Steady regime of radiation pressure acceleration with foil thickness adjustable within micrometers under a 10-100 PW laser.

Quasimonoenergetic GeV-scale protons are predicted to be efficiently generated via radiation pressure acceleration (RPA) when the foil thickness is matched with the laser intensity, e.g., L_{mat} of several nm to 100 nm for 10^{19}-10^{22}Wcm^{-2} available in laboratory. However, nonmonoenergetic protons with much lower energies than predicted were usually observed in RPA experiments because of too small foil thickness which cannot support insufficient laser contrast and foil surface roughness. Besides the technical problems, we here find that there is an upper-limit thickness L_{up} derived from the requirement that the laser energy should dominate over the ion source energy in the effective laser-proton interaction zone, and L_{up} is lower than L_{mat} with the intensity below 10^{22}Wcm^{-2}, which causes inefficient or unsteady RPA. As the intensity is enhanced to ≥10^{23}Wcm^{-2} provided by 10-100 PW laser facilities, L_{up} can significantly exceed L_{mat}, and therefore RPA becomes efficient. In this regime, L_{mat} acts as a lower-limit thickness for efficient RPA, so the matching thickness can be extended to a continuous range from L_{mat} to L_{up}; the range can reach micrometers, within which foil thickness is adjustable. This makes RPA steady and meanwhile the above technical problems can be overcome. Particle-in-cell simulation shows that multi-GeV quasimonoenergetic proton beams can be steadily generated and the fluctuation of the energy peaks and the energy conversation efficiency remains stable although the thickness is taken in a larger range with increasing intensity. This work predicts that near future RPA experiments with 10-100 PW facilities will enter a new regime with a large range of usable foil thicknesses that can be adjusted to the interaction conditions for steady acceleration.

Efficacy and Safety of Bilateral Ultrasound-Guided Erector Spinae Plane Block for Postoperative Analgesia in Spine Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: A meta-analysis of randomized controlled trials was conducted to assess efficacy and safety of bilateral ultrasound-guided erector spinae plane block (ESPB) for postoperative analgesia in patients receiving spine surgery. METHODS: PubMed, Embase, and CENTRAL databases were searched by 2 reviewers independently to identify randomized controlled trials evaluating the efficacy of ultrasound-guided ESPB for pain management in patients undergoing spine surgery. For meta-analysis, mean difference (MD) and 95% confidence interval (CI) were selected for continuous data, and risk ratio (RR) and 95% CI were selected for dichotomous variables. RESULTS: A total of 25 randomized controlled trials including 1917 patients (873 in ESPB group and 874 in control group) were eligible for inclusion. At rest, ESPB was associated with significantly lower pain intensity at 0, 2, 4, 6, 8, 12, 24, and 48 hours compared with the control group. During movement, ESPB was associated with significantly lower pain intensity at 0, 4, 6, 8, 12, 24, and 48 hours compared with the control group. Significantly reduced opioid consumption (MD = -6.29, 95% CI [-8.16, 4.41], P < 0.001), prolonged time for first rescue analgesia (MD = 7.51, 95% CI [3.47, 11.54], P < 0.001), fewer patients needing rescue analgesia (RR = 0.34, 95% CI [0.28, 0.43], P < 0.0001), improved patient satisfaction (MD = 1.34, 95% CI [0.88, 1.80], P < 0.001), and shorter length of hospital stay (MD = -0.38, [95% CI -0.50, -0.26], P < 0.001) were demonstrated after use of ESPB. Additionally, ESPB was associated with decreased risks of any adverse event (RR = 0.51, 95% CI [0.43, 0.60], P < 0.001) and postoperative nausea and vomiting events (RR = 0.39, 95% CI [0.31, 0.49], P < 0.001). CONCLUSIONS: Ultrasound-guided ESPB is an effective adjunctive technique with good tolerability for multimodal analgesia in management of pain in patients undergoing spine surgery.

Factors Associated with Re-Displacement after Nonsurgical Treatment of Distal Radius Fractures in Adults: A Retrospective Study.

OBJECTIVE: Closed reduction combined with external fixation is a frequently utilized approach for treating distal radial fractures in adults. Nonetheless, the potential for re-displacement following external fixation remains. Analyzing the factors influencing re-displacement after nonsurgical treatment of distal radial fractures in adults is vital for preventing re-displacement and making prognostic assessments. METHODS: A retrospective analysis was performed on 884 patients who underwent nonsurgical treatment for distal radius fractures in the reduction room of the Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine at Tianjin Hospital, Tianjin, China, between July 2019 and December 2022. Patients were categorized into two groups, namely displaced and nondisplaced, based on radiographic outcomes. Factors affecting fracture re-displacement were examined, including sex, age, side, AO/OTA type, external fixation, and radiographic outcomes at pre-reduction and immediate reduction. Logistic regression analysis was employed to identify the risk factors for fracture re-displacement, and ROC curves were constructed. RESULTS: Among the 884 patients, 563 (63.69%) experienced re-displacement after fracture reduction. There were no statistically significant differences (p > 0.05) between the two groups in terms of gender, external fixation method, and palmar tilt angle at pre-reduction and immediate reduction, while significant differences (p < 0.05) were observed in age, side, AO/OTA type, and radial inclination, radial length, and radiographic outcomes of ulnar variance at pre-reduction and immediate reduction. Multifactorial logistic regression analysis revealed that age (odds ratio [OR] = 1.027, p < 0.001), AO/OTA type (OR = 2.327, p = 0.005), ulnar variance at pre-reduction (OR = 1.142, p = 0.048), and ulnar variance at immediate reduction (OR = 1.685, p < 0.001) were significant factors (p < 0.05) associated with re-displacement following nonoperative treatment of adult distal radius fractures. For patients aged ≥60 years, the amount of missing radiographic outcomes was positively correlated with age. The receiver operating characteristic curve demonstrated that age ≥65.5 years, ulnar variance >3.26 mm at pre-reduction, and ulnar variance >2.055 mm at immediate reduction were high-risk factors for fracture re-displacement. CONCLUSIONS: Nonsurgical treatment of distal radius fractures exhibits a higher rate of re-displacement. Age, AO/OTA type, pre-reduction, and immediate reduction ulnar variance are key factors predicting fracture re-displacement.

Epirubicin-induced Kounis syndrome.

BACKGROUND: Kounis syndrome is an acute coronary syndrome that appears in the setting of anaphylactic reaction or hypersensitivity. Many drugs and environmental exposures have been identified as potential offenders, and diagnosis and treatment can be challenging. CASE PRESENTATION: A 62-year-old man with recurrent bladder cancer underwent an intra-iliac artery epirubicin injection. After the injection, he developed chest pain and a systemic allergic reaction, with electrocardiographic alterations and elevated troponin-I levels. Emergent coronary angiography showed right coronary artery spasm and no stenosis of the other coronary arteries. This reaction was considered compatible with an allergic coronary vasospasm. A diagnosis of Kounis syndrome was made. CONCLUSIONS: Kounis syndrome is common, but a prompt diagnosis is often not possible. This case is the first to suggest that an intraarterial epirubicin injection could potentially be one of its triggers. All physicians should be aware of the pathophysiology of this condition to better recognize it and start appropriate treatment; this will prevent aggravation of the vasospastic cardiac attacks and yield a better outcome.

Late-onset anastomotic leak following sweet esophagectomy: A case report and review of the literature.

RATIONALE: Late-onset anastomotic leak (AL) is an uncommon but potentially lethal complication after esophagectomy. PATIENT CONCERNS: A 74-year-old male patient was readmitted due to chest distress and chills about 3 months after initial esophagectomy for cancer. DIAGNOSES: The previous endoscopic biopsy revealed primary esophageal squamous cell carcinoma, and sweet esophagectomy with gastric conduit reconstruction was therefore performed. The patient developed AL 3 months after the surgery. INTERVENTIONS: Naso-leakage extraluminal drainage tube was utilized because the symptoms of the patient were aggravated 1 month after the chest tube drainage since his second admission for AL. OUTCOMES: Twenty-one days after naso-leakage extraluminal drainage, the computed tomography images showed the healing of the leakage. Then the patient was discharged from the hospital. LESSONS: Late-onset AL should be kept in mind when the patient complained of chest distress and fever during the follow up after esophagectomy. In addition, naso-leakage extraluminal drainage could be considered for the treatment of AL. Further trials for better evidence are warranted.

Extralobar pulmonary sequestration with elevated serum neuron-specific enolase: A case report and review of the literature.

RATIONALE: Pulmonary sequestration (PS) presenting with elevated serum tumor markers is rare, and it might be misdiagnosed as malignancy. PATIENT CONCERNS: A 26-year-old asymptomatic male patient was admitted because the x-ray showed an intrathoracic lesion. Meanwhile, the serum neuron-specific enolase (NSE) was elevated. Three-dimensional computed tomography angiography revealed an isolated feeding vessel arising from the aorta. DIAGNOSES: Extralobular PS was confirmed by computed tomography angiography and postoperative pathological staining. INTERVENTIONS: Two-port thoracoscopic resection of the sequestrated lobe was performed. OUTCOMES: The serum NSE decreased to within the normal range and persisted during the follow up of 10 months. LESSONS: A thorough work-up should be considered for the PS patients presenting with abnormal serum NSE. Detailed knowledge regarding the relationship between NSE and PS necessitates further studies.

Kupffer Cell-Derived TNF-α Triggers the Apoptosis of Hepatic Stellate Cells through TNF-R1/Caspase 8 due to ER Stress.

PURPOSE: To investigate the roles of ER stress in Kupffer cells (KCs) and KC-derived TNF-α in the apoptosis of hepatic stellate cells (HSCs). METHODS: A rat model of liver fibrosis was established. Liver and blood serum samples were collected. Liver function assays, Masson staining, Sirius Red staining, ELISAs, and TUNEL and immunohistochemical staining were performed. Liver function, liver fibrosis, KC phenotype, inflammatory factors, and number of active HSCs were investigated. KCs were isolated, treated with tunicamycin, and then, cocultured with primary hepatic stellate cells. ELISAs, immunofluorescence staining, flow cytometry, and Western blotting were performed. KC phenotype, inflammatory factors, HSC apoptosis, and TNF-R1/caspase 8 pathway activity were examined. RESULT: s. ER stress in KCs reduced the levels of liver function markers, reduced the degree of liver fibrosis, and increased the number of KCs with the M1 phenotype and the expression of TNF-α. The increase in KC-derived TNF-α reduced the number of active HSCs and increased the activity of TNF-R1/caspase 8. Furthermore, ER stress in KCs promoted the polarization of KCs towards the M1 phenotype and increased the expression of TNF-α. The increase in KC-derived TNF-α triggered the apoptosis of HSCs and the activation of TNF-R1/caspase 8 in vitro, which was consistent with the in vivo results. CONCLUSION: ER stress in KCs promotes the polarization of these cells towards the M1 phenotype and increases the expression of TNF-α. Then, the increase in KC-derived TNF-α triggers the apoptosis of HSCs through TNF-R1/caspase 8.

Comparison of bailout and planned rotational atherectomy for severe coronary calcified lesions.

BACKGROUND: To compare outcomes of bailout and planned rotational atherectomy (RA) in the treatment of severe calcified coronary lesions. METHODS: Data of patients treated with RA from 2017 to 2018 at a single-center registry were retrospectively analyzed. All patients were divided into planned RA and bailout RA groups, data between two groups were compared. RESULTS: A total of 190 patients were included in this study, 138 patients received planned RA and 52 patients received bailout RA. Baseline clinical characteristics had no significant differences between groups. The number of implanted stents and total stents length were similar. But the number of balloon (1.6 ± 0.8 vs. 2.7 ± 1.3, P < 0.001), procedure time (83.5 ± 26.2 vs. 100.8 ± 36.4 min, P = 0.007), fluoroscopy volume (941 ± 482 vs. 1227 ± 872 mGy, P = 0.012] and contrast amount (237 ± 62 vs. 275 ± 90 ml, P = 0.003) were all lower in planned RA group. Planned RA had a higher procedural success rate (99.3% vs. 92.3%, P = 0.007) and a lower complication incidence (4.3% vs. 17.3%, P = 0.009). But the primary outcomes at 3 years (9.2 and 16.6%, log rank p = 0.24) had no difference between groups. CONCLUSIONS: For severe coronary artery calcification, although planned RA did not improved the long term prognosis compared with bailout RA, but it can improve the immediate procedural success rate, reduce the incidence of complications, the procedure time and the volume of contrast.

First-line albumin-bound paclitaxel/carboplatin plus apatinib in advanced pulmonary sarcomatoid carcinoma: A case series and review of the literature.

RATIONALE: Pulmonary sarcomatoid carcinoma (PSC) is an uncommon type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to the conventional chemoradiotherapy. To date, the optimal treatment for PSC has not been elucidated. PATIENT CONCERNS: Three male patients including a 69-year-old smoker (Case 1), a 45-year-old non-smoker (Case 2), and a 69-year-old smoker (Case 3) were admitted because of cough, back pain, and loss of body weight respectively. DIAGNOSES: Radiographical examinations in these patients showed bulky intrathoracic lesions, which were pathologically diagnosed as PSC staging III-IV by computed tomography-guided percutaneous biopsy and endoscopy. INTERVENTIONS: Immunotherapy was not covered by their health insurance and they refused immune checkpoint inhibitors for financial reasons. In addition, a radical resection was not appropriate due to the advanced staging of these lesions. Therefore, first-line albumin-bound paclitaxel (nab-paclitaxel, 260 mg/m of the body surface area) and carboplatin (area under curve 5) combined with oral apatinib (425 mg, daily) were administered empirically. OUTCOMES: Two patients achieved a partial response and the other case showed stable disease lasting for more than 6 months. However, 1 of them indicated progression on the 7-month follow up. LESSONS: Nab-paclitaxel/carboplatin plus apatinib showed limited short-term efficacy in advanced, unresectable PSC. The rapid resistance of PSC to the current therapeutic regimen necessitates further researches, as more effective agents are urgently needed.

[Clinical and Pathological Characteristics of Related-Renal Damage in Patients with POEMS Syndrome].

OBJECTIVE: To investigated the clinical and pathological characteristics of related-renal damage in patients with POEMS syndrome. METHODS: Five patients diagnosed as POEMS syndrome in our hospital were selected. Their clinical manifestation, pathological characteristics of kidney and laboratory examination were analyzed retrospectively. Among the 5 patients, three males and two females with a median age of 50 years old. The mean interval before diagnosis was 13.0±7.2 months. RESULTS: All the patients showed neuropathy, endocrinopathy, monoclonal plasma cell-proliferative disorder, skin changes and extravascular volume overload, in which 4 patients showed organomegaly. Proteinuria was found in 5 patients, and microhematuria was found in 4 patients. Moreover, 4 patients showed an elevated blood urea, while 2 patients showed creatinine elevation. 1 patient at chronic kidney disease (CKD)-G1 stage, 2 patients at CKD-G2 stage, and 1 patient at CKD-G3b stage, moreover, 1 patient at CKD-G5 stage. Endothelial injury and mesangial lesion were the main characteristics of renal pathology. 3 patients were pathologically diagnosed as thrombotic microangiopathy kidney damage, while 2 patients as light chain amyloidosis. CONCLUSION: POEMS syndrome is a multi-systemic disease with complex clinical manifestations. 5 patients had different degrees of renal insufficiency. Endothelial injury and mesangial lesion are the main features of renal pathology.

[Comparision of Mutational Spectrum between Elderly and Young Adults with Acute Myeloid Leukemia Based on Next Generation Sequencing].

OBJECTIVE: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS). METHODS: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared. RESULTS: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively. CONCLUSION: The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

[Analysis of Clinical Characteristics and Therapeutic Efficacy of Patients with Adult Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the clinical characteristics and therapeutic efficacy of patient with adult acute lymphoblastic leukemia(ALL). METHODS: Seventy-seven ALL patients diagnosed in the first affiliated hospital of Zhengzhou University from 2018 to 2019 were selected. The immunotyping, fusion gene and gene mutation were detected by flow cytometry, real-time quantitative polymerase chain reaction (RT-PCR) and next generation sequencing (NGS). RESULTS: Among 77 patients with ALL, 66 were B-ALL, 9 were T-ALL. CD7 and cCD3 were the most valuable for the diagnosis of T-ALL, CD19 and cCD79a were the most valuable for the diagnosis of B-ALL, and CD58, CD123 were highly expressed in B-ALL. Three fusion genes: BCR-ABL (20.8%), MLL-AF4 (5.19%) and E2A-PBX1 (2.60%) were detected by RT-PCR and 10 mutant genes were detected by NGS (the total detection rate was 33.47%). The highest mutation rates were IL-7R (6 cases), NOTCH1 (6 cases), TP53 (5 cases) and FLT-3 (4 cases). Patients with IL-7R, NOTCH1 and TP53 mutations showed poor response to induction chemotherapy. CONCLUSION: The CD123, IL-7R, NOTCH1 and TP53 may be risk factors for prognosis, however, the increase of case number and prolonging of follow-up time are needed to further confirm.

Screening of Biomarkers Related to Ovarian Maturation and Spawning in Blunt Snout Bream (Megalobrama amblycephala) Based on Metabolomics and Transcriptomics.

In fish breeding practices, gamete maturity of females is vital to reproductive success. For some species, it is possible to estimate the female maturation status based on abdomen observation, but quite difficult for some species which mature at big size. To screen out the potential biomarker in fish blood relating to female maturation, we employed the approach integrating the UPLC-MS/MS and RNA-seq techniques to investigate the metabolites and genes reflecting the sexual maturation and spawning of female blunt snout bream Megalobrama amblycephala. The study included four groups, 1-year-old immature female individuals, 2-year-old immature female individuals, 2-year-old sexually mature female individuals, and 2-year-old sexually mature female individuals after 24 h of successful spawning. The upregulated metabolites in mature females were involved in "steroid hormone biosynthesis," "metabolic pathways," "glycerophospholipid metabolism," etc. compared with those of immature individuals. As the key intermediate of steroid hormone biosynthesis, 17α-hydroxypregnenolone exhibited the highest level in 2-year-old mature females than in the immature females. Meanwhile, the metabolites (i.e., dodecanoic acid and myristic acid) participating in fatty acid synthesis exhibited much lower levels in the females after spawning than those before spawning. In addition to the metabolites, the genes involved in ovarian steroidogenesis were significantly upregulated in the 2-year-old immature females compared to the 1-year-old immature females, indicating that the ovarian steroidogenesis plays important roles in ovarian development of M. amblycephala at the early stages. The significant upregulation of genes (i.e., itpr1, camk2, and mekk2) involved in the "GnRH signaling pathway" was observed in the mature females compared with the immature females, which indicated that the estrogen levels increased after female maturation in M. amblycephala. Moreover, many genes (e.g., gck, creb1, tf2-9, ryr2, asgr1, and creb1) regulating insulin secretion and thyroid hormone synthesis were significantly downregulated after female spawning. The dynamics of gene expression and metabolites observed in this study provide novel cues for guiding fish practical artificial reproduction.

Dietary betaine reduces liver lipid accumulation via improvement of bile acid and trimethylamine-N-oxide metabolism in blunt-snout bream.

Dietary betaine supplementation notably ameliorated fatty liver disease caused by high dietary carbohydrate. We hypothesised that the mechanism behind this is the alteration of bile acid and trimethylamine-N-oxide (TMAO) metabolism. We further explored this mechanism by supplementing betaine (1%) to the diet of a farmed fish Megalobrama amblycephala. Four diet groups were designed: control (CD, 27.11% carbohydrates), high-carbohydrate (HCD, 36.75% carbohydrates), long-term betaine (HCB, 35.64% carbohydrates; 16 weeks) and short-term betaine (HC4B; 12 weeks HCD + 4 weeks HCB) diets. We analysed the histology of the liver (hematoxylin and eosin staining), the metabolites related to TMAO in plasma (high-performance liquid chromatography-tandem mass spectrometry), the expression of the relative gene in the liver and gut microbiota (qPCR), and the composition of gut microbiota (terminal restriction fragment length polymorphism). HCD elevated lipid accumulation in the liver and decreased the gene expression of bile acid transport, trimethylamine (TMA) formation and the diversity of gut microbiota compared to CD. HCB reversed these patterns, and elevated the gene expression of bile acid receptors and decreased the total cholesterol and TMAO concentration (all compared to HCD). HCD and HCB both increased the gene expression of bile acid synthesis (all p < 0.05). In conclusion, we hypothesise that HCB decreased liver lipid accumulation caused by a high-carbohydrate diet through improvement of the gut microbial community (the diversity of gut microbiota), TMA formation (the expression of associated microbial genes and bacterial taxa), TMAO metabolism (the formation of TMAO) and bile acid metabolism (the gene expression of the synthesis and transport of bile acids and their receptors). HC4B produced intermediate effects of those between HCD and HCB.

Isolation and expression of four Megalobrama amblycephala toll-like receptor genes in response to a bacterial infection.

Toll-like receptors (TLRs) are a category of pattern recognition receptors (PRRs), which recognize pathogen associated molecular patterns (PAMPs) and participate in the immune responses. We identified tlr5a, tlr5b, tlr9 and tlr21 from the genome of blunt snout bream (Megalobrama amblycephala). All four tlrs were constitutively expressed in all examined tissues. After an immune bacterial challenge with Aeromonas hydrophila, their expressionwas up-regulated in lymphoid organs and tissues. Recombinant eukaryotic plasmid pEGFP-N1 was transfected into the common carp (Cyprinus carpio) EPC (epithelioma papulosum cyprini) cells for the purpose of subcellular localization. pcDNA3.1(+) recombinant eukaryotic plasmid was used to investigate the effects of overexpression of tlrs on the expression of downstream interferon-associated immune factors. The four Tlrs were distributed in the cytoplasm of transfected cells and appeared as filamentous or reticular. The expression of irf3, irf7, isg15, mx1, pkr and viperin at 0, 6, 12, 18, 24, 36, 48 and 72 h post-transfection in transfected EPC cells was quantified by qPCR. Overexpression of tlrs upregulated the expression of viperin, isg15, irf3, irf7, mx1 and pkr (in that order of magnitude). We also cloned the following promoters of irfs: Irf1-p, irf2-p, irf6-p, irf7-p, irf8-p and irf9-p. Results of the dual luciferase reporter assay suggested that tlr5a, tlr5b and tlr9 enhanced the activities of irf7-p, while tlr5b enhanced the activities of irf1-p and irf7-p. This suggests that they all play a role in the innate immunity. The experiments also indicated that TLRs activate irf3 or irf7 signaling to induce IFN secretion and subsequent upregulation of IFN-stimulated genes. These results indicate that tlrs and irfs play an important immune role in response to A. hydrophila infection in blunt snout bream, and pave the way for further studies of immune mechanisms mediated by TLRs in fish.

Zebrafish miR-462-731 regulates hematopoietic specification and pu.1-dependent primitive myelopoiesis.

MicroRNAs (miRNAs) play significant roles in both embryonic hematopoiesis and hematological malignancy. Zebrafish miR-462-731 cluster is orthologous of miR-191-425 in human which regulates proliferation and tumorigenesis. In our previous work, miR-462-731 was found highly and ubiquitously expressed during early embryogenesis. In this study, by loss-of-function analysis (morpholino knockdown combined with CRISRP/Cas9 knockout) and mRNA profiling, we suggest that miR-462-731 is required for normal embryonic development by regulating cell survival. We found that loss of miR-462/miR-731 caused a remarkable decrease in the number of erythroid cells as well as an ectopic myeloid cell expansion at 48 hpf, suggesting a skewing of myeloid-erythroid lineage differentiation. Mechanistically, miR-462-731 provides an instructive input for pu.1-dependent primitive myelopoiesis through regulating etsrp/scl signaling combined with a novel pu.1/miR-462-731 feedback loop. On the other hand, morpholino (MO) knockdown of miR-462/miR-731 resulted in an expansion of posterior blood islands at 24 hpf, which is a mild ventralization phenotype resulted from elevation of BMP signaling. Rescue experiments with both BMP type I receptor inhibitor dorsomorphin and alk8 MO indicate that miR-462-731 acts upstream of alk8 within the BMP/Smad signaling pathway and functions as a novel endogenous BMP antagonist. Besides, an impairment of angiogenesis was observed in miR-462/miR-731 morphants. The specification of arteries and veins was also perturbed, as characterized by the irregular patterning of efnb2a and flt4 expression. Our study unveils a previously unrecognized role of miR-462-731 in BMP/Smad signaling mediated hematopoietic specification of mesodermal progenitors and demonstrates a miR-462-731 mediated regulatory mechanism driving primitive myelopoiesis in the ALPM. We also show a requirement for miR-462-731 in regulating arterial-venous specification and definitive hematopoietic stem cell (HSC) production. The current findings might provide further insights into the molecular mechanistic basis of miRNA regulation of embryonic hematopoiesis and hematological malignancy.

Collimated ultrabright gamma rays from electron wiggling along a petawatt laser-irradiated wire in the QED regime.

Even though high-quality X- and gamma rays with photon energy below mega-electron volt (MeV) are available from large-scale X-ray free electron lasers and synchrotron radiation facilities, it remains a great challenge to generate bright gamma rays over 10 MeV. Recently, gamma rays with energies up to the MeV level were observed in Compton scattering experiments based on laser wakefield accelerators, but the yield efficiency was as low as [Formula: see text], owing to low charge of the electron beam. Here, we propose a scheme to efficiently generate gamma rays of hundreds of MeV from submicrometer wires irradiated by petawatt lasers, where electron accelerating and wiggling are achieved simultaneously. The wiggling is caused by the quasistatic electric and magnetic fields induced around the wire surface, and these are so high that even quantum electrodynamics (QED) effects become significant for gamma-ray generation, although the driving lasers are only at the petawatt level. Our full 3D simulations show that directional, ultrabright gamma rays are generated, containing [Formula: see text] photons between 5 and 500 MeV within a 10-fs duration. The brilliance, up to [Formula: see text] photons [Formula: see text] per 0.1% bandwidth at an average photon energy of 20 MeV, is second only to X-ray free electron lasers, while the photon energy is 3 orders of magnitude higher than the latter. In addition, the gamma ray yield efficiency approaches 10%-that is, 5 orders of magnitude higher than the Compton scattering based on laser wakefield accelerators. Such high-energy, ultrabright, femtosecond-duration gamma rays may find applications in nuclear photonics, radiotherapy, and laboratory astrophysics.

[Long Non Coding RNA RP11-69I8.3 Expression in Acute Leukemia and Its Cinical Significance].

OBJECTIVE: To investigate the expression of long non coding RNA RP11-69I8.3 in acute leukemia and its clinical significance. METHODS: lncRNA RP11-69I8.3 expression was detected by RT-PCR in bone marrow samples from 17 healthy controls, 32 newly diagnosed AML patients and 32 newly diagnosed ALL patients, and 25 ALL patients of complete remission after chemotherapy. Meanwhile, the clinical data were collected and the relation of lncRNA RP11-6918.3 expression with the clinical characteristics was analyzed. RESULTS: Compared with the control group, there was no significant difference in the expression of lncRNA RP11-69I8.3 in AML group(P>0.05). lncRNA RP11-69I8.3 lowly expressed in untreated ALL group(P=0.001). Compared with the de novo ALL group, lncRNA RP11-69I8.3 was highly expressed in complete remission ALL group (P<0.013). In 32 de novo ALL patients,the expression of lncRNA RP11-69I8.3 in children was significantly lower than that in adult(P=0.017). There was no correlation of the expression of lncRNA RP11-69I8.3 with the sex, WBC count, HB level, Plt count, LDH level, T or B type, ratio of bone marrow blast cell, BCR/ABL and WT1 fusion gene expression, chromosome karyotype, extramedullary infiltration, whether complete remission after one chemotherapy, whether relapse. In 26 B-ALL patients, there was no correlation between lncRNA RP11-69I8.3 and the immunophenotype. CONCLUSION: The expression of lncRNA RP11-69I8.3 in the untreated AML is not significantly different from the control group. lncRNA RP11-69I8.3 is low expressed in ALL group, highly expressed in ALL group with complete remission. In untreated ALL, the expression of lncRNA RP11-69I8.3 in children is significantly lower than that in adult. In B-ALL patients, the lncRNA RP11-69I8.3 is not relevant with the immunophenotype.

[Expression of Long-Chain Non-coding RNA RP11-87C12.5 in Acute Lymphocytic Leukemia and Its Cinical Significance].

OBJECTIVE: To investigate the expression of long-chain non-coding RNA RP11-87C12.5 in acute lymphocytic leukemia and its clinical significance. METHODS: LncRNA RP11-87C12.5 expression was detected by RT-PCR in bone marrow samples from 17 control group, 33 newly diagnosed ALL patients and 26 complete remission ALL patients after chemotherapy, at the same time the clinical data were collected and the clinical significance of IncRNA RP11-87C12.5 expression was analyzed. RESULTS: Compared with control group, lncRNA RP11-87C12.5 expression increased in newly diagnosed ALL group (P=0.021); compared with newly diagnosed ALL group, IncRNA RP11-87C12.5 expression decreased in complete remission ALL group (P=0.039). lncRNA RP11-87C12.5 expression in newly diagnosed ALL group did not relate with sex, age, T or B type, WBC count, Hb level, Plt count, LDH level, bone marrow blast ratio, BCR/ABL fusion gene expression, chomosome karyotypes, WT1 gene, extrameanllary infiltration or no,complete remission or no after one chemotherapy and relapse or no. In 27 cases of ALL, IncRNA RP11-87C12.5 expression significantly increased in cCD79a low expression group, compared with cCD79a high expression group (P=0.004). IncRNA RP11-87C12.5 expression did not relate with other CD molecules of immunoclassification. CONCLUSION: The expression of LncRNA RP11-87C12.5 is high in newly diagnosed ALL group and low in complete remission ALL group. In B-ALL, the expression of IncRNA RP11-87C12.5 significantly enhances in cCD79a low expression group. In newly diagnosed ALL group, compared with low expression group, lncRNA RP11-87C12.5 high expression group have higer remission rate and relapse rate, but the difference was not statistically significant.