Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity.

Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.

Azacitidine combined with interferon-α for pre-emptive treatment of AML/MDS after allogeneic peripheral blood stem cell transplantation: A prospective phase II study.

This prospective clinical study aimed to evaluate the efficacy and safety of the pre-emptive treatment modality of azacitidine in combination with interferon-α (IFN-α) in AML/MDS patients post-transplantation. Forty-seven patients aged 17-62 were enrolled with 14 patients having completed the planned 12 cycles. Following initiation, 72.3% responded positively after the first cycle, peaking at 77.2% by the fifth cycle. Notably, 24 patients maintained sustained responses throughout a median follow-up of 1050 days (range, 866-1234). Overall survival, leukaemia-free survival and event-free survival probabilities at 3 years were 69.5%, 60.4% and 35.7% respectively. Cumulative incidences of relapse and non-relapse mortality were 36.5% and 4.3% respectively. Multivariate analysis identified that receiving pre-emptive treatment for fewer than six cycles and the absence of chronic graft-versus-host disease after intervention was significantly associated with poorer clinical outcomes. The combination of azacitidine with IFN-α was well-tolerated with no observed severe myelotoxicity, and the majority of adverse events were reversible and manageable. In conclusion, the use of azacitidine in conjunction with IFN-α as pre-emptive therapy is a safe and effective treatment to prevent disease progression in AML/MDS patients with MRD positivity post-allo-HSCT.

High-Performance Monolithic 3D Integrated Complementary Inverters Based on Monolayer n-MoS2 and p-WSe2.

Herein, the structure of integrated M3D inverters are successfully demonstrated where a chemical vapor deposition (CVD) synthesized monolayer WSe2 p-type nanosheet FET is vertically integrated on top of CVD synthesized monolayer MoS2 n-type film FET arrays (2.5 × 2.5 cm) by semiconductor industry techniques, such as transfer, e-beam evaporation (EBV), and plasma etching processes. A low temperature (below 250 °C) is employed to protect the WSe2 and MoS2 channel materials from thermal decomposition during the whole fabrication process. The MoS2 NMOS and WSe2 PMOS device fabricated show an on/off current ratio exceeding 106 and the integrated M3D inverters indicate an average voltage gain of ≈9 at VDD = 2 V. In addition, the integrated M3D inverter demonstrates an ultra-low power consumption of 0.112 nW at a VDD of 1 V. Statistical analysis of the fabricated inverters devices shows their high reliability, rendering them suitable for large-area applications. The successful demonstration of M3D inverters based on large-scale 2D monolayer TMDs indicate their high potential for advancing the application of 2D TMDs in future integrated circuits.

Low-dose anti-thymocyte globulin plus low-dose posttransplant cyclophosphamide-based regimen for prevention of graft-versus-host disease in haploidentical peripheral blood stem cell transplantation for pediatric patients with hematologic malignancies.

The low-dose anti-thymocyte globulin (ATG) plus low-dose post transplantation cyclophosphamide (PTCy) -based (low-dose ATG/PTCy-based) regimen had a promising activity in preventing of graft-versus-host disease (GVHD) in adult patients. However, its efficacy in pediatric patients remain to be defined. Here, we presented the findings from 35 pediatric patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with the new regimen for GVHD prophylaxis. The cumulative incidences (CIs) of grades II-III and III-IV acute GVHD (aGVHD) were 34% (95% CI, 17-48%) and 11% (95% CI, 0-21%) within 180 days post-transplantation, respectively. The CIs of chronic GVHD (cGVHD) and moderate-to-severe cGVHD within 2 years were 26% (95% CI, 7-41%) and 12% (95% CI, 0-25%), respectively. The 2-year probabilities of overall survival, relapse-free survival, and graft-versus-host disease and relapse-free survival were 89% (95% CI, 78-100%), 82% (95% CI, 68-98%) and 59% (95% CI, 43-80%), respectively. The CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation by day 180 were 37% (95% CI, 19-51%) and 20% (95% CI, 6-32%) respectively. These results strongly advocate for the efficacy of the low-dose ATG/PTCy-based regimen as a robust strategy for GVHD prevention in haplo-PBSCT for pediatric patients.

Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies.

PURPOSE: Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. METHODS: Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. RESULTS: Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. CONCLUSION: This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.

Immune reconstitution and survival of patients after allogeneic hematopoietic stem cell transplantation from older donors.

BACKGROUND: The impact of donor age on the immune reconstitution of patients with hematological malignancies who underwent hematopoietic cell transplantation (HCT) is unclear. METHOD: We retrospectively compared the outcomes of 381 patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from 308 donors under 50 years of age and 73 donors over 50 years of age. IVIG was regularly supplemented for patients in the first 3 months post-HCT. RESULTS: The counts of CD8+CD45RA+ naïve T cells were significantly lower in patients of the older donor group than in the younger donor group in the first year after PBSCT (190.6 cells/µl vs. 239.6 cells/µl, p = .018). Patients in the older donor group had significantly fewer CD19+ B cells on day +270 (123.4 cells/µl vs. 183.5 cells/µl, p = .021) and day +365 (169 cells/µl vs. 271.1 cells/µl, p = .01) after PBSCT. Serum IgA (.76 g/L vs. .97 g/L, p < .001) and IgM levels (.75 g/L vs. 1.04 g/L, p < .001) were significantly lower in patients in the older donor group from day +60 to +365 after PBSCT. The EBV reactivation rate within the first 3 months after PBSCT was significantly higher in patients in the older donor group (48.6% vs. 38.3%, p = .034). However, the incidences of CMV reactivation, II-IV acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), 3-year relapse rate, 3-year transplant-related mortality (TRM) and 3-year overall survival (OS) were not significantly different between the two groups. CONCLUSION: In conclusion, donors ≥50 years old were associated with inferior immune reconstitution and higher EBV reactivation in patients after PBSCT, but no change in OS.

Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.

Purpose: Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship. Method: In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations. Result: Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: USH2A, CYP4V2, PRPF31, RHO, RP1, CNGA1, CNGB1, EYS, PRPF3, RP2, RPGR, and TOPORS. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). USH2A (4/20, 20%) and CYP4V2 (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in USH2A1, USH2A2, PRPF31, RP2, TOPORS, CNGB1, and RPGR. Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in CYP4V2. Conclusion: Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. USH2A and CYP4V2 were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.

Tunable dielectric metasurfaces by structuring the phase-change material.

Metasurfaces have made great progress in the last decade for generating miniature and integrated optical devices. The optical properties of metasurfaces can be tuned dynamically by integrating with phase-change materials. However, the efficiency of tunable metasurfaces remains a bit low, which is a disadvantage for the realistic applications of metasurfaces. Here, we demonstrate the tunable dielectric metasurfaces by structuring the phase-change material Ge2Sb2Te5. The unit cell of metasurface is composed of several Ge2Sb2Te5 nanopillars with different geometric parameters, and the incident light interacts with different nanopillars at diverse phases of Ge2Sb2Te5, leading to various functions. By elaborately arranging the Ge2Sb2Te5 nanopillars, various tunable optical devices have been realized, including tunable beam steering, reconfigurable metalens and switchable wave plate. The refractive direction, focal length and polarization state can be tuned through the phase transition of Ge2Sb2Te5. The phase-change metasurfaces based on Ge2Sb2Te5 nanostructures could be used in cameras, optical microscopy and adaptive optics.

Immune reconstitution and survival of patients with parvovirus B19 related pure red cell aplasia after haplo-PBSCT.

Parvovirus B19 (PvB19) infection and PvB19 related pure red cell aplasia (PRCA) in recipients with allogeneic hematopoietic stem cell transplantation have been reported sporadically. However, clinical studies with large sample sizes are lacking, especially in patients undergoing HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). In addition, clinical features, immune reconstitution, and outcomes of these patients are not clear. We conducted a retrospective analysis of 164 patients who received haplo-PBSCT with low-dose anti-thymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide (PTCy)-based regimen as graft-versus-host disease (GVHD) prophylaxis. We analyzed the incidence of PvB19 related PRCA and compared the clinical characteristics, immune reconstitution, incidence of GVHD, relapse rate, and survival between patients with and without PvB19 related PRCA. A total of 14 (8.5%) recipients developed PvB19 related PRCA after a median of 5.3 months after haplo-PBSCT. These patients with PvB19 related PRCA had slower immune reconstitution, but similar incidences of GVHD, relapse rate, and overall survival compared with recipients without PvB19 related PRCA. PvB19 related PRCA indicated relative delayed and poor immune reconstitution of the recipients early after haplo-PBSCT. PvB19 related PRCA had no effects on GVHD, relapse, and survival.

Highly luminescent pH-responsive carbon quantum dots for cell imaging.

Carbon quantum dots (CDs) have attracted tremendous interest owing to their idiosyncratic functions and wide-ranging applications. However, it remains a great challenge to empolder an integrated CDs combining high luminescence, biocompatibility and luminescence color tunability for bioimaging via simple approach. In this work, pH-responsive carbon quantum dots (Si-CDs) with high luminescence (quantum yield = 74.8%) were fabricated by one-step hydrothermal method using (3-mercaptopropyl) triethoxysilane (KH-580) as modifier for the first time. The optical properties of the as-prepared Si-CDs can be controlled from obvious green-blue-violet transformation by altering the pH. More importantly, the change is reversible and repeatable. In addition, the Si-CDs have good biocompatibility and chemically inertin vitrocell system simulation. Such non-toxic, environmental friendly, low-cost, inert CDs materials are promising candidates for biomedical and pH-sensitive sensors.

Effects of dietary triiodothyronine or dopamine on small intestinal oxygen consumption in chicks.

This study aimed to investigate the effects of triiodothyronine (T3)- or dopamine (Dp)-supplemented diets on oxygen consumption by Na+, K+-ATPase activity in broiler chicks. Five groups, each with twenty-four 6-day-old chicks, randomly received one of the five dietary treatments: (1) Basal diet (commercial broiler rations with 23.0% crude protein and 3,133 kcal metabolizable energy/kg) or CON, (2) basal diet plus 0.7 µmol Dp/kg diet or Dp0.7, (3) basal diet plus 2.4 µmol Dp/kg diet or Dp2.4, (4) basal diet plus 1.9 µmol T3/kg diet or T1.9, and (5) basal diet plus 3.8 µmol T3/kg diet or T3.8 from 6 to 14 days of age. There were four replicates per treatment and 120 birds in total. At 14 days of age, three chicks from each replicate of each treatment were pooled into a flock and fed commercial broiler diets until 7 weeks of age. Compared to CON group, birds fed with T3-supplemented diets had lower thyroid, abdominal fat pad, gizzard and pancreas weight, and heavier heart weight adjusted for fasted body weight. Chicks with T1.9 had lower ileal densities at 14 day old compared with those in Dp groups or CON. Chicks with T3.8 exhibited greater duodenal and jejunal O2 consumptions as well as ouabain-sensitive O2 consumptions of jejunum and small intestine (duodenum, jejunum, and ileum) by 46.5%, 58.3%, 40.6%, and 26.4% increases, than those in CON. Partial correlation analysis revealed that the weight and length of the small intestine were negatively correlated with body weight gain. Oxygen consumption in the various small intestinal segments was negatively correlated with their respective densities (mg/mm2). In conclusion, a greater oxygen requirement for maintaining ouabain-sensitive respiration (Na+-K+-ATPase) in the intestine limits energy availability to support gastrointestinal tract growth and, thereby, may result in lower body weight gain.

Landmark-Based Scale Estimation and Correction of Visual Inertial Odometry for VTOL UAVs in a GPS-Denied Environment.

With the rapid development of technology, unmanned aerial vehicles (UAVs) have become more popular and are applied in many areas. However, there are some environments where the Global Positioning System (GPS) is unavailable or has the problem of GPS signal outages, such as indoor and bridge inspections. Visual inertial odometry (VIO) is a popular research solution for non-GPS navigation. However, VIO has problems of scale errors and long-term drift. This study proposes a method to correct the position errors of VIO without the help of GPS information for vertical takeoff and landing (VTOL) UAVs. In the initial process, artificial landmarks are utilized to improve the positioning results of VIO by the known landmark information. The position of the UAV is estimated by VIO. Then, the accurate position is estimated by the extended Kalman filter (EKF) with the known landmark, which is used to obtain the scale correction using the least squares method. The Inertial Measurement Unit (IMU) data are used for integration in the time-update process. The EKF can be updated with two measurements. One is the visual odometry (VO) estimated directly by a landmark. The other is the VIO with scale correction. When the landmark is detected during takeoff phase, or the UAV is returning to the takeoff location during landing phase, the trajectory estimated by the landmark is used to update the scale correction. At the beginning of the experiments, preliminary verification was conducted on the ground. A self-developed UAV equipped with a visual-inertial sensor to collect data and a high-precision real time kinematic (RTK) to verify trajectory are applied to flight tests. The experimental results show that the method proposed in this research effectively solves the problems of scale and the long-term drift of VIO.

Desymmetric Cyanosilylation of Acyclic 1,3-Diketones.

Diastereo- and enantioselective construction of vicinal stereocenters from easily available starting materials is a challenging task. Here, we report that a bifunctional catalyst prepared from dibutylmagnesium and a pipecolinol-derived tetradentate ligand can enable an asymmetric cyanosilylation of 1,3-diketones to forge a pair of neighboring and acyclic tetrasubstituted carbons. The high stereoselectivity results from the rigid conformation of the diketone in the catalyst pocket, where the Lewis acidic magnesium center, together with the free hydroxyl group as a putative hydrogen bond donor, bind with both carbonyls. Consequently, stereochemically well-defined cyanohydrin silyl ethers with a diverse collection of substituents were prepared. Their rapid derivatization to molecules of higher complexity, such as heterocycles, triols, and fused rings, were also demonstrated.

Reflective temperature sensor based on a fiber Bragg grating combined with a fiber loop ringdown technique.

In this paper, a reflective fiber sensing system combined with a fiber loop ringdown technique for temperature detection is proposed. A fiber Bragg grating (FBG) with an initial center wavelength of 1543.33 nm was set as the sensor head. The experimental results showed that the average sensitivity of temperature was 1.003 µs/°C in the temperature range of 30-38°C, and the resolution was 0.007°C, which is 14 times better than the current FBG sensing demodulator. In addition, the system has the advantages of simple structure, low cost, and insensitivity to optical power fluctuation.

Choroidal vascular changes in retinitis pigmentosa patients detected by optical coherence tomography angiography.

BACKGROUND: To evaluate choroidal vascular changes, including choriocapillaris (CC) and middle/large choroidal vessels, in retinitis pigmentosa (RP) patients using wide-angle optical coherence tomography angiography (OCTA) and to determine whether changes in the choroidal vascularity have a relationship with visual function and retinal structural changes. METHODS: 34 patients with a confirmed diagnosis of RP and 48 controls were recruited. All patients underwent detailed ophthalmologic and imaging examinations, including two types of OCTA (Optovue, 3 × 3 mm, 6 × 6 mm; VG-200, 12 × 12 mm). CC defects were defined according to the choroidal vascular structure in five degrees. To evaluate middle and large choroidal vascular changes, the choroidal vascularity index (CVI), which was the luminance volume to the total choroidal volume, was used. RESULTS: Defects of choroidal vascularity of RP eyes were detected in comparison to control eyes. The defects were observed in the CC layer with a concentric or lobular pattern at different degrees. CVI, which was used to reflect middle/large choroidal vascularity, decreased in the perifoveal, pararetinal and periretinal regions in the RP eyes. CC defects degree were correlated with the BCVA (p = 0.001, r = - 0.556), the Humphrey indexes (mean deviation, MD, p < 0.001, r = - 0.673; PVF, p = 0.003, r = - 0.639; 10° mean sensitivity, 10° MS, p = 0.002, r = - 0.651) and microperimetry index (mean sensitivity, MS, p < 0.001, r = - 0.807). The preserved CC area (mean value: 28.65 ± 12.50 mm2) was negatively correlated with MS measured by microperimetry (p = 0.005, r = - 0.449). Ordinary regression analysis revealed that the CC defect degree was associated with the CVI of perifovea (p = 0.002, 95% CI: - 102.14 to - 24.01), the EZ length (p = 0.006, 95% CI: - 0.006 to - 0.001) and the VAD (vascular area density) of the DCP (deep capillary plexus) in the fovea (p = 0.022, 95% CI: 0.038-0.478). No correlations were detected between BCVA and CVI in any retinal regions. No correlations were found between the CVI and the VAD in any retinal regions. CONCLUSION: The choroidal vascularity was widely defected in RP. Choriocapillaris and middle/large choroidal vascularity defects were correlated with each other. Visual function and retinal structural changes were found to be associated with choriocapillaris defects but not with middle/large choroidal vascular defects.

Methylenetrahydrofolate Reductase Gene C677T Polymorphism and Diabetic Retinopathy: a Meta-Analysis.

Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) polymorphism and diabetic retinopathy (DR). Methods A total of 6971 subjects including 2707 DR patients and 4264 controls from 23 studies were enrolled in the study. A random-effects model was applied to estimate the overall effects and the stratified effects of the MTHFR C677T polymorphism on the risk of DR, and study quality was also assessed. Results Strong associations were observed between the MTHFR C677T polymorphism and DR. The carries of MTHFR C677T were more likely to be found in the DR group in relative to the healthy control group with odds ratio 1.68, 2.55, and 2.31 respectively in allele contrast model (T vs. C, 95%CI: 1.29-2.18, P<0.001, I 2=78.4%), homozygous model (TT vs. CC, 95%CI: 1.70-3.83, P=0.008, I 2=54.4%) and dominant model (TT+CT vs. CC, 95%CI: 1.62-3.29, P<0.001, I 2=74.7%). This association can also be found in contrast to the Ncd (non-complicated diabetic mellitus) group (allele contrast, OR=1.50, 95%CI: 1.07-2.11, P=0.032, I 2=62.1%; homozygous, OR=2.39, 95%CI: 1.06-5.38, P=0.017, I 2=66.7%; dominant, OR=1.59, 95%CI: 0.97-2.62, P=0.056, I 2=56.5%). For the heterozygous model (CT vs. CC), the association was significant in contrast to the healthy control group (OR=1.46, 95%CI: 1.64-3.69, P=0, I 2=77.3%), while in contrast to the Ncd control group the association was not statistically meaningful (OR=1.38, 95%CI: 0.87-2.18, P=0.131, I 2=43.7%). For the recessive model, 1.92-fold increased risk was found only in contrast to the Ncd control group (95%CI: 1.07-3.43, P=0.064, I 2=55.0%). There was no significant association found in the models in contrast to the DM control group. Conclusion In this meta-analysis, we found an association between the MTHFR C677T polymorphism and DR, especially in contrast to the Ncd control group. Further studies are required to establish more definite relationship.

Effect of line and floor type on growth performance and feather characterization during the growth period of White Roman geese.

OBJECTIVE: The purpose of this study was to investigate whether goose growth and feather characteristics are influenced by their line and feeding surroundings, inclusive of floor materials and types, since there are no reports regarding these factors. METHODS: The 240 White Roman geese which were hatched and sex identified came from 3 commercial goose farms. They were randomly distributed to 24 pens depending on a completely random design. The study continued for 13 weeks and included 3 lines of commercial geese and 2 floor types (cement strip floor [CSF] or cement floor [CF]). RESULTS: The day one gosling weight from A farm was lower than other two farms (96 g vs 107 and 115 g; p<0.001). Afterwards, the body weight, back length, keel length, chest girth and main wing feather length among 3 farms showed no significance difference prior to 12 weeks. The CF group showed heavier body weight, shorter back length, longer keel length, shorter chest girth and shorter main wing feather length than the CSF group prior to 12 weeks. The down weight in the CF was heavier than the CSF group (57.1 g vs 41.8 g; p<0.01) prior to 13 weeks. CONCLUSION: The body weight showed the positive relations for dry feather weight (r = 0.59), down weight (r = 0.69), percent of the down weight of live body weight prior to 13 weeks (r = 0.61).

[A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China].

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

Catalytic Chemosensing Assay for Selective Detection of Methyl Parathion Organophosphate Pesticide.

Herein, a catalytic chemosensing assay (CCA), based on a bimetallic complex, [RuII (bpy)2 (CN)2 ]2 (CuI I)2 (bpy=2,2'-bipyridine), is described. This complex integrates a task-specific catalyst (CuI -catalyst) and a signaling unit ([RuII (bpy)2 (CN)2 ]) to specifically hydrolyze methyl parathion, a highly toxic organophosphate (OP) pesticide. The bimetallic complex catalyzed the hydrolysis of the phosphate ester to generate o,o-dimethyl thiophosphate (DTP) anion and 4-nitrophenolate. Intrinsically, 4-nitrophenolate absorbed UV/Vis light at λmax =400 nm, creating the first level of the chemosensing signal. DTP interacted with the original complex to displace the chromophore, [RuII (bpy)2 (CN)2 ], which was monitored by spectrofluorometry; this was classified as the second level of chemosensing signal. By integrating both spectroscopic and spectrofluorometric signals with a simple AND logic gate, only methyl parathion was able to provide a positive response. Other aromatic and aliphatic OP pesticides (diazinon, fenthion, meviphos, terbufos, and phosalone) and 4-nitrophenyl acetate provided negative responses. Furthermore, owing to the metal-catalyzed hydrolysis of methyl parathion, the CCA system led to the detoxification of the pesticide. The CCA system also demonstrated its catalytic chemosensing properties in the detection of methyl parathion in real samples, including tap water, river water, and underground water.

Synthesis of novel 6,7-dimethoxy-4-anilinoquinolines as potent c-Met inhibitors.

HGF/c-Met signalling pathway plays an important role in the development of cancers. A series of 6,7-dimethoxy-4-anilinoquinolines possessing benzimidazole moiety were synthesised and identified as potent inhibitors of the tyrosine kinase c-Met. Their in vitro biological activities against three cancer cell lines (A549, MCF-7, and MKN-45) were also evaluated. Most of these compounds exhibited moderate to remarkable potency. Among them, compound 12n showed the most potent inhibitory activity against c-Met with IC50 value of 0.030 ± 0.008 µM and it also showed excellent anticancer activity against the tested cancer cell lines at low micromolar concentration. Molecular docking verified the results and revealed the possible binding mode of the most promising compound 12n into the ATP-binding site of c-Met kinase.