Efficacy of venetoclax and rituximab in the treatment of concurrent acute myeloid leukemia and untreated chronic lymphocytic leukemia: A case report and literature review.

To date, few cases of concurrent acute myeloid leukemia (AML) and untreated chronic lymphocytic leukemia (CLL) have been reported. Due to the complexity of the pathogenesis and the absence of a uniform treatment regimen, the associated prognosis remains poor. The present study reports the case of a 58-year-old male with asymptomatic leukocytosis, who was previously healthy with no malignancies. Flow cytometry analysis revealed protocytosis, monocytosis and monoclonal B lymphocytosis in a bone marrow specimen. Results of a gene rearrangement assay demonstrated positive immunoglobulin heavy-chain variable region gene status in monoclonal B lymphocytes. Thus, the patient was diagnosed with AML with maturation (AML-M2) that co-existed with untreated CLL. The normative daunorubicin (40 mg/m2 on days 1-3) and cytarabine (80 mg/m2 on days 1-7) regimen combined with venetoclax (400 mg on days 1-7) and rituximab (375 mg/m2 on day 0) was used as induction chemotherapy. The patient achieved morphological complete remission in both AML and CLL following the first course of chemotherapy. In addition, the present study retrospectively analyzed the data of 22 patients with concurrent AML and untreated CLL, and the results demonstrated that the median age at the time of AML diagnosis was 69 years (range, 52-86 years). Moreover, the male:female ratio was 6.33:1 and AML-M2 was the most frequent subtype at diagnosis. The presence of a complex karyotype was associated with the poorest prognosis, and patients who received venetoclax often exhibited an improved prognosis. In conclusion, the combination of venetoclax and rituximab improves the prognosis of patients with concurrent AML and untreated CLL.

Using sustained vowels to identify patients with mild Parkinson's disease in a Chinese dataset.

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≤ 1.5. Method: We used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≤ 1.5). The models were independently validated using separate datasets. Results: Our results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≤ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75. Conclusion: The results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment.

PREB inhibits the replication of prototype foamy virus by affecting its transcription.

BACKGROUND: Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV-host cell interactions and the molecular mechanisms underlying FV latent infection. METHODS: We used the prototype FV (PFV) to infect HT1080 cells and a PFV indicator cell line (PFVL) to measure virus titers. After 48 h of infection, the culture supernatant (i.e., cell-free PFV particles) and transfected cells (i.e., cell-associated PFV particles) were harvested and incubated with PFVL. After another 48 h, the luciferase activity was used to measure virus titers. RESULTS: Through transcriptomics sequencing, we found that PREB mRNA expression was significantly upregulated. Moreover, PREB overexpression reduced PFV replication, whereas endogenous PREB knockdown increased PFV replication. PREB interacted with the Tas DNA-binding and transcriptional activation domains and interfered with its binding to the PFV long terminal repeat and internal promoter, preventing the recruitment of transcription factors and thereby inhibiting the transactivation function of Tas. PREB C-terminal 329-418 aa played a major role in inhibiting PFV replication; PREB also inhibited bovine FV replication. Therefore, PREB has a broad-spectrum inhibitory effect on FV replication. CONCLUSIONS: Our results demonstrated that PREB inhibits PFV replication by impeding its transcription.

Gene Expression and Interaction Analysis of FsWRKY4 and FsMAPK3 in Forsythia suspensa.

Forsythia suspensa is a deciduous shrub that belongs to the family Myrtaceae, and its dried fruits are used as medicine. F. suspensa contains several secondary metabolites, which exert pharmacological effects. One of the main active components is forsythin, which exhibits free radical scavenging, antioxidant, anti-inflammatory, and anti-cancer effects. Mitogen-activated protein kinase (MAPKs) can increase the activity of WRKY family transcription factors in a phosphorylated manner, thereby increasing the content of secondary metabolites. However, the mechanism of interaction between MAPKs and WRKYs in F. suspensa remains unclear. In this study, we cloned the genes of FsWRKY4 and FsMAPK3, and performed a bioinformatics analysis. The expression patterns of FsWRKY4 and FsMAPK3 were analyzed in the different developmental stages of leaf and fruit from F. suspensa using real-time fluorescence quantitative PCR (qRT-PCR). Subcellular localization analysis of FsWRKY4 and FsMAPK3 proteins was performed using a laser scanning confocal microscope. The existence of interactions between FsWRKY4 and FsMPAK3 in vitro was verified by yeast two-hybridization. Results showed that the cDNA of FsWRKY4 (GenBank number: OR566682) and FsMAPK3 (GenBank number: OR566683) were 1587 and 522 bp, respectively. The expression of FsWRKY4 was higher in the leaves than in fruits, and the expression of FsMAPK3 was higher in fruits but lower in leaves. The subcellular localization results indicated that FsWRKY4 was localized in the nucleus and FsMAPK3 in the cytoplasm and nucleus. The prey vector pGADT7-FsWRKY4 and bait vector pGBKT7-FsMAPK3 were constructed and co-transferred into Y2H Glod yeast receptor cells. The results indicated that FsWRKY4 and FsMAPK3 proteins interact with each other in vitro. The preliminary study may provide a basis for more precise elucidation of the synthesis of secondary metabolites in F. suspensa.

Engineered exosomes reprogram Gli1+ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels.

Calcification of autologous pathological vessels and tissue engineering blood vessels (TEBVs) is a thorny problem in clinic. However, there is no effective and noninvasive treatment that is available against the calcification of TEBVs and autologous pathological vessels. Gli1+ cells are progenitors of smooth muscle cells (SMCs) and can differentiate into osteoblast-like cells, leading to vascular calcification. Our results showed that the spatiotemporal distribution of Gli1+ cells in TEBVs was positively correlated with the degree of TEBV calcification. An anticalcification approach was designed consisting of exosomes derived from mesenchymal stem cells delivering lncRNA-ANCR to construct the engineered exosome-Ancr/E7-EXO. The results showed that Ancr/E7-EXO effectively targeted Gli1+ cells, promoting rapid SMC reconstruction and markedly inhibiting Gli1+ cell differentiation into osteoblast-like cells. Moreover, Ancr/E7-EXO significantly inhibited vascular calcification caused by chronic kidney disease. Therefore, Ancr/E7-EXO reprogrammed Gli1+ cells to prevent calcification of vascular graft and autologous pathological vessel, providing unique insights for an effective anticalcification.

[The fenrou zhijian theory in The Inner Canon of Huangdi and the stratified treatment of painful bi syndrome of meridian tendons].

The fenrou zhijian is defined as potential gap between different layers in the three-dimensional network structure formed by the twelve meridian tendons. Various pathological changes of the meridian tendons lead to the adhesion and closure of fenrou zhijian, causing abnormal mechanical conduction of the meridian tendon system, which in turn leads to painful bi syndrome of meridian tendons. As such, restarting the fenrou zhijian is the key to acupuncture treatment for painful bi syndrome of meridian tendons. Under the guidance of musculoskeletal ultrasound, the level and the angle of needle insertion of acupuncture at fenrou zhijian could be accurately controlled, the efficacy of acupuncture is improved.

Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial.

BACKGROUND: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML. METHODS: A phase 2 clinical trial was performed in 10 Chinese hospitals to investigate Ven combined with daunorubicin and cytarabine (DA 2 + 6) in patients with AML. The primary endpoints were overall response rate (ORR), comprising of complete remission (CR), complete remission with incomplete blood cell count recovery (CRi), and partial response (PR). Secondary endpoints included measurable residual disease (MRD) of bone marrow assessed by flow cytometry, overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and the safety of regimens. This study is a currently ongoing trial listed on the Chinese Clinical Trial Registry as ChiCTR2200061524. RESULTS: Overall, 42 patients were enrolled from January 2022 to November 2022; 54.8% (23/42) were male, and the median age was 40 (range, 16-60) years. The ORR after one cycle of induction was 92.9% (95% confidence interval [CI], 91.6-94.1; 39/42) with a composite complete response rate (CR + CRi) 90.5% (95% CI, 89.3-91.6, CR 37/42, CRi 1/42). Moreover, 87.9% (29/33) of the CR patients with undetectable MRD (95% CI, 84.9-90.8). Grade 3 or worse adverse effects included neutropenia (100%), thrombocytopenia (100%), febrile neutropenia (90.5%), and one mortality. The median neutrophil and platelet recovery times were 13 (5-26) and 12 (8-26) days, respectively. Until Jan 30, 2023, the estimated 12-month OS, EFS, and DFS rates were 83.1% (95% CI, 78.8-87.4), 82.7% (95% CI, 79.4-86.1), and 92.0% (95% CI, 89.8-94.3), respectively. CONCLUSION: Ven with DA (2 + 6) is a highly effective and safe induction therapy for adults with newly diagnosed AML. To the best of our knowledge, this induction therapy has the shortest myelosuppressive period but has similar efficacy to previous studies.

Expression Analysis of CoHMGS in Cornus officinalis and Subcellular Localization of the Enzyme It Encodes.

Cornus officinalis is a perennial deciduous tree or shrub. Its mature fruits are extracted and used in Traditional Chinese Medicine, called Shanzhuyu. The characteristic active components of C. officinalis include loganin and morroniside, which belong to iridoid glycosides. 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is a key enzyme in the cytoplasmic mevalonate pathway providing the precursor molecules isopentenyl pyrophosphate and dimethylallyl pyrophosphate for isoprenoid biosynthesis such as sterols, triterpenes, and their derivatives such as iridoid glycosides. Different concentrations of methyl jasmonate (MeJA) and ethephon (ETH) solutions were sprayed on C. officinalis seedlings, and the effect of hormones on CoHMGS gene expression was detected by real-time fluorescence quantitative PCR. The quantitative real-time PCR results showed that 750 mg/L ETH treatment had the most significant induction effect on CoHMGS gene expression. The HPLC analysis of extracts revealed that the treatment could also significantly increase the content of morroniside and loganin in the leaves of C. officinalis. By use of a CoHMGS-green fluorescent protein (GFP) fusion construct for heterologous expression in tobacco, laser scanning confocal microscopy revealed a cytoplasmic localization. This preliminary study of the CoHMGS gene could prepare the ground for more precisely elucidating the synthesis of secondary metabolite in C. officinalis.

Clinical efficacy of electromagnetic field therapy combined with traditional Chinese pain-reducing paste in myofascial pain syndrome.

BACKGROUND: Pulsed electromagnetic field (PEMF) therapy is widely used to treat myofascial pain syndrome (MPS). Damp-clearing and pain-reducing paste (DPP) comprises medical herbs and has been a traditional method of reducing myofascial pain in China for a long time, and it is usually administered with heating. However, the synergistic effect of PEMF therapy on heating-DPP in patients with MPS is unclear. AIM: To investigate the synergistic effect of PEMF therapy plus heating-DPP in lumbar MPS. METHODS: This double-blind, randomized, placebo-controlled trial was conducted on 120 patients with lumbar MPS who were randomly divided into an experimental group (EG, n = 60) and a control group (CG, n = 60). Patients in both groups were treated with heating-DPP combined with PEMF therapy; however, the electromagnetic function of the therapeutic apparatus used in the CG was disabled. Each treatment lasted for 20 min and was applied five times a week for two weeks. The short-form McGill Pain Questionnaire was applied at five time points: pretest, end of the first and second weeks of treatment, and end of the first and fourth week after completing treatment. Visual analog scale (VAS), present pain intensity index (PPI), and pain rating index (PRI; total, affective pain, and sensory pain scores) scores were then analyzed. RESULTS: Compared with the CG, the VAS, PPI and PRI scores (total, affective pain and sensory pain scores) in the EG were significantly lower after treatment and during follow-up. CONCLUSION: PEMF therapy combined with heating-DPP showed better efficacy than heating-DPP alone in reducing the overall intensity of pain and sensory and affective pain.

Comparative Transcriptome Analysis of MeJA Responsive Enzymes Involved in Phillyrin Biosynthesis of Forsythia suspensa.

Forsythia suspensa (Thunb.) has been widely used in traditional medicines in Asia. According to the 2020 edition of Chinese Pharmacopoeia, phillyrin is the main active ingredient in F. suspensa, which is effective in clearing heat, reducing swelling, and dispersing nodules. F. suspensa leaf is a non-toxic substance and it can be used to make a health tea. Here, we combine elicitors and transcriptomics to investigate the inducible biosynthesis of the phillyrin from the F. suspensa. After the fruits and leaves of F. suspensa were treated with different concentrations of methyl jasmonate (MeJA), the content of phillyrin in the fruits reached a peak at 200 µM MeJA for 12 h, but which was decreased in leaves. To analyze the differences in key enzyme genes involved in the phillyrin biosynthesis, we sequenced the transcriptome of F. suspensa leaves and fruits treated with 200 µM MeJA for 12 h. We hypothesized that nine genes related to coniferin synthesis including: F. suspensa UDP-glycosyltransferase (FsUGT); F. suspensa 4-coumarate coenzyme CoA ligase (Fs4CL); and F. suspensa Caffeoyl-CoA O-methyltransferase (FsCCoAOMT) etc. The qRT-PCR analysis of genes related to phillyrin biosynthesis was consistent with RNA-seq analysis. We also investigated the dynamic changes of genes in F. suspensa leaves and fruits at different time points after 200 µM MeJA treatment, which laid the foundation for further study of the molecular mechanisms regulating the biosynthesis of phillyrin.

A Case of Daratumumab-Induced Significant Decrease in Donor-Specific HLA Antibodies and Remission Induction Before Haploidentical Stem Cell Transplantation in a Refractory B-ALL Patient.

OBJECTIVE: To explore the method of eliminating donor-specific anti-HLA antibodies (DSA) in haploidentical stem cell transplantation (haplo-SCT). METHODS: We present a refractory B-cell acute lymphoblastic leukemia (ALL) patient who had strongly positive DSA, but had no human leukocyte antigen-matched donor. Although CD38 expression on leukemia cells was negative, daratumumab combined with etoposide and venetoclax therapy was chosen for her. RESULTS: She achieved a significant decrease in DSA levels and complete remission on the combination therapy with daratumumab. She then received a haplo-SCT from a daughter as a donor and had a successful engraftment of donor stem cell. In haplo-SCT, strongly positive DSA levels, directed against donor HLA antigens, could be significantly reduced by daratumumab therapy before transplantation and successfully bridge subsequent haplo-SCT. CONCLUSION: Although CD38 expression is negative in leukemia cells, refractory B-ALL patients may still benefit from combination therapy with daratumumab. We need further clinical observation.

Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts.

Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.

Design, Synthesis, and Bioactivity of Eighteen Novel 2H-1,4-Benzoxazin-3(4H)-one Containing a Propanolamine Moiety.

To develop a novel skeleton for broad-spectrum pesticides with high-efficiency against tea tree diseases, a series of aniline 2H-1,4-benzoxazin-3(4H)-one derivatives containing a propanolamine structure was synthesized and confirmed by 1 H-NMR, 13 C-NMR, 19 F-NMR, HRMS, and single-crystal diffraction analysis. Bioactivities were evaluated against tobacco mosaic virus (TMV, the model virus), three kinds of bacteria, and five typical plant fungi. Bioassay results showed that compound 2i (EC50 =395.05 µg/mL) had the best curative activity against TMV, 3d (EC50 =45.70 µg/mL) had the best inhibitory activity against Pseudomonas syringae pv. Actinidiae, and 3a (EC50 =13.53 µg/mL) had the best inhibitory activity against Pestalotiopsis trachicarpicola. Scanning electron microscope morphological observation of P. trachicarpicola treated with 0, 100, and 200 µg/mL 3a revealed dried, flattened and folded outer walls of the hyphae at higher concentrations, leading to inhibition of fungal growth. The broad-spectrum bioactivities (against viruses, bacteria and fungi) of this series of target compounds indicate that these 2H-1,4-benzoxazin-3(4H)-one derivatives containing a propanolamine moiety are potential skeletons for developing pesticides with wide-ranging activities against various tea tree diseases.

Genome-wide analysis and functional characterization of CHYR gene family associated with abiotic stress tolerance in bread wheat (Triticum aestivum L.).

BACKGROUND: CHY zinc-finger and RING finger (CHYR) proteins have been functionally characterized in plant growth, development and various stress responses. However, the genome-wide analysis was not performed in wheat. RESULTS: In this study, a total of 18 TaCHYR genes were identified in wheat and classified into three groups. All TaCHYR genes contained CHY-zinc finger, C3H2C3-type RING finger and zinc ribbon domains, and group III members included 1-3 hemerythrin domains in the N-terminus regions. TaCHYR genes in each group shared similar conserved domains distribution. Chromosomal location, synteny and cis-elements analysis of TaCHYRs were also analyzed. Real-time PCR results indicated that most of selected 9 TaCHYR genes exhibited higher expression levels in leaves during wheat seedling stage. All these TaCHYR genes were up-regulated after PEG treatment, and these TaCHYRs exhibited differential expression patterns in response to salt, cold and heat stress in seedling leaves. The growth of yeast cells expressing TaCHYR2.1, TaCHYR9.2 and TaCHYR11.1 were inhibited under salt and dehydration stress. Moreover, gene ontology (GO) annotation, protein interaction and miRNA regulatory network of TaCHYR genes were analyzed. CONCLUSIONS: These results increase our understanding of CHYR genes and provide robust candidate genes for further functional investigations aimed at crop improvement.

Thorax Dynamic Modeling and Biomechanical Analysis of Chest Breathing in Supine Lying Position.

During respiration, the expansion and contraction of the chest and abdomen are coupled with each other, presenting a complex torso movement pattern. A finite element (FE) model of chest breathing based on the HUMOS2 human body model was developed. One-dimensional muscle units with active contraction functions were incorporated into the model based on Hill's active muscle model so as to generate muscle contraction forces that can change over time. The model was validated by comparing it to the surface displacement of the chest and abdomen during respiration. Then, the mechanism of the coupled motion of the chest and abdomen was analyzed. The analyses revealed that since the abdominal wall muscles are connected to the lower edge of the rib cage through tendons, the movement of the rib cage may cause the abdominal wall muscles to be stretched in both horizontal and vertical in a supine position. The anteroposterior and the right-left diameters of the chest will increase at inspiration, while the right-left diameter of the abdomen will decrease even though the anteroposterior diameter of the abdomen increases. The external intercostal muscles at different regions had different effects on the motion of the ribs during respiration. In particular, the external intercostal muscles at the lateral region had a larger effect on pump handle movement than bucket handle movement, and the external intercostal muscles at the dorsal region had a greater influence on bucket handle movement than pump handle movement.

Antagonistic Activity of Fungal Strains against Fusarium Crown Rot.

The crown rot of wheat is a destructive soil-borne pathogen that severely reduces the yield and quality of wheat. This study aimed to screen and identify the antagonistic strains against Fusarium pseudograminearum (Fp), which is the dominant pathogen associated with the crown rot of wheat in China, and evaluate their biosynthetic potential. The antagonistic strains were screened via a dual-culture antagonism assay, and then identified by combining the morphological characteristics and internal transcribed spacer gene sequencing. The polyketide synthases (PKS-I and PKS-II) and non-ribosomal peptide synthetase (NRPS) genes in the antagonistic strains were detected via specific amplification of chromosomal DNA. Eleven out of 157 fungal strains, including six strains with matrix competition and five strains with antibiosis, were obtained. The eleven antagonistic strains belonged to the following four genera: Alternaria, Botryosphaeria, Phoma and Talaromyces. The inhibition rate of six strains with matrix competition was greater than 50%, with B. dothidea S2-22 demonstrating the highest at 80.3%. The width of the inhibition zone of T. trachyspermus R-17 among the five strains with antibiosis was the widest at 11 mm. Among the eleven antagonistic strains, three strains of A. alternata and the strain P. moricola only contained the PKS-II gene, the strain A. tenuissima contained PKS-I and PKS-II genes, three strains of B. dothidea contained PKS-II and NRPS genes, while three strains of T. trachyspermus did not contain any genes. These results demonstrated potential strains for the biocontrol of the crown rot of wheat. In particular, T. trachyspermus R-17 can be investigated further as a promising agent, and the active substances secreted by antagonistic strains may be synthesized by other pathways.

Review on the Vascularization of Organoids and Organoids-on-a-Chip.

The use of human cells for the construction of 3D organ models in vitro based on cell self-assembly and engineering design has recently increased in popularity in the field of biological science. Although the organoids are able to simulate the structures and functions of organs in vitro, the 3D models have difficulty in forming a complex vascular network that can recreate the interaction between tissue and vascular systems. Therefore, organoids are unable to survive, due to the lack of oxygen and nutrients, as well as the accumulation of metabolic waste. Organoids-on-a-chip provides a more controllable and favorable design platform for co-culture of different cells and tissue types in organoid systems, overcoming some of the limitations present in organoid culture. However, the majority of them has vascular networks that are not adequately elaborate to simulate signal communications between bionic microenvironment (e.g., fluid shear force) and multiple organs. Here, we will review the technological progress of the vascularization in organoids and organoids-on-a-chip and the development of intravital 3D and 4D bioprinting as a new way for vascularization, which can aid in further study on tissue or organ development, disease research and regenerative medicine.

Characterization and phytotoxicity of ophiobolins produced by Bipolaris setariae.

The Bipolaris setariae NY1 strain, isolated from a diseased green foxtail plant in Henan Province, China, showed strong pathogenicity towards green foxtail. In order to clarify the role of phytotoxic substances in the fungal pathogenicity, bioassay-directed isolation and bioactivity assays of secondary metabolites produced by the fungal strain were carried out. Five ophiobolins were obtained: 3-anhydro-ophiobolin A, 6-epi-ophiobolin A, 6-epi-ophiobolin B, 3-anhydro-6-epi-ophiobolin B and ophiobolin I. Bioassays on punctured and intact detached leaves of green foxtail indicated that 3-anhydro-ophiobolin A was the most phytotoxic, followed by 6-epi-ophiobolin A. The other three ophiobolins appeared to be inactive against green foxtail. The effects of 3-anhydro-ophiobolin A and 6-epi-ophiobolin A were synergistic. The symptoms on green foxtail caused by 3-anhydro-ophiobolin A or its mixture with 6-epi-ophiobolin A resembled those caused by the fungus. 3-Anhydro-ophiobolin A and 6-epi-ophiobolin A are likely the main pathogenic determinants of B. setariae. 6-epi-Ophiobolin A caused cytotoxicity against five kinds of human cancer cells: human colon adenocarcinoma cells (HCT-8), human liver cancer cells (Bel-7402), human gastric cancer cells (BGC-823), human lung adenocarcinoma cells (A549), and human ovarian adenocarcinoma cells (A2780). The results provide information for the development of herbicides and antitumor potential of the ophiobolin sesterterpenes.

Targeted In Vivo Delivery of NF-κB Decoy Inhibitor Augments Sensitivity of B Cell Lymphoma to Therapy.

Despite recent advances, non-Hodgkin's B cell lymphoma patients often relapse or remain refractory to therapy. Therapeutic resistance is often associated with survival signaling via nuclear factor κB (NF-κB) transcription factor, an attractive but undruggable molecular target. In this study, we describe a bipartite inhibitor comprising a NF-κB-specific decoy DNA tethered to a CpG oligodeoxynucleotide (ODN) targeting Toll-like receptor-9-expressing B cell lymphoma cells. The Bc-NFκBdODN showed efficient uptake by human diffuse large B cell (U2932, OCI-Ly3), Burkitt (RaJi), and mantle cell (Jeko1) lymphomas, respectively. We confirmed that Bc-NFκBdODN inhibited NF-κB nuclear translocation and DNA binding, resulting in CCND2 and MYC downregulation. Bc-NFκBdODN enhanced radiosensitivity of lymphoma cells in vitro. In xenotransplanted human lymphoma, local injections of Bc-NFκBdODN reduced NF-κB activity in whole tumors. When combined with a local 3-Gy dose of radiation, Bc-NFκBdODN effectively arrested OCI-Ly3 lymphoma progression. In immunocompetent mice, intratumoral injections of Bc-NFκBdODN suppressed growth of directly treated and distant A20 lymphomas, as a result of systemic CD8 T cell-dependent immune responses. Finally, systemic administration of Bc-NFκBdODN to mice bearing disseminated A20 lymphoma induced complete regression and extended survival of most of the treated mice. Our results underscore clinical relevance of this strategy as monotherapy and in support of radiation therapy to benefit patients with resistant or relapsed B cell lymphoma.

Characteristics and risk factors for extrauterine growth retardation in very-low-birth-weight infants.

BACKGROUND: To investigate the characteristics and risk factors for extrauterine growth retardation (EUGR) in very-low-birth-weight infants (VLBWIs). METHODS: The medical records of 137 VLBWIs admitted to the neonatal intensive care unit between June 2015 and December 2017 were retrospectively reviewed. The patients were divided into EUGR (n = 92) and non-EUGR (n = 45) groups. This study collected data on demographic and clinical characteristics and analyzed the risk factors for EUGR with multivariate logistic regression. RESULTS: Gestational age (OR = 0.573, P < .01), SGA (OR = 3.887, P = .022), feeding intolerance (OR = 4.632, P = .002), and calories supplied by amino acids at the 7th day (OR = 0.786, P = .006) were high-risk factors for EUGR. CONCLUSION: Feeding intolerance reduction and amino acid nutrition support should be applied to prevent delayed extrauterine growth for VLBWIs.