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Abstract Background Fetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts. Case presentation We performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal. Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

Abstract Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources. However, the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater environment. Understanding the characteristics and genesis of groundwater salinization is crucial for preventing its deterioration and ensuring sustainable utilization. In this study, a comprehensive approach combining the ion ratio method, mineral saturation index method and multivariate statistical analysis was employed to investigate the hydrochemical characteristics and main controlling factors in the study area. The findings reveal that: (1) Groundwater samples in study area exhibit a neutral to slightly alkaline pH. The predominant chemical types of unconfined water are HCO3-Ca·Na, HCO3·Cl-Na·Ca and HCO3·SO4-Ca·Na, while confined water mainly exhibits Cl·HCO3-Na and Cl-Na types. (2) Salinity coefficients indicate an increase in salinity from unconfined to confined water. TDS, Na+ and Cl– concentrations show an increasing trend from mountainous to coastal areas in unconfined water, while confined water displays variability in TDS, Na+ and Cl– concentrations. (3) Groundwater salinity is mainly influenced by water-rock interactions, including the dissolution of halite and gypsum, cation exchange, and seawater intrusion etc. Additionally, human activities and carbonate dissolution contribute to salinity in unconfined water. Seawater intrusion is identified as the primary factor leading to higher salinity in confined water compared to unconfined water, with increasing cation exchange and seawater interaction observed from unconfined to confined water.

IntroductionHistomonosis, a protozoan disease caused by Histomonas meleagridis, poses a significant economic burden on domestic poultry in China. To reduce the losses caused by this disease in chickens, an attenuated vaccine was developed by exploiting the diminished virulence of H. meleagridis through successive in vitro passages.MethodsFour experiments were conducted to evaluate the viability of attenuated H. meleagridis as a potential vaccine candidate. Experiment 1 evaluated the route of infection (oral vs. intracloacal) and dose (5 × 104, 1 × 105, and 2 × 105H. meleagridis/chicken) using the virulent strain H. meleagridis JSYZ-D10. Experiment 2 evaluated the attenuated effect of the H. meleagridis JSYZ-D168 strain (infection dose: 2 × 105H. meleagridis/chicken). Experiment 3 evaluated the immunoprotective effect of different immunization doses (5 × 104, 1 × 105, and 2 × 105H. meleagridis/chicken). Experiment 4 evaluated the immunoprotective effect of different immunization schedules (immunization at 3 days of age; immunization at 14 days of age; two immunizations, one at 3 days of age and one at 14 days of age; immunization and infection dose: 2 × 105H. meleagridis/chicken).ResultsThe results showed that the intracloacal route of infection was more effective and stable compared to the oral route. The pathogenicity of the JSYZ-D168 H. meleagridis strain was significantly reduced compared to the original virulent strain. Chickens vaccinated by intracloacal immunization at a dose of 2 × 105H. meleagridis/chicken on day 14 provided effective protection against a virulent strain challenge, significantly resulting in increased body weight and reduced lesions in the cecum and liver within 28 days post-immunization (p

AIM: To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment (RRD) using a novel foldable capsular buckle (FCB). METHODS: This was a series of case observation studies. Eighteen patients (18 eyes) who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included. The procedure was similar to conventional scleral buckling, while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad, external indentation instead of the silicone buckle. The retinal reattachment rate, best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive dioptre and astigmatism degree, and complications were evaluated and recorded. RESULTS: There were 7 males and 11 females aged 19-58y. The average time course of RRD was 12d, ranging from 7-20d. The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes, with macula-off detachments in 12 eyes. The patients were followed-up for at least 6mo. The final retinal reattachment rate was 100%. The BCVA was significantly improved compared with the baseline (P0.05). Three patients had transiently high IOPs within one week after surgery. Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed. CONCLUSION: The success rate of FCB scleral buckling for RRD is satisfactory. This procedure can be expected to be applied in new, uncomplicated cases of RRD.

Glaucoma is a chronic optic neuropathy that affects the retinal ganglion cells, characterized by optic disc atrophy, visual field defects, and visual acuity loss. Since glaucoma is a chronic disease, long-term use of topical intraocular pressure-lowering medications often leads to ocular surface diseases, thus reducing medication adherence and ultimately affecting treatment efficacy. Currently, topical intraocular pressure-lowering medications include prostaglandin derivatives, β-adrenergic blockers, α-adrenergic agonists, topical carbonic anhydrase inhibitors, and cholinergic drugs. This article provides a comprehensive review of the effects and related mechanisms of these five antiglaucoma medications on the ocular surface of glaucoma patients and offers preventative measures for the protection of ocular surface in glaucoma patients.

AIM: To compare the clinical efficacy and safety of ultrasonic cycloplasty (UCP) vs Ahmed glaucoma drainage valve implantation (ADV) in addition to intravitreal anti-vascular endothelial growth factor (VEGF) for treatment of fundus disease-related neovascular glaucoma (NVG). METHODS: A total of 43 patients (45 eyes) with NVG secondary to fundus diseases underwent anti-VEGF combined with UCP or ADV from August 2020 to March 2022 were enrolled in this retrospective cohort study. Of them, 14 patients (15 eyes) were treated with both UCP and anti-VEGF as the UCP group and 29 patients (30 eyes) treated with both ADV and anti-VEGF as the ADV group. The success of the treatment was defined as intraocular pressure (IOP) between 11-20 mm Hg with or without using IOP-lowering drugs. IOP measurement, IOP lowering drugs at baseline and follow-ups period and complications were recorded. RESULTS: The average age was 63.03±9.95 and 52.27±12.89y in ADV and UCP groups, respectively (P=1.947). The fundus pathology included proliferative diabetic retinopathy in 42 eyes and retinal vein occlusion in 3 eyes. All eyes in both groups achieved successful treatment at 3mo. While the success rate was 90.0% (27/30) in the ADV group and 86.7% (13/15) in the UCP group at the last follow-up of 6mo (P>0.05). IOP was significantly lower with reduction of drug use than the baseline in both groups (both P

Abstract We study the quantum coherence in de Sitter space for the bipartite system of Alice and Bob who initially share an entangled state between the two modes of a free massive scalar field. It is shown that the space-curvature effect can produce both local coherence and correlated coherence, leading to the increase of the total coherence of the bipartite system. These results are sharp different from the Unruh effect or Hawking effect, which, in the single mode approximation, cannot produce local coherence and at the same time destroy correlated coherence, leading to the decrease of the total coherence of the bipartite systems. Interestingly, we find that quantum coherence has the opposite behavior compared with the quantum correlation in de Sitter space. We also find that quantum coherence is most severely affected by the curvature effect of de Sitter space for the cases of conformal invariance and masslessness. Our result reveals the difference between the curvature effect in the de Sitter space and the Unruh effect in Rindler spacetime or the Hawking effect in black hole spacetime on quantum coherence.

Epigenetics focuses on DNA methylation, histone modification, chromatin remodeling, noncoding RNAs, and other gene regulation mechanisms beyond the DNA sequence. In the past decade, epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels. The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated. The diabetic condition facilitates epigenetic changes and influences target gene expression. In this review, we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.

AIM: Meta-analysis was performed to systematically evaluate the macular vessel density(VD)and foveal avascular zone(FAZ)areas in patients with no diabetic retinopathy(NDR)by using optical coherence tomography angiography(OCTA). This study aimed to investigate the microcirculatory characteristics of the retina in the early stage of diabetes.METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched for publications from 1 January, 2011 to 5 January, 2021 on OCTA analysis of VD in different regions of the macular area in diabetic patients with NDR. Compare the differences in the superficial parafoveal VD(spafVD), superficial perifoveal VD(spefVD), deep parafoveal VD(dpafVD), deep perifoveal vessel density(dpefVD), superficial FAZ area and best corrected visual acuity(BCVA)between NDR group and the normal control group(healthy population matched for the age at the same time and gender with patients in the NDR group).RESULTS: Thirteen publications with a total of 1 227 eyes(558 eyes in normal control group and 669 eyes in NDR group)were included in the study. Meta-analysis showed that compared with the control group, NDR group displayed a significant decrease in spafVD(MD=-1.90, 95%CI: -2.43--1.37, P

Abstract Background Histomonas meleagridis is an anaerobic, intercellular parasite, which infects gallinaceous birds such as turkeys and chickens. In recent years, the reemergence of Histomoniasis has caused serious economic losses as drugs to treat the disease have been banned. At present, H. meleagridis research focuses on virulence, gene expression analysis, and the innate immunity of the host. However, there are no studies on the differentially expressed miRNAs (DEMs) associated with the host inflammatory and immune responses induced by H. meleagridis. In this research, high-throughput sequencing was used to analyze the expression profile of cecum miRNA at 10 and 15 days post-infection (DPI) in chickens infected with Chinese JSYZ-F strain H. meleagridis. Results Compared with the controls, 94 and 127 DEMs were found in cecum of infected chickens at 10 DPI (CE vs CC) and 15 DPI (CEH vs CCH), respectively, of which 60 DEMs were shared at two-time points. Gene Ontology (GO) functional enrichment analysis of the target genes of DEMs indicated that 881 and 1027 GO terms were significantly enriched at 10 and 15 DPI, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG, www.kegg.jp/kegg/kegg1.html ) pathway enrichment analysis of the target genes of DEMs demonstrated that 5 and 3 KEGG pathways were significantly enriched at 10 and 15 DPI, respectively. For previous uses, the Kanehisa laboratory have happily provided permission. The integrated analysis of miRNA–gene network revealed that the DEMs played important roles in the host inflammatory and immune responses to H. meleagridis infection by dynamically regulating expression levels of inflammation and immune-related cytokines. Conclusion This article not only suggested that host miRNA expression was dynamically altered by H. meleagridis and host but also revealed differences in the regulation of T cell involved in host responses to different times H. meleagridis infection.

IntroductionHistomonas meleagridis can cause histomonosis in poultry. Due to the prohibition of effective drugs, the prevention and treatment of the disease requires new strategies. Questions about its pathogenic mechanisms and virulence factors remain puzzling.MethodsTo address these issues, a tandem mass tag (TMT) comparative proteomic analysis of a virulent strain and its attenuated strain of Chinese chicken-origin was performed.ResultsA total of 3,494 proteins were identified in the experiment, of which 745 proteins were differentially expressed (fold change ≥1.2 or ≤0.83 and p < 0.05), with 192 up-regulated proteins and 553 down-regulated proteins in the virulent strain relative to the attenuated strain.DiscussionSurface protein BspA like, digestive cysteine proteinase, actin, and GH family 25 lysozyme were noted among the proteins up regulated in virulent strains, and these several proteins may be directly related to the pathogenic capacity of the histomonad. Ferredoxin, 60S ribosomal protein L6, 40S ribosomal protein S3, and NADP-dependent malic enzyme which associated with biosynthesis and metabolism were also noted, which have the potential to be new drug targets. The up-regulation of alpha-amylase, ras-like protein 1, ras-like protein 2, and involucrin in attenuated strains helps to understand how it is adapted to the long-term in vitro culture environment. The above results provide some candidate protein-coding genes for further functional verification, which will help to understand the molecular mechanism of pathogenicity and attenuation of H. meleagridis more comprehensively.

Apomixis is the asexual reproduction through seeds that leads to the production of genetically uniform progeny. It has become an important tool in plant breeding because it facilitates the retention of genotypes with desirable traits and allows seeds to be obtained directly from mother plants. Apomixis is rare in most economically important crops, but it occurs in some Malus species. Here, the apomictic characteristics of Malus were examined using four apomictic and two sexually reproducing Malus plants. Results from transcriptome analysis showed that plant hormone signal transduction was the main factor affecting apomictic reproductive development. Four of the apomictic Malus plants examined were triploid, and pollen was either absent or present in very low densities in the stamen. Variation in the presence of pollen was associated with variation in the apomictic percentage; specifically, pollen was absent in the stamens of tea crabapple plants with the highest apomictic percentage. Furthermore, pollen mother cells failed to progress normally into meiosis and pollen mitosis, a trait mostly observed in apomictic Malus plants. The expression levels of meiosis-related genes were upregulated in apomictic plants. Our findings indicate that our simple method of detecting pollen abortion could be used to identify apple plants that are capable of apomictic reproduction.

Locomotion in mollusc Aplysia is implemented by a pedal rolling wave, a type of axial locomotion. Well-studied examples of axial locomotion (pedal waves in Drosophila larvae and body waves in leech, lamprey, and fish) are generated in a segmented nervous system via activation of multiple coupled central pattern generators (CPGs). Pedal waves in molluscs, however, are generated by a single pedal ganglion, and it is unknown whether there are single or multiple CPGs that generate rhythmic activity and phase shifts between different body parts. During locomotion in intact Aplysia, bursting activity in the parapedal commissural nerve (PPCN) was found to occur during tail contraction. A cluster of 20 to 30 P1 root neurons (P1Ns) on the ventral surface of the pedal ganglion, active during the pedal wave, were identified. Computational cluster analysis revealed that there are 2 phases to the motor program: phase I (centered around 168°) and phase II (centered around 357°). PPCN activity occurs during phase II. The majority of P1Ns are motoneurons. Coactive P1Ns tend to be electrically coupled. Two classes of pedal interneurons (PIs) were characterized. Class 1 (PI1 and PI2) is active during phase I. Their axons make a loop within the pedal ganglion and contribute to locomotor pattern generation. They are electrically coupled to P1Ns that fire during phase I. Class 2 (PI3) is active during phase II and innervates the contralateral pedal ganglion. PI3 may contribute to bilateral coordination. Overall, our findings support the idea that Aplysia pedal waves are generated by a single CPG.

Diabetic retinopathy(DR)is the most common complication of diabetes mellitus and remains the leading cause of blindness in working-age population. DR affects almost all the retinal cells, leading to the disruption and dysfunction of neurovascular unit and the neural-glial network. Erythropoietin(EPO), a glycoprotein hormone, plays a pivotal role in neuroprotection, neurotrophy, anti-inflammation, anti-apoptosis and anti-oxidation etc., in various central nervous system diseases. This review discussed the protective effect of EPO in DR so as to provide new options for DR treatment.

Abstract Background Celastrol (cel) was one of the earliest isolated and identified chemical constituents of Tripterygium wilfordii Hook. f. Based on a cel probe (cel-p) that maintained the bioactivity of the parent compound, the targets of cel in cerebral ischemia–reperfusion (I/R) injury were comprehensively analyzed by a quantitative chemical proteomics method. Methods We constructed an oxygen–glucose deprivation (OGD) model in primary rat cortical neurons and a middle cerebral artery occlusion (MCAO) model in adult rats to detect the direct binding targets of cel in cerebral I/R. By combining various experimental methods, including tandem mass tag (TMT) labeling, mass spectrometry, and cellular thermal shift assay (CETSA), we revealed the targets to which cel directly bound to exert neuroprotective effects. Results We found that cel inhibited the proinflammatory activity of high mobility group protein 1 (HMGB1) by directly binding to it and then blocking the binding of HMGB1 to its inflammatory receptors in the microenvironment of ischemia and hypoxia. In addition, cel rescued neurons from OGD injury in vitro and decreased cerebral infarction in vivo by targeting HSP70 and NF-κB p65. Conclusion Cel exhibited neuroprotective and anti-inflammatory effects by targeting HSP70 and NF-κB p65 and directly binding to HMGB1 in cerebral I/R injury.

Varicella outbreaks were mainly reported in developed regions with high vaccine coverage, but not in undeveloped areas. It is still not clear that whether the published data of varicella epidemiology could reflect the reality in China or not. In 2019, 657 subjects from People’s Hospital of Chongqing Youyang County were included. Anti-varicella-zoster virus (VZV) IgG antibodies were determined by ELISA. The anti-VZV IgG levels were categorized as positive when values were ≥100 mIU/mL. Our results showed that the rates of anti-VZV IgG seropositivity (χ2 = 328.957, P 3 m-1 y (P 1-3 m-

Auxin regulates cell division and elongation of the primordial cells through its concentration and then shaped the plant architecture. Cell division and elongation form the internode of soybean and result in different plant heights and lodging resistance. Yet the mechanisms behind are unclear in soybean. To elucidate the mechanism of the concentration difference of auxin related to stem development in soybean, samples of apical shoot, elongation zone, and mature zone from the developing stems of soybean seedlings, Charleston, were harvested and measured for auxin concentration distributions and metabolites to identify the common underlying mechanisms responsible for concentration difference of auxin. Distribution of indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), and methylindole-3-acetic acid (Me-IAA) were determined and auxin concentration distributions were found to have a complex regulation mechanism. The concentrations of IAA and Me-IAA in apical shoot were significantly different between elongation zone and mature zone resulting in an IAA gradient. Tryptophan dependent pathway from tryptamine directly to IAA or through indole-3-acetonitrile to IAA and from indole-3-propionic acid (IPA) to IAA were three primary IAA synthesis pathways. Moreover, some plant metabolites from flavonoid and phenylpropanoid synthesis pathways showed similar or reverse gradient and should involve in auxin homeostasis and concentration difference. All the data give the first insight in the concentration difference and homeostasis of auxin in soybean seedlings and facilitate a deeper understanding of the molecular mechanism of stem development and growth. The gathered information also helps to elucidate how plant height is formed in soybean and what strategy should be adopted to regulate the lodging resistance in soybean.

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 μg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 μg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.

Abstract Amorphous In–Ga–Zn-O (a-IGZO) thin-film transistor (TFT) memories are attracting many interests for future system-on-panel applications; however, they usually exhibit a poor erasing efficiency. In this article, we investigate voltage-polarity-dependent programming behaviors of an a-IGZO TFT memory with an atomic-layer-deposited ZnO charge trapping layer (CTL). The pristine devices demonstrate electrically programmable characteristics not only under positive gate biases but also under negative gate biases. In particular, the latter can generate a much higher programming efficiency than the former. Upon applying a gate bias pulse of +13 V/1 μs, the device shows a threshold voltage shift (ΔVth) of 2 V; and the ΔVth is as large as −6.5 V for a gate bias pulse of −13 V/1 μs. In the case of 12 V/1 ms programming (P) and −12 V/10 μs erasing (E), a memory window as large as 7.2 V can be achieved at 103 of P/E cycles. By comparing the ZnO CTLs annealed in O2 or N2 with the as-deposited one, it is concluded that the oxygen vacancy (VO)-related defects dominate the bipolar programming characteristics of the TFT memory devices. For programming at positive gate voltage, electrons are injected from the IGZO channel into the ZnO layer and preferentially trapped at deep levels of singly ionized oxygen vacancy (VO +) and doubly ionized oxygen vacancy (VO 2+). Regarding programming at negative gate voltage, electrons are de-trapped easily from neutral oxygen vacancies because of shallow donors and tunnel back to the channel. This thus leads to highly efficient erasing by the formation of additional ionized oxygen vacancies with positive charges.

Background: Previous studies have shown conflicting results about the benefits of pretreatment with intravenous thrombolysis before endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) with large vessel occlusions (LVOs). This study aimed to investigate the clinical efficacy and safety of EVT alone vs. bridging therapy (BT) in patients with AIS with LVOs.Methods: A systematic review with meta-analysis of all available studies comparing clinical outcomes between BT and EVT alone was conducted by searching the National Center for Biotechnology Information/National Library of Medicine PubMed and Web of Science databases for relevant literature from database inception to October 20, 2020.Results: A total of 93 studies enrolling 45,190 patients were included in the present analysis. In both unadjusted and adjusted analyses, BT was associated with a higher likelihood of 90-day good outcome (crude odds ratio [cOR] 1.361, 95% confidence interval [CI] 1.234–1.502 and adjusted OR [aOR] 1.369, 95% CI 1.217–1.540) and successful reperfusion (cOR 1.271, 95% CI 1.149–1.406 and aOR 1.267, 95% CI 1.095–1.465) and lower odds of 90-day mortality (cOR 0.619, 95% CI 0.560–0.684 and aOR 0.718, 95% CI 0.594–0.868) than EVT alone. The two groups did not differ in the occurrence of symptomatic intracranial hemorrhage (sICH) (cOR 1.062, 95% CI 0.915–1.232 and aOR 1.20, 95% CI 0.95–1.47), 24-h early recovery (cOR 1.306, 95% CI 0.906–1.881 and aOR 1.46, 95% CI 0.46–2.19), and number of thrombectomy device passes ≤ 2 (aOR 1.466, 95% CI 0.983–2.185) after sensitivity analyses and adjustment for publication bias.Conclusions: BT provides more benefits than EVT alone in terms of clinical functional outcomes without compromising safety in AIS patients with LVOs.

Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic responses to JAK inhibitors have been studied in clinical trials. Here, we report a novel STRBP-JAK2 fusion gene in a 21-year-old woman with Ph-like ALL. Although a normal karyotype was observed, a hitherto unreported JAK2 rearrangement was detected cytogenetically. STRBP-JAK2 fusion was identified by RNA sequencing and validated by Sanger sequencing. The Ph-like ALL proved refractory to traditional induction chemotherapy combined with ruxolitinib. The patient consented to infusion of autologous chimeric antigen receptor (CAR) T cells against both CD19 and CD22, which induced morphologic remission. Haplo-identical stem cell transplantation was then performed; however, she suffered relapse at just one month after transplantation. The patient subsequently received donor lymphocyte infusion after which she achieved and maintained a minimal residual disease negative remission. However, she succumbed to grade IV graft-versus-host disease 7 months post-transplant. In conclusion, this report describes a novel STRBP-JAK2 gene fusion in a Ph-like ALL patient with a very aggressive disease course, which proved resistant to chemotherapy combined with ruxolitinib but sensitive to immunotherapy. Our study suggests that CAR T-cell therapy may be a viable option for this type of leukemia.

AIM: To analyze the application value of optical coherence tomography(OCT)combined with isolated-check visual evoked potential(Ic-VEP)in the diagnosis and treatment of primary open angle glaucoma(POAG). METHODS: Prospective cohort study. Totally 32 eyes of 32 suspected glaucoma cases, 30 eyes of 30 early POAG cases, 25 eyes of 25 moderate and late POAG cases were selected from the patients treated in our hospital from October 2014 to May 2018 were enrolled, and 30 eyes of 30 normal subjects were selected as control group. All subjects received OCT, Ic-VEP, visual field test, measurement results were analyzed.RESULTS: The sensitivity and specificity of Ic-VEP in diagnose of early POAG was 83% and 93% respectively. The difference between the early POAG group and the suspected glaucoma group was no statistically significant in the signal-to-noise ratio of 8% SNR(P>0.05), but were statistically significant in other groups(PPP>0.05). The retinal nerve fiber layer(RNFL)thickness parameters in four groups became thinner with the aggravation of the disease, and the differences between the four groups were statistically significant(PP=0.08), the differences between the other groups were statistically significant(PCONCLUSION: OCT and Ic-VEP have high diagnostic ability for the early changes of POAG and can evaluate the degree of optic nerve injury, which can be combined used for early diagnosis and efficacy evaluation of POAG.

Using a new kind of alkenyl silicon phthalocyanine, styrene (St) and methacrylic acid as monomers and potassium persulfate as an initiator, carboxylated silicon phthalocyanine photosensitive microspheres were synthesized by in-situ emulsion copolymerization. The structure and morphology of the microspheres were characterized by Fourier transform infrared spectroscopy (FT-IR)and scanning electron microscopy. Fluorescence spectrometer was used to characterize the optical property of the microspheres. The experimental results show that silicon phthalocyanine molecules with flexible unsaturated side chains have good compatibility with styrene. With the presence of carboxyl groups, the as-prepared photosensitive microspheres show high monodispersity and stability. On the basis of this, 9,10-diphenylanthracene (DPA) as singlet oxygen indicator was used to evaluate the photosensitivity of the microspheres. In addition, we report a novel phenomenon that the microspheres can be controllable etched by light irradiation with the presence of DPA in a specific solvent.

Plant stress-associated proteins (SAPs) contain A20/AN1 zinc finger domains and are involved in plant response to abiotic stresses. In this study, we aimed to explore the biological function of tea plant CsSAPs. A total of 14 CsSAP genes were identified in the tea plant genome using a reference genome database (Camellia sinensis var. sinensis). The CsSAPs were divided into the following two groups: Group I, containing one AN1 domain and/or one A20 domain; and Group II, containing two AN1 domains and/or two C2H2 domains. The sequence alignments and conserved domains analysis indicated that the CsSAPs were highly structurally conserved in terms of amino acid sequence and protein structure. The CsSAPs showed different transcript levels in spatio-temporal expression and in response to cold and drought stress in tea plants. Furthermore, the expression of CsSAP12 was considerably upregulated under drought stress. The overexpression of CsSAP12 in transgenic tomatoes showed increased tolerance to drought stress compared with the wild type. Altogether, the results showed that CsSAP12 might be involved in drought stress. Thus, CsSAP12 might be a target gene in genetic engineering to improve drought tolerance in tea plants.

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) is a rare but heterogeneous subtype of MDS/MPN, with no specific genetic alterations and standard treatments. ASXL1, SRSF2, TET2, JAK2 and NRAS are commonly mutated in MDS/MPN-U. Double gene mutations could be detected in MDS/MPN-U, however, co-mutations of 3 and more genes in this disease entity are very rare. Here, we present a case of MDS/MPN-U with triple mutations involving JAK2, SF3B1, and TP53. After failure of traditional therapy including hydroxyurea and interferon-α, the patient received ruxolitinib monotherapy and achieved hematological response quickly. Though mutations in TP53 implied a poor prognosis in myeloid malignancies, this patient has maintained no AML transformation for 26 months since diagnosis. Further research on complex mutations in the pathogenesis and prognosis of MDS/MPN-U is warranted.

Introduction: Published data regarding the association between solute carrier family 30, member 8 (SLC30A8) rs13266634 polymorphism and type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) risks in Chinese population are in-consistent. The purpose of this meta-analysis was to evaluate the association between SLC30A8 rs13266634 and T2DM/IGR in a Chinese population.Material and Methods: Three English (PubMed, Embase, and Web of Science) and three Chinese databases (Wanfang, CNKI, and CBMD database) were used for searching articles from January 2005 to January 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated with the random-effect model. Trial sequential analysis was also utilized.Results: Twenty-eight case-control studies with 25,912 cases and 26,975 controls were included for SLC30A8 and T2DM. Pooled risk allele C frequency for rs13266634 was 60.6% (95%CI: 59.2–62.0%) in the T2DM group and 54.8% (95%CI: 53.2–56.4%) in the control group which had estimated OR of 1.23 (95%CI: 1.17–1.28). Individuals who carried major homozygous CC and heterozygous CT genotype were at 1.51 and 1.23 times higher risk of T2DM, respectively, than those carrying minor homozygous TT. The most appropriate genetic analysis model was the co-dominant model based on comparison of OR1, OR2 and OR3. Five articles that involved 4,627 cases and 6,166 controls were included for SLC30A8 and IGR. However, no association was found between SLC30A8 rs13266634 and IGR (C vs. T, OR = 1.13, 95%CI: 0.98–1.30, p = 0.082). TSA revealed that the pooled sample sizes of T2DM exceeded the estimated required information size but not the IGR.Conclusion: The present meta-analysis demonstrated that SLC30A8 rs13266634 was a potential risk factor for T2DM, and more studies should be performed to confirm the association between rs13266634 polymorphism and IGR.

The poly(ethyleneimine)-functionalized silica has been developed successfully as an effective adsorbent for the adsorption removal of Cu(II) ions from electroplating wastewater. The influences of pH, contact time and initial concentration of Cu(II) ions on the adsorption capacity and the effect of adsorbent dosage on the removal efficiency of Cu(II) ions from electroplating wastewater were investigated. The adsorption behaviors and mechanisms of Cu(II) ions onto poly(ethyleneimine)-functionalized silica were also studied in details. The uptake of Cu(II) ions on poly(ethyleneimine)-functionalized silica was constant in the range of pH 4-8. The poly(ethyleneimine)-functionalized silica offered a fast rate for the adsorption of Cu(II) ions and reached an equilibrium state within 30 min. The results of static batch experiment indicated that the maximum static adsorption capacity of Cu(II) ions on PEI-functionalized silica was 31.8 mg/g. The adsorption process was found to follow a pseudo-second-order rate mechanism. Langmuir adsorption isotherms fitted well in the experimental data. The optimum dosage of poly(ethyleneimine)-functionalized silica for the removal Cu(II) ions from electroplating wastewater was 10 g/L. The removal efficiency of Cu(II) ions from electroplating wastewater was 92.6%.Some scale-up experiments were also investigated to offer the reference for water treatment. The results showed that poly(ethyleneimine)-functionalized silica could be employed as an effective adsorbent for the removal of Cu(II) ions from electroplating wastewater.

Melatonin can increase plant resistance to stress, and exogenous melatonin has been reported to promote stress resistance in plants. In this study, a melatonin biosynthesis-related SlCOMT1 gene was cloned from tomato (Solanum lycopersicum Mill. cv. Ailsa Craig), which is highly expressed in fruits compared with other organs. The protein was found to locate in the cytoplasm. Melatonin content in SlCOMT1 overexpression transgenic tomato plants was significantly higher than that in wild-type plants. Under 800 mM NaCl stress, the transcript level of SlCOMT1 in tomato leaf was positively related to the melatonin contents. Furthermore, compared with that in wild-type plants, levels of superoxide and hydrogen peroxide were lower while the content of proline was higher in SlCOMT1 transgenic tomatoes. Therefore, SlCOMT1 was closely associated with melatonin biosynthesis confers the significant salt tolerance, providing a clue to cope with the growing global problem of salination in agricultural production.

One emerging principle is that neuromodulators, such as neuropeptides, regulate multiple behaviors, particularly motivated behaviors, e.g., feeding and locomotion. However, how neuromodulators act on multiple neural networks to exert their actions remains poorly understood. These actions depend on the chemical form of the peptide, e.g., an alternation of L- to D-form of an amino acid can endow the peptide with bioactivity, as is the case for the Aplysia peptide GdFFD (where dF indicates D-phenylalanine). GdFFD has been shown to act as an extrinsic neuromodulator in the feeding network, while the all L-amino acid form, GFFD, was not bioactive. Given that both GdFFD/GFFD are also present in pedal neurons that mediate locomotion, we sought to determine whether they impact locomotion. We first examined effects of both peptides on isolated ganglia, and monitored fictive programs using the parapedal commissural nerve (PPCN). Indeed, GdFFD was bioactive and GFFD was not. GdFFD increased the frequency with which neural activity was observed in the PPCN. In part, there was an increase in bursting spiking activity that resembled fictive locomotion. Additionally, there was significant activity between bursts. To determine how the peptide-induced activity in the isolated CNS is translated into behavior, we recorded animal movements, and developed a computer program to automatically track the animal and calculate the path of movement and velocity of locomotion. We found that GdFFD significantly reduced locomotion and induced a foot curl. These data suggest that the increase in PPCN activity observed in the isolated CNS during GdFFD application corresponds to a reduction, rather than an increase, in locomotion. In contrast, GFFD had no effect. Thus, our study suggests that GdFFD may act as an intrinsic neuromodulator in the Aplysia locomotor network. More generally, our study indicates that physiological and behavioral analyses should be combined to evaluate peptide actions.

Background. Pigment epithelium-derived factor (PEDF) is demonstrated to be elevated in diabetes patients. However, no reports have emerged in pregnant women with gestational diabetes mellitus (GDM). This study was undertaken to investigate serum PEDF levels in GDM women and to evaluate PEDF as a biomarker to predict diabetes postpartum. Methods. Serum PEDF concentration and clinical characteristics were detected in the pregnant women with GDM (n = 120) and without GDM (control group, n = 120). Results. PEDF levels were elevated in subjects with GDM versus controls. Univariate correlations showed that serum PEDF levels were positively correlated with fasting glucose and fasting insulin levels, respectively, and negatively correlated with adiponectin. Receiver operating characteristic (ROC) analysis demonstrated that the AUC of serum PEDF for diabetes mellitus in women postpartum was 0.893. Conclusion. Serum PEDF was elevated in pregnant women with GDM, which is probably an early detection marker for predicting development of GDM to diabetes mellitus.

Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood.

The miRNA processing genes play essential roles in the biosynthesis of mammalian miRNAs, and their genetic variants are involved in the development of various cancers. Our study aimed to determine the potential association between miRNA processing gene polymorphisms and cervical precancerous lesions. Five single nucleotide polymorphisms (SNPs), including Ran-GTP (RAN) rs14035, exportin-5 (XPO5) rs11077, DICER1 rs3742330, DICER1 rs13078, and TARBP2 rs784567, were genotyped in a case–control study to estimate risk factors of cervical precancerous lesions. The gene–environment interactions and haplotype association were estimated. We identified a 27% decreased risk of cervical precancerous lesions for individuals with minor G allele in DICER1 rs3742330 (odds ratio (OR) = 0.73, 95% confidence interval (95% CI) = 0.58–0.92, P = 0.009). The AG and AG/GG genotypes in DICER1 rs3742330 were also found to decrease the risk of cervical precancerous lesions (AG compared with AA: OR = 0.51, 95% CI = 0.35–0.73, P <0.001; AG/GG compared with AA: OR = 0.54, 95% CI = 0.39–0.77, P = 0.001). The GT haplotype in DICER1 had a risk effect on cervical precancerous lesions compared with the AT haplotype (OR = 1.36, 95% CI = 1.08–1.73, P = 0.010). A two-factor (DICER1 rs3742330 and human papillomavirus (HPV) infection) and two three-factor (model 1: rs3742330, passive smoking, and HPV infection; model 2: rs3742330, abortion history, and HPV infection) interaction models for cervical precancerous lesions were identified. In conclusion, the genetic variants in the miRNA processing genes and interactions with certain environmental factors might contribute to the risk of cervical precancerous lesions in southern Chinese women. [ABSTRACT FROM AUTHOR]