The correlation factors affecting the efficacy were analyzed. RESULTS: The preoperative and final follow-up pain VAS was 7.9 ± 1.1 and 2.2 ± 1.1. ODI scores were 30.4 ± 4.2 and 10.7 ± 2.6. The difference was statistically significant (P < 0.05). Most of the patients were females aged 65-75 years who suffered low-energy injuries, with most of the fracture segments in the thoracolumbar region (T11-L2). At the final follow-up visit, 12 cases (13.19%) developed other new vertebral fractures, and 33 cases (36.26%) continued to adhere to anti-osteoporosis treatment after discharge. Multiple linear regression analysis showed that there was a statistical difference between gender and VAS score at the last follow-up (P < 0.05), and between age, cause of injury and postoperative standardized anti-osteoporosis treatment and ODI at the last follow-up (P < 0.05). There were no statistically significant differences between the other factors and the final follow-up VAS and ODI scores (P > 0.05). CONCLUSION: The long-term outcome after PKP is satisfactory. Age, gender, cause of injury, and standardized postoperative anti-osteoporosis treatment may be factors affecting the long-term outcome.

Long Noncoding RNA MAGI2-AS3 Represses Cell Progression in Clear Cell Renal Cell Carcinoma by Modulating the miR-629-5p/PRDM16 Axis.

The objective of this study was to determine the regulatory mechanism of MAGI2-AS3 in clear cell renal cell carcinoma (ccRCC), thereby supplying a new insight for ccRCC treatment. Expression data in TCGA-KIRC were obtained. Target gene lncRNA for research was determined using expression analysis and clinical analysis. lncRNA's downstream regulatory miRNA and mRNA were predicted by bioinformatics databases. ccRCC cell malignant phenotypes were detected via CCK-8, colony formation, Transwell migration, and invasion assays. The targeting relationship between genes was assessed through dual-luciferase reporter gene analysis. Kaplan-Meier (K-M) analysis was carried out to verify the effect of MAGI2-AS3, miR-629-5p, and PRDM16 on the survival rate of ccRCC patients. MAGI2-AS3 expression in ccRCC tissue and cells was shown to be markedly decreased and its expression to continuously decline with tumor progression. MAGI2-AS3 suppresses ccRCC proliferation and migration. Dual-luciferase assay showed that MAGI2-AS3 binds miR-629-5p and that miR-629-5p binds PRDM16. In addition, functional experiments showed that MAGI2-AS3 facilitates PRDM16 expression by repressing miR-629-5p expression, thereby suppressing ccRCC cell aggression. K-M analysis showed that upregulation of either MAGI2-AS3 or PRDM16 significantly improves ccRCC patient survival, while upregulation of miR-629-5p has no significant impact. MAGI2-AS3 sponges miR-629-5p to modulate PRDM16 to mediate ccRCC development. Meanwhile, the MAGI2-AS3/miR-629-5p/PRDM16 axis, as a regulatory pathway of ccRCC progression, may be a possible therapeutic target and prognostic indicator of ccRCC.

OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy in diffuse large B-cell lymphoma.

OX40 enhances the T-cell activation via costimulatory signaling. However, its molecular characteristics and value in predicting response to immunochemotherapy in DLBCL remain largely unexplored. Here, we performed an integrative analysis of sequencing and multiplex immunofluorescence staining, and discovered abnormally higher expression of OX40 in DLBCL patients. Elevated OX40 could activate T cells leading to a higher immune score for tumor immune microenvironment (TiME). OX40 upregulation simultaneously happened with immune-related genes including PD-1, CTLA4 and TIGIT et,al. Patients with high OX40 expression exhibited a lower Ann Arbor stage and IPI score and more easily achieved a complete response/partial response. The analysis of infiltrated T-cell subset revealed that patients with a greater number of CD4+/OX40+ or CD8+/OX40+ T cells had a longer OS. Our findings indicated that OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy, providing insights for the application of OX40 agonist in DLBCL patients.

Integrative genomic and transcriptomic analysis reveals genetic alterations associated with the early progression of follicular lymphoma.

Follicular lymphoma (FL), the most common indolent lymphoma, is a clinically and genetically heterogeneous disease. However, the prognostic value of driver gene mutations and copy number alterations has not been systematically assessed. Here, we analysed the clinical-biological features of 415 FL patients to identify variables associated with disease progression within 24 months of first-line therapy (POD24). Patients with B symptoms, elevated lactate dehydrogenase and ß2-microglobulin levels, unfavourable baseline haemoglobin levels, advanced stage, and high-risk FL International Prognostic Index (FLIPI) scores had an increased risk of POD24, with FLIPI being the most important factor in logistic regression. HIST1H1D, identified as a driver mutation, was correlated with POD24. Gains of 6p22.2 (HIST1H1D) and 18q21.33 (BCL2) and loss of 1p36.13 (NBPF1) predicted POD24 independent of FLIPI. Gene expression profiling of FL samples showed that the POD24 cohort was significantly enriched in the inflammatory response (mediated by interferon and tumour necrosis factor), cell cycle regulation (transcription, replication and proliferation) sets and PI3K-AKT-mTOR signalling. This result was further validated with transcriptome-wide information provided by RNA-seq at single-cell resolution. Our study, performed on a large cohort of FL patients, highlights the importance of distinctive genetic alterations and gene expression relevant to disease diagnosis and early progression.

Exploring the molecular characteristics of the malignant potential of gastric adenocarcinoma with enteroblastic differentiation.

AIMS: Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subset of alpha-fetoprotein (AFP)-producing carcinomas with poor prognosis. However, the molecular features associated with the malignant potential of GEAD remain partially elucidated. METHODS AND RESULTS: In this study, the relationship between clinicopathological parameters and aggressive biological behaviour was analysed in 37 patients with GAED. The results showed that GAED tended to infiltrate the deep layer of the gastric wall and possessed more frequent vascular invasion than conventional gastric adenocarcinoma (CGA) (P < 0.001). All distant metastases were observed in the GAED group, not the CGA group (P < 0.001). High HER2 expression was found in nearly 24.32% of the informative cases, and none showed EBV-encoded RNA positivity or deficient mismatch repair. The most frequently mutated gene in GAED was p53. Programmed cell death-ligand 1 (PD-L1) immunostaining revealed 13 patients with a combined positive score (CPS) ≥ 5 (65%, 13 of 20). Thus, based on these molecular markers (immunostaining, in situ hybridisation and mutation analysis), GAED may be classified as a unique subgroup of the chromosomal instability subtype with HER2+ /EBV- /MSS/TP53+ /PD-L1+ . Next-generation sequencing analyses showed that mutations in the TOPI, ELOA and NOTCH3 genes were found only in GAED, and abnormally expressed genes in GAED were significantly enriched in hepatocellular carcinoma-, gland development-, and gastric cancer-related pathways. CONCLUSION: The HER2+ /EBV- /MSS/TP53+ /PD-L1+ profile and hepatocellular carcinoma-related pathways may be significant in the malignant potential of GAED. In addition to anti-HER2 therapy, immune check-point inhibitors may be an effective treatment option for patients with GAED.

Significant alteration of protein profiles in a mouse model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disorder, affecting women of child-bearing age, and the incidence rate is growing and assuming epidemic proportions. The etiology of PCOS remains unknown and there is no cure. Some animal models for PCOS have been established which have enhanced our understanding of the underlying mechanisms, but omics data for revealing PCOS pathogenesis and for drug discovery are still lacking. In the present study, proteomics analysis was used to construct a protein profile of the ovaries in a PCOS mouse model. The result showed a clear difference in protein profile between the PCOS and control group, with 495 upregulated proteins and 404 downregulated proteins in the PCOS group. The GO term and KEGG pathway analyses of differentially expressed proteins mainly showed involvement in lipid metabolism, oxidative stress, and immune response, which are consistent with pathological characteristics of PCOS in terms of abnormal metabolism, endocrine disorders, chronic inflammation and imbalance between oxidant and antioxidant levels. Also, we found that inflammatory responses were activated in the PCOS ovarium, while lipid biosynthetic process peroxisome, and bile secretion were inhibited. In addition, we found some alteration in unexpected pathways, such as glyoxylate and dicarboxylate metabolism, which should be investigated. The present study makes an important contribution to the current lack of PCOS ovarian proteomic data and provides an important reference for research and development of effective drugs and treatments for PCOS.

proBDNF/p75NTR promotes rheumatoid arthritis and inflammatory response by activating proinflammatory cytokines.

P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4+ and CD8+ T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA.

High-Efficiency ZnS: Cu+, Al3+ Scintillator for X-ray Detection in a Non-Darkroom Environment.

Scintillator is a key component in X-ray detectors that determine the performance of the devices. Nevertheless, due to the interference of the ambient light sources, scintillators are only operated in a darkroom environment currently. In this study, we designed a Cu+ and Al3+ co-doped ZnS scintillator (ZnS: Cu+, Al3+) that introduces donor-acceptor (D-A) pairs for X-ray detection. The prepared scintillator displayed an extremely high steady-state light yield (53,000 photons per MeV) upon X-ray irradiation, which is 5.3 times higher than that of the commercial Bi4Ge3O12 (BGO) scintillator, making it possible in X-ray detection with the interference of ambient light. Furthermore, the prepared material was employed as a scintillator to construct an indirect X-ray detector, which performed a superior spatial resolution (≈10.0 lp/mm) as well as persistent stability under visible light interference, demonstrating the feasibility of the scintillator in practical applications. Therefore, this research presented a convenient and useful strategy to realize X-ray detection in a non-darkroom environment.

A Case-Control Study of 40 Patients with Piriformis Muscle Syndrome to Evaluate Diagnostic Findings Using Two-Dimensional Ultrasound and Shear Wave Elastography.

BACKGROUND Piriformis muscle syndrome (PMS) is a neuropathy caused by compression of the sciatic nerve by the piriformis muscle. This case-control study included 40 patients with PMS and aimed to evaluate the diagnostic findings using two-dimensional ultrasound and shear wave elastography (SWE), as non-invasive and cost-effective diagnostic methods. MATERIAL AND METHODS In order to evaluate the value of two-dimensional ultrasound diagnosis, a new imaging technique called shear wave elastography (SWE) was used in the screening of PMS, with a total of 40 PMS patients and 40 healthy individuals participating in our study. We analyzed the correlation and area under the curve (AUC) of changes in thickness (mm) and Young's modulus (kpa) of the bilateral piriformis muscle (PM). RESULTS We found that PM thickness and Young's modulus on the lesion sides were significantly higher in PMS patients than in controls (P<0.05). Also, we determined that there was a positive correlation between PM thickness and Young's modulus (r=0.454, P<0.05). Using two-dimensional ultrasonic diagnosis and the SWE technique, a specificity of 95.8% and sensitivity of 78.8% were demonstrated in the clinical diagnosis of PM. CONCLUSIONS Two-dimensional ultrasound with SWE technology has demonstrated its superior sensitivity and specificity in diagnosing PMS in the clinic.

Generation of a Predictive Clinical Model for Isolated Distal Deep Vein Thrombosis (ICMVT) Detection.

BACKGROUND Isolated distal deep vein thrombosis (ICMVT) increases the risk of pulmonary embolism. Although predictive models are available, their utility in predicting the risk is unknown. To develop a clinical prediction model for isolated distal calf muscle venous thrombosis, data from 462 patients were used to assess the independent risk variables for ICMVT. MATERIAL AND METHODS The area under curve (AUC) for Model A and Model B were calculated and other risk factors were based on age, pitting edema in the symptomatic leg, calf swelling with least 3 cm larger than the asymptomatic leg, recent bed rest for 3 days or more in the past 4 weeks, requiring general or major surgery with regional anesthesia, sex, and local tenderness distributed along the deep venous system as independent predictors of calf muscle venous thrombosis. Model A includes the risk variables for C-reactive protein and D-dimer. RESULTS The area under ROC curve for Model A training set was 0.924 (95% CI: 0.895-0.952), the area under ROC curve for Model B training set was 0.887 (95% CI: 0.852-0.922), and the AUC difference between the 2 models was statistically significant (P<0.001); the area under ROC curve for Model A obtained in the validation set was 0.902 (95% CI: 0.844-0.961), the area under ROC curve for Model B was 0.842 (95% CI: 0. 0.773-0.910), and the difference between the 2 models was statistically significant (P=0.012). CONCLUSIONS Predictive Model A better predicts isolated calf muscle venous thrombosis and is able to help clinicians rapidly and early diagnose ICMVT, displaying higher utility for missed diagnosis prevention and disease therapy.

Long non-coding RNA LINC00565 regulates ADAM19 expression through sponging microRNA-532-3p, thereby facilitating clear cell renal cell carcinoma progression.

Proven by publications, long non-coding RNAs (lncRNAs) play critical roles in the development of clear cell renal cell carcinoma (ccRCC). Although lncRNA LINC00565 has been implicated in the progression of various cancers, its biological effects on ccRCC remain unknown. This study aimed to investigate the biological functions of LINC00565, as well as its potential mechanism in ccRCC. Here, the expression data of mature microRNAs (miRNAs) (normal: 71, tumor: 545), messenger RNAs (mRNAs), and lncRNAs (normal: 72, tumor: 539) of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database and subjected to differential expression analysis. Quantitative reverse transcriptase polymerase chain reaction analyzed the expression levels of LINC00565, miR-532-3p, and ADAM19 mRNA. TCGA database, dual-luciferase report detection, and Argonaute 2 RNA immunoprecipitation were utilized to confirm the relationships between LINC00565 and miR-532-3p and between miR-532-3p and ADAM19, respectively. The progression of ccRCC cells was determined via CCK-8, colony formation, scratch healing, and transwell assays. Western blot was applied to detect the protein levels of epithelial-mesenchymal transition markers and ADAM19. We herein suggested that LINC00565 was prominently upregulated in ccRCC tissues and cells. Knockdown of LINC00565 repressed cell progression. We further predicted and validated miR-532-3p as a target of LINC00565, and miR-532-3p could target ADAM19. Knockdown of LINC00565 resulted in ADAM19 level downregulation in ccRCC cells and suppressed miR-532-3p could restore ADAM19 level. Thus, the three RNAs constructed a ceRNA network. Overexpressed ADAM19 could eliminate the anticancer effects caused by knocking down LINC00565 on ccRCC cells. In conclusion, LINC00565 upregulated ADAM19 via absorbing miR-532-3p, thereby facilitating the progression of ccRCC cells.

An Amorphous n-Type Conjugated Polymer with an Ultra-Rigid Planar Backbone.

High charge carrier mobility polymer semiconductors are always semi-crystalline. Amorphous conjugated polymers represent another kind of polymer semiconductors with different charge transporting mechanism. Here we report the first near-amorphous n-type conjugated polymer with decent electron mobility, which features a remarkably rigid, straight and planar polymer backbone. The molecular design strategy is to copolymerize two fused-ring building blocks which are both electron-accepting, centrosymmetrical and planar. The polymer is the alternating copolymer of double B←N bridged bipyridine (BNBP) unit and benzobisthiazole (BBTz) unit. It shows a decent electron mobility of 0.34 cm2  V-1 s-1 in organic field-effect transistors. The excellent electron transporting property of the polymer is possibly due to the ultrahigh backbone stiffness, small π-π stacking distance, and high molecular weight.

An n-Type Polythiophene Derivative with Excellent Thermoelectric Performance.

Typical n-type conjugated polymers are based on fused-ring electron-accepting building blocks. Herein, we report a non-fused-ring strategy to design n-type conjugated polymers, i.e. introducing electron-withdrawing imide or cyano groups to each thiophene unit of a non-fused-ring polythiophene backbone. The resulting polymer, n-PT1, shows low LUMO/HOMO energy levels of -3.91 eV/-6.22 eV, high electron mobility of 0.39 cm2  V-1 s-1 and high crystallinity in thin film. After n-doping, n-PT1 exhibits excellent thermoelectric performance with an electrical conductivity of 61.2 S cm-1 and a power factor (PF) of 141.7 µW m-1 K-2 . This PF is the highest value reported so far for n-type conjugated polymers and this is the first time for polythiophene derivatives to be used in n-type organic thermoelectrics. The excellent thermoelectric performance of n-PT1 is due to its superior tolerance to doping. This work indicates that polythiophene derivatives without fused rings are low-cost and high-performance n-type conjugated polymers.

Sperm-borne proteins improve rabbit cloning efficiency via regulating embryonic cleavage and epigenetics.

Somatic cell nuclear transfer (SCNT) shows great application value in the generation of transgenic animals, protection of endangered species, and therapeutic cloning. However, the cloning efficiency is still very low, which greatly restricts its application. Compared to fertilized embryos, cloned embryos lack the sperm proteins, which are considered to play an important role in embryonic development. Here, we compared the sperm proteome, with that of donor fibroblasts and oocytes, and identified 342 proteins unique to sperm, with 42 being highly expressed. The 384 proteins were mainly enriched in the categories of post-translational modification and cytoskeletal arrangement. Extracts of soluble sperm or fibroblast proteins were injected into cloned embryos, and the result showed that injection of sperm protein significantly inhibited abnormal embryonic cleavage, significantly decreased the level of trimethylated histone H3 Lys9 (H3K9me3) and the apoptotic index, and increased the inner cell mass (ICM)-to-trophectoderm (TE) ratio. More importantly, the sperm proteins also significantly enhanced the birthrate. The results of in vitro and in vivo experiments demonstrate that sperm-derived proteins improve embryo cloning efficiency. Our findings not only provide new insights into ways to overcome low cloning efficiency, but also add to the understanding of sperm protein function.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Among Air Passengers in China.

BACKGROUND: Modern transportation plays a key role in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and new variants. However, little is known about the exact transmission risk of the virus on airplanes. METHODS: Using the itinerary and epidemiological data of coronavirus disease 2019 (COVID-19) cases and close contacts on domestic airplanes departing from Wuhan city in China before the lockdown on 23 January 2020, we estimated the upper and lower bounds of overall transmission risk of COVID-19 among travelers. RESULTS: In total, 175 index cases were identified among 5797 passengers on 177 airplanes. The upper and lower attack rates (ARs) of a seat were 0.60% (34/5622, 95% confidence interval [CI] .43-.84%) and 0.33% (18/5400, 95% CI .21-.53%), respectively. In the upper- and lower-bound risk estimates, each index case infected 0.19 (SD 0.45) and 0.10 (SD 0.32) cases, respectively. The seats immediately adjacent to the index cases had an AR of 9.2% (95% CI 5.7-14.4%), with a relative risk 27.8 (95% CI 14.4-53.7) compared to other seats in the upper limit estimation. The middle seat had the highest AR (0.7%, 95% CI .4%-1.2%). The upper-bound AR increased from 0.7% (95% CI 0.5%-1.0%) to 1.2% (95% CI .4-3.3%) when the co-travel time increased from 2.0 hours to 3.3 hours. CONCLUSIONS: The ARs among travelers varied by seat distance from the index case and joint travel time, but the variation was not significant between the types of aircraft. The overall risk of SARS-CoV-2 transmission during domestic travel on planes was relatively low. These findings can improve our understanding of COVID-19 spread during travel and inform response efforts in the pandemic.

A novel immune-related epigenetic signature based on the transcriptome for predicting the prognosis and therapeutic response of patients with diffuse large B-cell lymphoma.

Epigenetic modifications contribute to lymphomagenesis. Here, we performed an expression clustering analysis and identified two epigenetic-related clusters (EC1 and EC2). EC1 presented abundant TP53, MYD88, HIST1H1D, HIST1H1C, KMT2D and EZH2 mutations and an inferior prognosis. Pathways involved in the regulation of DNA methylation/demethylation, histone methyltransferase activity, and protein methyltransferase activity were significantly enriched in EC1. However, EC2 was frequently accompanied by B2M, CD70 and MEF2B mutations, which presented with enrichments in DNA damage repair, cytokine-mediated and B-cell activated immune signaling, increased levels of CD8+ T-, γδT- and T helper-cells, as well as immune scores and immunogenic cell death (ICD) modulators. According to the prediction, EC1 was more sensitive to vorinostat, serdemetan and navitoclax. However, ruxolitinib, cytarabine and CP466722 were more suitable treatments for EC2. The novel immune-related epigenetic signature exhibits promising clinical predictive value for diffuse large B-cell lymphoma (DLBCL), particularly for guiding epigenetic therapeutic regimens. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) based combination treatment regimens are suggested.

Tracking the evolution of untreated high-intermediate/high-risk diffuse large B-cell lymphoma by circulating tumour DNA.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogenous malignancy, early identification of patients for relapse remains challenging. The potential to non-invasively monitor tumour evolutionary dynamics of DLBCL needs to be further established. In the present study, 17 tumour biopsy and 38 plasma samples from 38 patients with high-intermediate/high-risk DLBCL were evaluated at baseline. Longitudinal blood samples were also collected during therapy. Circulating tumour DNA (ctDNA) was analysed using targeted sequencing based on a gene panel via a recently developed methodology, circulating single-molecule amplification and re-sequencing technology (cSMART). We found that the most frequently mutated genes were tumour protein p53 (TP53; 42·1%), histone-lysine N-methyltransferase 2D (KMT2D; 28·9%), caspase recruitment domain family member 11 (CARD11; 21·1%), cAMP response element-binding protein binding protein (CREBBP; 15·8%), ß2 -microglobulin (B2M; 15·8%), and tumour necrosis factor alpha-induced protein 3 (TNFAIP3; 15·8%). The mutation profiles between ctDNA and matched tumour tissue showed good concordance; however, more mutation sites were detected in ctDNA samples. Either TP53 or B2M mutations before treatment predicted poor prognosis. Analysis of dynamic blood samples confirmed the utility of ctDNA for the real-time assessment of treatment response and revealed that the increases in ctDNA levels and changes in KMT2D mutation status could be useful predictors of disease progression. Our present results suggest that ctDNA is a promising method for the detection of mutation spectrum and serves as a biomarker for disease monitoring and predicting clinical recurrence.

Role of cassava CC-type glutaredoxin MeGRXC3 in regulating sensitivity to mannitol-induced osmotic stress dependent on its nuclear activity.

BACKGROUND: We previously identified six drought-inducible CC-type glutaredoxins in cassava cultivars, however, less is known about their potential role in the molecular mechanism by which cassava adapted to abiotic stress. RESULTS: Herein, we investigate one of cassava drought-responsive CC-type glutaredoxins, namely MeGRXC3, that involved in regulation of mannitol-induced inhibition on seed germination and seedling growth in transgenic Arabidopsis. MeGRXC3 overexpression up-regulates several stress-related transcription factor genes, such as PDF1.2, ERF6, ORA59, DREB2A, WRKY40, and WRKY53 in Arabidopsis. Protein interaction assays show that MeGRXC3 interacts with Arabidopsis TGA2 and TGA5 in the nucleus. Eliminated nuclear localization of MeGRXC3 failed to result mannitol-induced inhibition of seed germination and seedling growth in transgenic Arabidopsis. Mutation analysis of MeGRXC3 indicates the importance of conserved motifs for its transactivation activity in yeast. Additionally, these motifs are also indispensable for its functionality in regulating mannitol-induced inhibition of seed germination and enhancement of the stress-related transcription factors in transgenic Arabidopsis. CONCLUSIONS: MeGRXC3 overexpression confers mannitol sensitivity in transgenic Arabidopsis possibly through interaction with TGA2/5 in the nucleus, and nuclear activity of MeGRXC3 is required for its function.