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Abstract The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m2/day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9–28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML.

Abstract This study proposes a smart grid model named “GridOptiPredict”, which aims to achieve efficient analysis and processing of power system data through deep fusion of deep learning and graph neural network, so as to improve the intelligent level and overall efficiency of power grid operation. The model integrates three core functions of load forecasting, power grid state sensing and resource optimization into one, forming a closely connected and complementary framework. Through carefully designed experimental scheme, the practical value and effectiveness of “Grid OptiPredict” model are fully verified from three aspects: accuracy of load forecasting, sensitivity of power grid state sensing and efficiency of resource allocation strategy. Experimental results show that the model has significant advantages in prediction accuracy, model stability and robustness, resource optimization, security, information security, social and economic benefits and user experience.

It is hard to accomplish fast semantic segmentation on large remote sensing images, since current neural networks with numerous parameters often rely on significant computational resources. Our team proposes an improved fast semantic segmentation model based on short-term dense-connection network (RepSTDC). We introduce a structure reparameterization and coordinate attention into STDC networks. By structure reparameterization, we transform the multi-branch structure into a comparable single-branch configuration during the inference process. By replacing the traditional channel attention with a coordinate attention mechanism, we enhance the attention mechanism with considering channel relationships and long-distance position information, and then it saves the memory usages. We conducted thorough experiments to assess the efficacy of network components of RepSTDC on the several benchmark datasets. Additionally, we compared our proposed approach with state-of-the-art methods. Our RepSTDC model can well balance the accuracy performances, computing speed, and memory usage in most cases. It achieves fast segmentation by significantly reducing parameters but without obviously compromising performances compared to other methods.

Abstract Background Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management. Methods This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children’s hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests. Results The study described 153 children aged 0–18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6–12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3–42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38–16 531.18), which was the heaviest among EBV-LPDs. Conclusions Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs.

Introduction:The diagnostic accuracy of traditional imaging examination in predicting ypT stage of rectal cancer after neoadjuvant therapy is significantly reduced, which would affect patients’ subsequent treatment choices. This study aimed to investigate the use of endorectal shear wave elastography (SWE) for diagnosing ypT0 stage of rectal cancer after neoadjuvant chemoradiotherapy (nCRT).Methods:Sixty patients with rectal cancer were prospectively recruited in this study. Data on endorectal ultrasound (ERUS) and SWE parameters were collected before nCRT and 6–8 weeks after nCRT. Postoperative pathological results were the gold standard for evaluating the diagnostic accuracy of SWE and ERUS in predicting the ypT0 stage of rectal cancer after nCRT. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of the SWE parameters that best corresponded to the ypT0 stage and analyze the sensitivity, specificity, and accuracy.Results:The diagnostic accuracies of using ERUS to predict the ypT and ypT0 stages of rectal cancer after nCRT were 58.1% (18/31) and 64.3% (9/14), respectively. The ROC curve was constructed with the lesion’s Emean, Emean corrected (EC), Emean difference (ED), Emean corrected differencede (ECD), Emean descendding rate (EDR) and Emean corrected descendding rate (ECDR) values after nCRT, the cut-off values of diagnosing the ypT0 stage were 64.40 kPa, 55.45 kPa, 72.55 kPa, 73.75 kPa, 50.15%, and 55.93%, respectively; the area under the curve (AUC) for diagnosing the ypT0 stage was 0.924, 0.933, 0.748, 0.729, 0.857 and 0.861, respectively. The EC value showed the best diagnostic performance.Conclusion:SWE could improve the accuracy of conventional ERUS in diagnosing the ypT0 stage of rectal cancer after nCRT. It is expected to become a new method to help predict pathological complete responses in clinical practice and provide new evidence for the watch-and-wait approach.

Background: This study aims to investigate the association between nine tag single nucleotide polymorphisms (SNPs) in the C3 gene locus and the risk of coronary artery disease (CAD) as well as lipid levels in the Chinese population, and to further explore the interactions between SNPs and environmental factors that may be associated with CAD risk. Methods: A case-control study was conducted to investigate the association between CAD and C3 gene polymorphisms in a hospital setting. The study consisted of 944 CAD patients with a mean age of 55.97 ± 10.182 years and 897 non-CAD controls with a mean age of 55.94 ± 9.162 years. There were 565 males and 288 females in the CAD group and 583 males and 314 females in the control group. TagSNPs in the C3 gene were identified by employing the improved multiplex ligation detection reaction (iMLDR) technique, and multifactor dimensionality reduction (MDR) analysis was utilized to investigate the C3 gene–environment and gene–gene interactions in relation to the risk of CAD. Results: Results of the polymorphism study indicated that the CC genotype of rs7257062 was more frequent in the CAD group compared to the control group (10.9% vs 7.7%), with a statistically significant difference (p = 0.009). Moreover, the TT and CC + CT genotype groups of rs7257062 in the CAD subgroup showed a significant difference in terms of serum triglyceride levels (2.326 ± 1.889 vs 2.059 ± 1.447, p = 0.019). Analysis of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) levels revealed no significant differences between the TT and CC + CT genotypes. Furthermore, no significant differences in serum lipid levels were observed between genotypes of the other SNPs. Multivariable logistic analysis, controlling for gender, age, body mass index (BMI), triglycerides (TG), TC, HDL-C, LDL-C, ApoA and ApoB, demonstrated that rs7257062 was still an independent risk factor of CAD (OR = 1.499, 95% CI: 1.036–2.168, p = 0.032). MDR analysis revealed that the rs7257062 interacted significantly with environmental factors such as smoking, diabetes, hypertension, BMI, and TG (p < 0.05). Conclusions: The rs7257062 variation of the C3 gene could be linked to both lipid balance and the risk of CAD. It is conceivable that the interplay between C3 polymorphisms and environmental elements could account for the etiology of CAD.

Canine distemper (CD), caused by canine distemper virus (CDV), is a highly contagious and lethal disease in domestic and wild carnivores. Although CDV live-attenuated vaccines have reduced the incidence of CD worldwide, low levels of protection are achieved in the presence of maternal antibodies in juvenile animals. Moreover, live-attenuated CDV vaccines may retain residual virulence in highly susceptible species and cause disease. Here, we generated several CDV DNA vaccine candidates based on the biscistronic vector (pIRES) co-expressing virus wild-type or codon-optimized hemagglutinin (H) and nucleocapsid (N) or ferret interferon (IFN)-γ, as a molecular adjuvant, respectively. Apparently, ferret (Mustela putorius furo)-specific codon optimization increased the expression of CDV H and N proteins. A ferret model of CDV was used to evaluate the protective immune response of the DNA vaccines. The results of the vaccinated ferrets showed that the DNA vaccine co-expressing the genes of codon-optimized H and ferret IFN-γ (poptiH-IRES-IFN) elicited the highest anti-CDV serum-neutralizing antibodies titer (1:14) and cytokine responses (upregulated TNF-α, IL-4, IL-2, and IFN-γ expression) after the third immunization. Following vaccination, the animals were challenged with a lethal CDV 5804Pe/H strain with a dose of 105.0 TCID50. Protective immune responses induced by the DNA vaccine alleviated clinical symptoms and pathological changes in CDV-infected ferrets. However, it cannot completely prevent virus replication and viremia in vivo as well as virus shedding due to the limited neutralizing antibody level, which eventually contributed to a survival rate of 75% (3/4) against CDV infection. Therefore, the improved strategies for the present DNA vaccines should be taken into consideration to develop more protective immunity, which includes increasing antigen expression or alternative delivery routes, such as gene gun injection.

BackgroundCongenital TORCH (Toxoplasma gondii (T. gondii), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV)) infections are associated with a variety of adverse prenatal and neonatal events, including miscarriage, malformations and developmental abnormalities, and they remain an issue that cannot be neglected in China. However, the current research focuses more on the general screening of TORCH in women of childbearing age, and the medical information of children hospitalized due to congenital and perinatal TORCH infections has not been described in detail. This study summarized and analyzed the epidemiological characteristics, clinical manifestations, length of stay (LOS), and the disease burden of hospitalized children diagnosed with congenital TORCH infections in 27 children's hospitals in China.MethodologyBased on the face sheet of discharge medical records (FSMRs) of hospitalized children in 27 tertiary children's hospitals collected in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE), we summarized and analyzed the epidemiological characteristics, clinical manifestations, LOS, the disease burden (in US dollars, USD) and potential risk factors for hospitalized children diagnosed with congenital toxoplasmosis, congenital rubella syndrome, congenital cytomegalovirus infection, and congenital HSV in 27 children's hospitals in China from 2015 to 2020.ResultsOne hundred seventy-three patients aged 0-ConclusionIn the present study, the hospitalization proportion due to congenital TORCH infection was extremely low (17.56 per 100,000 neonates), indicating that China's congenital TORCH infection prevention and control policies remain effective. The lowest proportion of patients was hospitalized with congenital toxoplasmosis, while the LOS was the longest. The economic burden of CRS was heavy, and infants are recommended be vaccinated against RV in a timely manner. Congenital CMV infections accounted for the largest proportion of patients, suggesting that the disease burden of congenital CMV infection cannot be ignored, and the prevention of congenital CMV infection during pregnancy is still an important issue that needs to pay attention. The expense of hospitalization for congenital HSV infection was relatively low, while the disease burden increases significantly when patients develop complications. These data illustrate the importance of improving screening for congenital TORCH infections in the early diagnosis and treatment of neonatal patients.

BackgroundViruses of the family Flaviviridae, including Japanese encephalitis virus (JEV), dengue virus (DENV), yellow fever virus (YFV) and hepatitis C virus (HCV), are widely distributed worldwide. JEV, DENV and YFV belong to the genus Flavivirus, whereas HCV belongs to the genus Hepacivirus. Children's symptoms are usually severe. As a result, rates of hospitalization due to infection with these viruses are high. The epidemiology and disease burden of hospitalized children have rarely been described in detail to date. The objective of this study was to report the general epidemiological characteristics, clinical phenotype, length of stay (LOS), burden of disease, and potential risk factors for hospitalized children infected with JEV, DENV, YFV, or HCV in Chinese pediatric hospitals.MethodologyA cross-sectional study of epidemiology and disease burden of children hospitalized for Flaviviridae virus infections between December 2015 and December 2020 in China was performed. Face sheets of discharge medical records (FSMRs) were collected from 27 tertiary children's hospitals in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE). Information on sociodemographic variables, clinical phenotype, and LOS as well as economic burden was included in FSMRs and compared using appropriate statistical tests.FindingsThe study described 490 children aged 0-15 years hospitalized for infections with Flaviviridae viruses. Japanese encephalitis (JE) cases are the highest, accounting for 92.65% of the total hospitalization cases caused by Flaviviridae virus infection. The incidence of JE peaked from July to October with a profile of a high proportion of severe cases (68.06%) and low mortality (0.44%). Rural children had a significantly higher incidence than urban children (91.63%). Most hospitalized dengue cases were reported in 2019 when dengue outbreaks occurred in many provinces of China, although only 14 dengue cases were collected during the study period. Yellow fever (YF) is still an imported disease in China. The hospitalizations for children with hepatitis C (HC) were not high, and mild chronic HC was the main clinical phenotype of patients. Among the four viral infections, JE had the highest disease burden (LOS and expenditure) for hospitalized children.ConclusionFirst, the present study reveals that JE remains the most serious disease due to Flaviviridae virus infection and threatens children's health in China. Many pediatric patients have severe illnesses, but their mortality rate is lower, suggesting that existing treatment is effective. Both JEV vaccination and infection control of rural children should represent a focus of study. Second, although the dual risks of indigenous epidemics and imports of DENV still exist, the prevalence of DENV in children is generally manageable. Third, YFV currently shows no evidence of an epidemic in China. Finally, the proportion of children with chronic hepatitis C (CHC) is relatively large among hospitalized children diagnosed with HCV. Thus, early and effective intervention should be offered to children infected with HCV to ease the burden of CHC on public health.

Objective. Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are mosquito-borne flaviviruses with sequence homology. ZIKV circulates in some regions where JEV also circulates, or where JE vaccination is used. Cross-immunity between flaviviruses exists, but the precise mechanisms remain unclear. We previously demonstrated that T cell immunity induced by the live-attenuated Japanese encephalitis (JE) SA14-14-2 vaccine conferred protective immunity against ZIKV infection in mice, which could even bypass antibody-dependent enhancement. However, the role of T cell immune, especially memory T cell subsets, in cross-reactive immune responses between JE vaccine and ZIKV in humans has not been reported. Methods. We examined central and effector memory CD4+ and CD8+ T cell (TCM and TEM) responses (including degranulation, cytokines, and chemokines) in the presence of JEV and ZIKV, respectively, by using qualified peripheral blood mononuclear cell samples from 18 children who had recently received a two-dose course of JE vaccine SA14-14-2 as well as seven children without JE vaccination. Results. Cross-reactive CD8+ TCM in response to ZIKV was characterized by secretion of IFN-γ, whereas CD8+ TEM did not show significant upregulation of functional factors. In the presence of ZIKV, IFN-γ and TNF-α expression was upregulated by CD4+ TEM, and the expression signature of CD4+ TCM is more cytotoxic potential. Conclusions. We profiled the cross-reactive memory T cell responses to ZIKV in JE vaccine recipients. These data will provide evidence for the mechanism of cross-reactive memory T cell immune responses between JEV and ZIKV and a more refined view of bivalent vaccine design strategy.

Building-integrated photovoltaic (BIPV) façades are a promising technique for improving building energy performance. This study develops energy simulation models of different photovoltaic-integrated shading devices (PVSDs) in single-story and multi-story office buildings. A cross-region study in China is carried out to explore the energy performance of PVSDs in five climate zones. The shading effect of the upper PVSDs is taken into account. The results show that (1) PVSDs can be applicable in hot and cold climates; shading effects lead to a notable difference in the optimal PVSDs style. The average comprehensive energy saving ratios of different PVSDs ranged from 16.12% (fixed PV louvres in the vertical plane) to 51.95% (lower single panel). The most rewarding PVSDs are for single-story buildings in Kunming and the least suitable are for multi-story buildings in Guangzhou. (2) In climate zones with little air-conditioning energy consumption, avoiding considerably increased lighting consumption by PVSDs is vital. (3) To reduce shading effects, solar panels with smaller widths or vertical placements can be adopted. In addition, the distance of the PV modules from the top edge of the windows is also critical. Building performance evaluation in the early design stage enables maximum benefits for the same input (total area of PV panels). The research methodology and data analysis presented can guide parameters design and the geographical applicability of PVSDs, providing a reference for optimal building energy performance.

Summary: Extending the structural hierarchy and complexity through small-molecular self-assembly is a powerful way to obtain large discrete, functional molecular architecture. A hydrogen-bonded supramolecular organic framework (HSOF) with nanometer-size pores is constructed in a solid state with simple guanosine-monomer self-assembly. To extend the hierarchy of the G-quartet self-assembly to a higher order than that of the traditional G-quadruplex, H-bond acceptors on the C-8 position of guanosine are introduced to establish inter-quadruplex linkage via H bonding to N(2)-HB from the neighboring G-quartet. After screening different C-8 substitution groups and various synthesis conditions, HSOF-G1a’ is obtained by solvent evaporation under diluted condition. Single-crystal X-ray structure reveals that cubic repeating units formed by G8 are the supermolecule secondary building block (SBU) with large pores (d = 34 Å). To our knowledge, this is the first G-quartet self-assembly with an organized structure beyond cylindrical G-quadruplexes.

Aspergillus flavus and Aflatoxins in grain crops give rise to a serious threat to food security and cause huge economic losses. In particular, aflatoxin B1 has been identified as a Class I carcinogen to humans by the International Agency for Research on Cancer (IARC). Compared with conventional methods, Surface-Enhanced Raman Scattering (SERS) has paved the way for the detection of Aspergillus flavus and Aflatoxins in grain crops as it is a rapid, nondestructive, and sensitive analytical method. In this work, the rapid detection of Aspergillus flavus and quantification of Aflatoxin B1 in grain crops were performed by using a portable Raman spectrometer combined with colloidal Au nanoparticles (AuNPs). With the increase of the concentration of Aspergillus flavus spore suspension in the range of 102–108 CFU/mL, the better the combination of Aspergillus flavus spores and AuNPs, the better the enhancement effect of AuNPs solution on the Aspergillus flavus. A series of different concentrations of aflatoxin B1 methanol solution combined with AuNPs were determined based on SERS and their spectra were similar to that of solid powder. Moreover, the characteristic peak increased gradually with the increase of concentration in the range of 0.0005–0.01 mg/L and the determination limit was 0.0005 mg/L, which was verified by HPLC in ppM concentration. This rapid detection method can greatly shorten the detection time from several hours or even tens of hours to a few minutes, which can help to take effective measures to avoid causing large economic losses.

The Signal lymphatic activation molecule (SLAM, also known as CD150) as the cellular receptor of canine distemper virus (CDV) plays an important role in the virus-host interaction. However, it is still unknown whether amino acid differences in the SLAM variable (V) region affect the formation of syncytia. Here, using raccoon dog SLAM (rSLAM) and mink SLAM (mSLAM), we performed SLAM-V homologous modeling, site-directed mutagenesis, and surface expression analysis, as well as a cell fusion assay, to study the interaction between SLAM and CDV. More specifically, our investigation focused on two amino acid residues (74 and 129) of SLAM, previously predicted to play a relevant role in receptor-ligand interaction. Our results indicated that only residues at position 60, 74, and 129 were different between rSLAM and mSLAM among the 29 amino acids that might interact with CDV H, and residues 74 and 129 were located in the interface region interacting with CDV H. The amino acid substitution at the positions of 74 have a significant effect on the expression of mSLAM. The SLAM-V74I mutation in mink significantly improved the cell fusion efficiency of CDV. In contrast, the SLAM-I74V mutation in the raccoon dog significantly decreased cell fusion efficiency. We conclude that residue 74 of SLAM plays an important role during the the formation of syncytia. Only when implementing CDV infection analysis, the rSLAM-Q129R can significantly decreased the mean number of syncytia, but the mSLAM-R129Q can't. Additionally, residue 60 show variability between rSLAM and mSLAM. We believe that our study makes a significant contribution to the literature because we provide molecular data, partially accounting for the differences in host membrane and virus interaction laying the foundation for further molecular work.

PDK1 (3-Phosphoinositide dependent protein kinase-1) is a member in the PI3K (phosphatidylinositol 3 kinase) pathway and is implicated in neurodevelopmental disease with microcephaly. Although the role of PDK1 in neurogenesis has been broadly studied, it remains unknown how PDK1 may regulate oligogenesis in the central nervous system (CNS). To address this question, we generated oligodendrocyte (OL) lineage cells specific PDK1 conditional knockout (cKO) mice. We find that PDK1 cKOs display abnormal white matter (WM), massive loss of mature OLs and severe defect in myelination in the CNS. In contrast, these mutants exhibit normal neuronal development and unchanged apoptosis in the CNS. We demonstrate that deletion of PDK1 severely impairs OL differentiation. We show that genetic or pharmacological inhibition of PDK1 causes deficit in the mammalian target of rapamycin (mTor) signaling and down-regulation of Sox10. Together, these results highlight a critical role of PDK1 in OL differentiation during postnatal CNS development.

Abstract The extensive environmental adaptability of the genus Paenibacillus is related to the enormous diversity of its gene repertoires. Paenibacillus sp. SSG-1 has previously been reported, and its agar-degradation trait has attracted our attention. Here, the genome sequence of Paenibacillus sp. SSG-1, together with 76 previously sequenced strains, was comparatively studied. The results show that the pan-genome of Paenibacillus is open and indicate that the current taxonomy of this genus is incorrect. The incessant flux of gene repertoires resulting from the processes of gain and loss largely contributed to the difference in genomic content and genome size in Paenibacillus. Furthermore, a large number of genes gained are associated with carbohydrate transport and metabolism. It indicates that the evolution of glycometabolism is a key factor for the environmental adaptability of Paenibacillus species. Interestingly, through horizontal gene transfer, Paenibacillus sp. SSG-1 acquired an approximately 150 kb DNA fragment and shows an agar-degrading characteristic distinct from most other non-marine bacteria. This region may be transported in bacteria as a complete unit responsible for agar degradation. Taken together, these results provide insights into the evolutionary pattern of Paenibacillus and have implications for studies on the taxonomy and functional genomics of this genus.

The hoverfly, Eupeodes corollae, is a worldwide natural enemy of aphids and a plant pollinator. To provide insights into the biology of this species, we examined its population genetic structure by obtaining 1.15-GB random genomic sequences using next-generation sequencing and developing genome-wide microsatellite markers. A total of 79,138 microsatellite loci were initially isolated from the genomic sequences; after strict selection and further testing of 40 primer pairs in eight individuals, 24 polymorphic microsatellites with high amplification rates were developed. These microsatellites were used to examine the population genetic structure of 96 individuals from four field populations collected across southern to northern China. The number of alleles per locus ranged from 5 to 13 with an average of 8.75; the observed and expected heterozygosity varied from 0.235 to 0.768 and from 0.333 to 0.785, respectively. Population genetic structure analysis showed weak genetic differentiation among the four geographical populations of E. corollae, suggesting a high rate of gene flow reflecting likely widespread migration of E. corollae in China.

Here we identified a functional MazEF-dr system in the exceptionally stress-resistant bacterium D. radiodurans. We showed that overexpression of the toxin MazF-dr inhibited the growth of Escherichia coli. The toxic effect of MazF-dr was due to its sequence-specific endoribonuclease activity on RNAs containing a consensus 5′ACA3′, and it could be neutralized by MazE-dr. The MazF-dr showed a special cleavage preference for the nucleotide present before the ACA sequence with the order by U>A>G>C. MazEF-dr mediated the death of D. radiodurans cells under sub-lethal dose of stresses. The characteristics of programmed cell death (PCD) including membrane blebbing, loss of membrane integrity and cytoplasm condensation occurred in a fraction of the wild-type population at sub-lethal concentration of the DNA damaging agent mitomycin C (MMC); however, a MazEF-dr mutation relieved the cell death, suggesting that MazEF-dr mediated cell death through its endoribonuclease activity in response to DNA damage stress. The MazEF-dr-mediated cell death of a fraction of the population might serve as a survival strategy for the remaining population of D. radiodurans under DNA damage stress.

Background To explore the symptom clusters of patients undergoing maintenance hemodialysis and construct a symptom network to identify the core symptoms and core symptom clusters, to provide reference for precise symptom management.Methods Conveniently selected 354 patients with maintenance hemodialysis were surveyed cross-sectionally using the general information questionnaire, the Dialysis Symptom Index and the Kidney Disease Questionnaire. Symptom clusters were extracted using exploratory factor analysis, and core symptom clusters were identified using hierarchical regression and network analysis.Results The most common and severe symptoms were fatigue, dry skin and itching, and the most distressing symptoms were fatigue, itching and trouble falling asleep. Within the symptom network, worry (rs = 1.0) had the highest strength, trouble staying asleep(rc = 0.01) had the highest closeness, and fatigue had the highest betweenness (rb = 30) and bridge strength (rbs = 0.53). A total of four symptom clusters were extracted, namely psychological symptom cluster, sleep disorder symptom cluster, uremia-related symptom cluster, and neurological symptom cluster. Hierarchical regression results showed that the psychological symptom cluster had the greatest impact on patients’ quality of life.Conclusions Fatigue was the most severe symptom and the bridge symptom, the uremia-related symptom cluster caused the greatest distress for patients, worry was the core symptom, and the psychological symptom cluster was identified as the core cluster. Clinical staff can provide effective symptom management and improve patient symptom burden by establishing intervention strategies centered on these results.

Rice empty glumes, also named sterile lemmas or rudimentary lemmas according to different interpretations, are distinct from lemmas in morphology and cellular pattern. Consistently, the molecular mechanism to control the development of lemmas is different from that of empty glumes. Rice LEAFY HULL STERILE1(OsLHS1) and DROOPING LEAF(DL) regulate the cellular pattern and the number of vascular bundles of lemmas respectively, while LONG STERILE LEMMA1 (G1)/ELONGATED EMPTY GLUME (ELE) and PANICLE PHYTOMER2 (PAP2)/OsMADS34 determine identities of empty glumes. Though some progress has been made, identities of empty glumes remain unclear, and genetic interactions between lemma genes and glume genes have been rarely elucidated. In this research, a new G1/ELE mutant g1-6 was identified and the phenotype was analyzed. Similar to previously reported mutant lines of G1/ELE, empty glumes of g1-6 plants transform into lemma-like organs. Furthermore, Phenotypes of single and double mutant plants suggest that, in addition to their previously described gene-specific functions, G1/ELE and OsLHS1 play redundant roles in controlling vascular bundle number, cell volume, and cell layer number of empty glumes and lemmas. Meanwhile, expression patterns of G1/ELE in osmads1-z flowers and OsLHS1 in g1-6 flowers indicate they do not regulate each other at the level of transcription. Finally, down-regulation of the empty glume gene OsMADS34/PAP2 and ectopic expression of the lemma gene DL, in the g1-6 plants provide further evidence that empty glumes are sterile lemmas. Generally, our findings provided valuable information for better understanding functions of G1 and OsLHS1 in flower development and identities of empty glumes.

The fat sand rats (Psammomys obesus) can easily induce obesity and acquire type 2 diabetes mellitus when they are fed with high-carbohydrate diets. P. obesus is often used as an animal model for studies on diabetes and obesity. We described 16,592 bp of P. obesus mtDNA that contains 13 protein-coding genes (PGCs), two rRNA genes (12S rRNA and 16S rRNA), 22 transfer RNA (tRNA) genes, and one control region (D-loop). The complete mitochondrial genome sequence provided here would be useful for further understanding the evolution of ratite and conservation genetics of P. obesus.

The Indian false vampire (Megaderma lyra), known as the greater false vampire bat, the Indian false vampire bat, and the greater false-vampire, is typical echolocation mammals. It has been listed in the IUCN Red List of threatened species and included in the Red Book of Endangered Animals in China. Herein, we described 17,055 bp of M. lyra mtDNA that includes 13 protein-coding genes (PGCs), two rRNA genes (12S rRNA and 16S rRNA), 22 transfer RNA (tRNA) genes, and one control region (D-loop). The complete mitochondrial genome sequence will provide new molecular biology information to further understand the genetic diversity of the M. lyra and to protect this population.

The cyclic AMP receptor protein family of transcription factors regulates various metabolic pathways in bacteria, and also play roles in response to environmental changes. Here, we identify four homologs of the CRP family in Deinococcus radiodurans, one of which tolerates extremely high levels of oxidative stress and DNA-damaging reagents. Transcriptional levels of CRP were increased under hydrogen peroxide (H2O2) treatment during the stationary growth phase, indicating that CRPs function in response to oxidative stress. By constructing all CRP single knockout mutants, we found that the dr0997 mutant showed the lowest tolerance toward H2O2, ultraviolet radiation, ionizing radiation, and mitomycin C, while the phenotypes of the dr2362, dr0834, and dr1646 mutants showed slight or no significant differences from those of the wild-type strain. Taking advantage of the conservation of the CRP-binding site in many bacteria, we found that transcription of 18 genes, including genes encoding chromosome-partitioning protein (dr0998), Lon proteases (dr0349 and dr1974), NADH-quinone oxidoreductase (dr1506), thiosulfate sulfurtransferase (dr2531), the DNA repair protein UvsE (dr1819), PprA (dra0346), and RecN (dr1447), are directly regulated by DR0997. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses showed that certain genes involved in anti-oxidative responses, DNA repair, and various cellular pathways are transcriptionally attenuated in the dr0997 mutant. Interestingly, DR0997 also regulate the transcriptional levels of all CRP genes in this bacterium. These data suggest that DR0997 contributes to the extreme stress resistance of D. radiodurans via its regulatory role in multiple cellular pathways, such as anti-oxidation and DNA repair pathways.

A series of N,N’-disubstituted-2-nitroethene-1,1-diamine and N,N’-disubstituted- N’’-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB) VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these compounds might be developed for treatment of opioid tolerance and dependence.

Background: This study aims to investigate the association between nine tag single nucleotide polymorphisms (SNPs) in the C3 gene locus and the risk of coronary artery disease (CAD) as well as lipid levels in the Chinese population, and to further explore the interactions between SNPs and environmental factors that may be associated with CAD risk. Methods: A case-control study was conducted to investigate the association between CAD and C3 gene polymorphisms in a hospital setting. The study consisted of 944 CAD patients with a mean age of 55.97 ± 10.182 years and 897 non-CAD controls with a mean age of 55.94 ± 9.162 years. There were 565 males and 288 females in the CAD group and 583 males and 314 females in the control group. TagSNPs in the C3 gene were identified by employing the improved multiplex ligation detection reaction (iMLDR) technique, and multifactor dimensionality reduction (MDR) analysis was utilized to investigate the C3 gene–environment and gene-gene interactions in relation to the risk of CAD. Results: Results of the polymorphism study indicated that the CC genotype of rs7257062 was more frequent in the CAD group compared to the control group (10.9% vs 7.7%), with a statistically significant difference (p = 0.009). Moreover, the TT and CC + CT genotype groups of rs7257062 in the CAD subgroup showed a significant difference in terms of serum triglyceride levels (2.326 ± 1.889 vs 2.059 ± 1.447, p = 0.019). Analysis of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) levels revealed no significant differences between the TT and CC + CT genotypes. Furthermore, no significant differences in serum lipid levels were observed between genotypes of the other SNPs. Multivariable logistic analysis, controlling for gender, age, body mass index (BMI), triglycerides (TG), TC, HDL-C, LDL-C, ApoA and ApoB, demonstrated that rs7257062 was still an independent risk factor of CAD (OR = 1.499, 95% CI: 1.036-2.168, p = 0.032). MDR analysis revealed that the rs7257062 interacted significantly with environmental factors such as smoking, diabetes, hypertension, BMI, and TG (p < 0.05). Conclusions: The rs7257062 variation of the C3 gene could be linked to both lipid balance and the risk of CAD. It is conceivable that the interplay between C3 polymorphisms and environmental elements could account for the etiology of CAD. [ABSTRACT FROM AUTHOR]