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Background The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown.Methods A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden’s index were employed to assess discrimination.Results Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden’s index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices.Conclusions Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland China. Additionally, we provide a comprehensive review of the existing literature concerning CAIS with MDRs resulting from androgen receptor (AR) gene mutations. This study broadens the clinical spectrum of CAIS and offer novel insights for further exploration into Müllerian duct regression. A 14-year-old patient, initially raised as female, presented to the clinic with complaints of “primary amenorrhea.” Physical examination revealed the following: armpit hair (Tanner stage 2), breast development (Tanner stage 4 with bilateral breast nodule diameter of 7 cm), sparse pubic hair (Tanner stage 3), clitoris measuring 0.8 cm × 0.4 cm, separate urethral and vaginal openings, and absence of palpable masses in the bilateral groin or labia majora. The external genital virilization score was 0 points. Serum follicle-stimulating hormone level was 13.43 IU/L, serum luteinizing hormone level was 31.24 IU/L, and serum testosterone level was 14.95 nmol/L. Pelvic magnetic resonance imaging (MRI) did not reveal a uterus or bilateral fallopian tubes, but nodules on both sides of the pelvic wall indicated cryptorchidism. The karyotype was 46,XY. Genetic testing identified a maternal-derived hemizygous variation c.2359C > T (p.Arg787*) in the AR gene. During abdominal exploration, dysplastic testicles and a dysplastic uterus were discovered. Histopathological analysis revealed the presence of fallopian tube-like structures adjacent to the testicles. The CAIS patient documented in this study exhibited concurrent MDRs, thus expanding the spectrum of clinical manifestations of AIS. A review of prior literature suggests that the incidence of CAIS combined with histologically MDRs is not uncommon. Consequently, the identification of MDRs in AIS cases may represent an integral aspect of clinical diagnosis for this condition.

The bromodomain and extra-terminal (BET) proteins act as “readers” for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes. BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2, and is involved in the regulation of cell cycle and apoptosis. Meanwhile, BET inhibitors (BETi) have regulatory effects on immune checkpoints, immune cells, and cytokine expression. The role of BET proteins and BETi in a variety of tumors has been studied. This paper reviews the recent research progress of BET and BETi in hematologic tumors (mainly leukemia, lymphoma and multiple myeloma) from cellular level studies, animal studies, clinical trials, drug combination, etc. BETi has a promising future in hematologic tumors, and future research directions may focus on the combination with other drugs to improve the efficacy.

The presence of thiocyanate (SCN−) in irrigation water has adverse effects on both plant growth and crop output. Hydrogen sulfide (H2S) is an important gaseous signaling molecule that can alleviate SCN− stress. Flavonoids are secondary compounds produced by plants and are ubiquitous in the plant kingdom. They play important roles in several physiological and biochemical processes. To investigate the effect of exogenous H2S on the growth of early rice plants under SCN− stress, we carried out a hydroponic experiment focusing on the interaction of exogenous H2S with flavonoids. In this study, a hydroponic experiment was performed to investigate the behavior of SCN− when subjected to varying effective doses (EC20: 24.0 mg/L; EC50: 96.0 mg/L; and EC75: 300.0 mg/L). The findings indicated that the relative growth rate (RGR) of the plants treated with H2S + SCN− was greater than that of the plants treated with SCN− alone. Higher amounts of flavonoids were detected in the shoots than in the roots, with more variability in the shoots. The early warning level results showed that most of the flavonoids were present at levels I and II, while quercetin was present at level IV. Genetic expression variation factor (GEVF) analyses revealed an increase in the quantity of “promoter genes” with increasing SCN− concentration in both rice tissues. Furthermore, administering external H2S while exposing rice tissues to SCN− resulted in a considerable decrease in the levels of reactive oxygen species. This study provides novel insights into the regulation of flavonoid levels in rice plants by exogenous H2S, facilitating enhanced resistance to SCN− stress and promoting sustainable agriculture.

AIM: To investigate the bacterial flora and antibiotic susceptibility testing of conjunctival sac in adolescents after wearing orthokeratology(OK)lens.METHODS:A total of 101 adolescents aged 8 to 14 who admitted to outpatient department of Xi'an No.1 Hospital from September 2021 to August 2022 were recruited in this cross-sectional observational study. There were 51 cases wearing OK Lens(wearing group)and 50 patients not wearing contact lens(non-lens group), the right eye of all patients was selected into the group. The culture of bacterial flora in conjunctival sac between the two groups were compared, the species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the antibiotic susceptibility testing was carried out for the positive strains cultured in the wearing group.RESULTS:The positive rate of conjunctival sac bacterial cultured in the wearing group and the non-lens group was 68.6%(35/51)and 60.0%(30/50), respectively(P>0.05). In both groups, the bacteria with the highest detection rate were staphylococcus epidermidis and staphylococcus aureus. The sensitivity rates of the strains detected in the wearing group to drugs are as follows: Levofloxacin(98%), Moxifloxacin(98%), Gatifloxacin(98%), Cefuroxime(98%), Cefathiamidine(98%), Rifampicin(98%), Chloramphenicol(96%), Cefoxitin(95%), Clindamycin(80%), Gentamicin(74%), Fusidic acid(72%), Tobramycin(64%), Compound sulfamethoxazole(26%), Mezlocillin(10%), Azithromycin(6%), of which the sensitivity rate of Gram-positive cocci was 100% sensitive to Vancomycin.CONCLUSION:Gram-positive cocci are the main bacteria isolated from conjunctival sac of adolescents after wearing OK Lens. Wearing OK Lens will not significantly increase the positive rate of conjunctival sac bacterial flora. Results of antibiotic susceptibility testing may provide guidance for empirical medication in patients wearing OK lens after eye infection.

AbstractBackground: The assessment of severity is crucial in the management of community-acquired pneumonia (CAP). It remains unknown whether updating cut-off values of severity scoring systems orchestrate improvement in predictive accuracy.Methods: 3,212 patients with CAP were recruited to two observational prospective cohort studies. Three bettered scoring systems were derived from the corresponding well-established and extensively used pneumonia-specific severity scoring systems, i.e. pneumonia severity index, minor criteria and CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure, and age ≥65 years) score, with the updating cut-off values for tachypnea and low blood pressure. Cronbach α was employed to determine construct validity. Discrimination was valued by calculating the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI).Results: Respiratory rate ≥22/min and systolic blood pressure ≤100 mm Hg were performed better than respiratory rate ≥30/min and hypotension for predicting mortality in the derivation cohort, respectively (AUROC, 0.823 vs 0.519, 0.688 vs 0.622; NRI, 0.61, 0.13). Bettered scoring systems orchestrated higher convergences, indicated by greater Cronbach α and more decrease in Cronbach α if the updating cut-off values were deleted. The six scoring systems agreed well with one another. Bettered- pneumonia severity index, minor criteria and CURB-65 score showed higher associations with severity and mortality rates and demonstrated greater predictive accuracies for mortality compared with the corresponding original systems (AUROC, 0.939 vs 0.883, 0.909 vs 0.871, 0.913 vs 0.859; NRI, 0.113, 0.076, 0.108; respectively). The validation cohort confirmed a similar pattern.Conclusions: Updating cut-off values of severity scoring systems for CAP orchestrate improvement in predictive accuracy, suggesting that it may facilitate the rationalization of clinical triage decision-making and further reduce mortality. The current studies provide the first known prospective evidence of potential benefit of the updating cut-off values of severity scoring systems for CAP in predictive accuracy.Key messagesUpdating cut-off values were performed better for predicting mortality.Bettered scoring systems orchestrated higher convergences.Bettered scoring systems demonstrated greater predictive accuracies for mortality.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves’ disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic  cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

AIM: To compare the changes of corneal refractive power before and after wearing defocus rigid gas permeable contact lens(RGPCL)in children with high myopia, and to analyze its influence on corneal refractive power and astigmatism after wearing glasses.METHODS: Self-controlled before-after study. A total of 30 cases(60 eyes)of children aged 8-12, with high myopia who were treated and fitted with defocus RGPCL in the Optometry Center of Xi'an First Hospital from June 2019 to June 2020 were collected. Using TMS-4N corneal topography instrument to measure the corneal tangential refractive power at baseline and wearing lens for 0.5 and 1a, and analyze the nasal side(N), temporal side(T), superior(S)and inferior(I)of the maximum corneal refractive power values at the 4 axial directions and the changes of the corneal refractive power at the center were collected at the same time at 1 mm intervals. The changes of corneal refractive power at each point before and after wearing glasses were analyzed. The axial length, diopter and corneal topography were required to be measured after 0.5 and 1a, and the changes in axial length, spherical equivalent, astigmatism and corneal refraction compared with baseline were analyzed.RESULTS: The maximum corneal refractive power of nasal(N), temporal(T), superior(S)and inferior(I)side was significantly increased at 0.5 and 1a when wearing defocus RGPCL compared with that before wearing glasses, which all showed positive relative refractive power compared with the corneal refractive power at center and was significantly different from the negative relative refractive power before wearing lenses. The relative peripheral refractive power of the cornea changed in the direction of positive refractive power when the lenses were worn for 0.5 and 1a. Except for the increase in the peripheral negative refractive power at the T1 point, the peripheral refractive power at all points in the other axes increased significantly. After wearing for 0.5a, the corneal steep K value became flat by 0.11±0.10D, the simK value decreased by 0.20±0.18D, the corneal steep K value became flat by 0.10±0.12D after 1a, the average K value became flat by 0.02±0.05D, and the simK value decreased by 0.16±0.13D. There was no significant difference in corneal level K from the baseline after wearing glasses for 0.5 and 1a.CONCLUSIONS: The maximum refractive power of the cornea in the state of wearing defocus RGPCL is positive relative refractive power compared with the vertex of cornea, and the relative peripheral negative refractive power of the cornea at each point on the 4 axes changes from negative value to positive value. Within 1a of wearing glasses, the axial length and spherical equivalent increased compared with the baseline, while the amount of astigmatism decreased, and the corneal refractive power showed a trend of steep K and flattening.

Abstract Background Pulsatilla decoction (Bai-Tou-Weng-Tang, BTWT) is a classic formula prescription of a traditional Chinese medicine that is used to treat ulcerative colitis (UC). However, its active components and underlying mechanism of action remain unclear. In the present study, we aimed to identify potential immunomodulators from BTWT that act at therapeutic targets for UC. Methods The protective effects of BTWT granules were examined in mice with colitis induced by dextran sulfate sodium. The absorbed components of BTWT were identified using LC-MS, and selected protein targets of these components in UC were investigated using molecular docking. Results Oral administration of BTWT granules significantly alleviated disease severity and colon shortening, and inhibited the inflammatory response in mice with chronic colitis. In these mice, 11 compounds from the BTWT granules were detected in the serum and/or colon. The molecular docking study demonstrated that compounds from Radix pulsatillae, such as anemoside A3, interacted with STAT3 and S1PR1; compounds from Rhizoma coptidis and/or Cortex phellodendri, such as palmatine, interacted with JAK3, PD-1, and PD-L1; and components of Cortex fraxini such as aesculin interacted with S1PR1, JAK3, STAT3 and PD-L1. Further in-vitro experiments showing that the compounds inhibited TNF-α and IL-6 production and STAT3 activation in RAW 264.7 cells suggested that these compounds have immunomodulatory activities. Conclusion We revealed for the first time that 11 absorbed ingredients from BTWT were immunomodulators against therapeutic targets for UC. These findings suggest that the identified compounds are the active components of BTWT, and the identified protein targets underlie the mechanism of action of BTWT against UC.

Abstract Background: Sitosterolemia (STSL) is an extremely rare genetic disease. Xanthomas as the first symptom are frequently misinterpreted as familial hypercholesterolemia (FH) in children. Inappropriate treatment may deteriorate the condition of STSL. Objectives: To present the clinical and laboratory characteristics of xanthomatous children diagnosed with sitosterolemia in comparison with childhood FH with xanthomas. Methods: We summarized and compared the clinical characteristics of STSL and FH patients with xanthomas as the first manifestations and investigated the different indicators between the STSL and FH groups, as well as their diagnostic values for STSL. Results: Two tertiary pediatric endocrinology departments contributed ten STSL cases. Five of the STSL patients (50%) experienced mild anemia, whereas two (20%) had vascular complications. The xanthomas of the STSL group displayed morphologies comparable to those of the FH group. There were ten cases of homozygous FH (HoFH) with xanthomas as the predominant symptom of the control group who had no anemia. The serum cholesterol (Chol) levels of the STSL and FH groups were 12.57 (9.55 ~ 14.62) mmol/L and 17.45 (16.04 ~ 21.47) mmol/L, respectively (p value 0.002). The serum low-density lipoprotein cholesterol (LDL-c) levels of the STSL and FH groups were 9.26 ± 2.71 mmol/L and 14.58 ± 4.08 mmol/L, respectively (p value 0.003). Meanwhile, the mean platelet volume (MPV) levels of the STSL and FH groups were 11.00 (9.79 ~ 12.53) fl. and 8.95 (8.88 ~ 12.28) fl., respectively (p value 0.009). The anemia proportions of the STSL and FH groups were 50% and 0%, respectively (p value 0.033). The AUC values of Chol, LDL-c, MPV, hemoglobin (Hb) for the diagnosis of STSL were 0.910, 0.886, 0.869, 0.879, respectively. Chol ≤ 15.41 mmol/L, LDL-c ≤ 13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L were the best thresholds for diagnosing STSL with childhood xanthomas. Conclusion The xanthoma morphology of STSL patients resembles that of FH patients. Xanthomas as the initial symptom of a child with Chol ≤ 15.41 mmol/L, LDL-c≤13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L, he was most likely to have STSL.

Tong et al. describe a super pangenome assembled from long-read sequences of 545 wild and domesticated silkworms. Naturally selected (diapause, aposemantic coloration) or artificially selected (silk yield and fineness) sets of genes are delineated.

Gas emitted from landfills contains a large quantity of volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs), some of which are carcinogenic, teratogenic, and mutagenic, thereby posing a serious threat to the health of landfill workers and nearby residents. However, the global hazards of VOCs and SVOCs in landfill gas to human health remain unclear. To quantify the global risk distributions of these pollutants, we collected the composition and concentration data of VOCs and SVOCs from 72 landfills in 20 countries from the core database of Web of Science and assessed their human health risks as well as analyzed their influencing factors. Organic compounds in landfill gas were found to primarily result from the biodegradation of natural organic waste or the emissions and volatilization of chemical products, with the concentration range of 1 × 10-1–1 × 106 μg/m3. The respiratory system, in particular, lung was the major target organ of VOCs and SVOCs, with additional adverse health impacts ranging from headache and allergies to lung cancer. Aromatic and halogenated compounds were the primary sources of health risk, while ethyl acetate and acetone from the biodegradation of natural organic waste also exceeded the acceptable levels for human health. Overall, VOCs and SVOCs affected residents within 1,000 m of landfills. Air temperature, relative humidity, air pressure, wind direction, and wind speed were the major factors that influenced the health risks of VOCs and SVOCs. Currently, landfill risk assessments of VOCs and SVOCs are primarily based on respiratory inhalation, with health risks due to other exposure routes remaining poorly elucidated. In addition, potential health risks due to the transport and transformation of landfill gas emitted into the atmosphere should be further studied.

Brown adipose tissue (BAT) represents a valuable target for treating obesity in humans. BAT losses of thermogenic capacity and gains a “white adipose tissue-like (WAT-like)” phenotype (BAT whitening) under thermoneutral environments, which could lead to potential low therapy responsiveness in BAT-based obesity treatments. However, the epigenetic mechanisms of BAT whitening remain largely unknown. In this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). RNA-sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were performed to investigate transcriptome and chromatin accessibility of BATs at the four whitening stages, respectively. Our data showed that many genes and chromatin accessible regions (refer to as “peaks”) were identified as significantly changed during BAT whitening in rabbits. The BAT-selective genes downregulated while WAT-selective genes upregulated from D0 to Y2, and the de novo lipogenesis-related genes reached the highest expression levels at D85. Both the highly expressed genes and accessible regions in Y2 were significantly enriched in immune response-related signal pathways. Analysis of different relationships between peaks and their nearby genes found an increased proportion of the synchronous changes between chromatin accessibility and gene expression during BAT whitening. The synergistic changes between the chromatin accessibility of promoter and the gene expression were found in the key adipose genes. The upregulated genes which contained increased peaks were significantly enriched in the PI3K-Akt signaling pathway, steroid biosynthesis, TGF-beta signaling pathway, osteoclast differentiation, and dilated cardiomyopathy. Moreover, the footprinting analysis suggested that sequential regulation of potential transcription factors (TFs) mediated the loss of thermogenic phenotype and the gain of a WAT-like phenotype of BAT. In conclusion, our study provided the transcriptional and epigenetic frameworks for understanding BAT whitening in rabbits for the first time and might facilitate potential insights into BAT-based obesity treatments.

Acute liver injury (ALI) is a disease that seriously threatens human health and life, and a dysregulated inflammation response is one of the main mechanisms of ALI induced by various factors. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein with multiple biological functions. At present, studies on PEBP4 exist mainly in the field of tumors and rarely in inflammation. This study aimed to explore the potential roles and mechanisms of PEBP4 on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALI. PEBP4 was downregulated after treatment with LPS/D-GalN in wild-type mice. PEBP4 hepatocyte-conditional knockout (CKO) aggravated liver damage and repressed liver functions, including hepatocellular edema, red blood cell infiltration, and increased aspartate aminotransferase (AST)/alanine aminotrans-ferase (ALT) activities. The inflammatory response was promoted through increased neutrophil infiltration, myeloperoxidase (MPO) activities, and cytokine secretions (interleukin-1β, IL-1β; tumor necrosis factor alpha, TNF-α; and cyclooxygenase-2, COX-2) in PEBP4 CKO mice. PEBP4 CKO also induced an apoptotic effect, including increasing the degree of apoptotic hepatocytes, the expressions and activities of caspases, and pro-apoptotic factor Bax while decreasing anti-apoptotic factor Bcl-2. Furthermore, the data demonstrated the levels of Toll-like receptor 4 (TLR4), phosphorylation-inhibitor of nuclear factor kappaB Alpha (p-IκB-α), and nuclear factor kappaB (NF-κB) p65 were upregulated, while the expressions of cytoplasmic IκB-α and NF-κB p65 were downregulated after PEBP4 CKO. More importantly, both the NF-κB inhibitor (Ammonium pyrrolidinedithiocarbamate, PDTC) and a small-molecule inhibitor of TLR4 (TAK-242) could inhibit TLR4/NF-κB signaling activation and reverse the effects of PEBP4 CKO. In summary, the data suggested that hepatocyte-conditional knockout of PEBP4 aggravated LPS/D-GalN-induced ALI, and the effect is partly mediated by activation of the TLR4/NF-κB signaling pathway.

Abstract Background CCN1 plays a crucial role in the modulation of cardiovascular diseases. However, whether CCN1 genetic variants are involved in the susceptibility of ACS remains unknown. Hence, the present study investigates the association between CCN1 polymorphisms and ACS among Han and Uygur populations in Xinjiang, China. Results In this case-control study, 1234 Han (547 ACS patients and 687 controls) and 932 Uygur (471 ACS patients and 461 controls) were genotyped using SNPscanTM for three single-nucleotide polymorphisms (SNPs, rs6576776, rs954353, and rs3753794) of the human CCN1 gene. In the Uygur population, we found that the detected frequencies of the C allele (25.3% vs. 18.3%, P

Abstract Macrophage migration inhibitory factor (MIF) is an essential mediator of atherosclerotic plaque progression and instability leading to intracoronary thrombosis, therefore contributing to coronary artery disease (CAD). In this study, we investigated the relationship between MIF gene polymorphism and CAD in Chinese Han population. Three single nucleotide polymorphisms (SNP, rs755622, rs1007888 and rs2096525) of MIF gene were genotyped by TaqMan genotyping assay in 1120 control participants and 1176 CAD patients. Coronary angiography was performed in all CAD patients and Gensini score was used to assess the severity of coronary artery lesions. The plasma levels of MIF and other inflammatory mediators were measured by ELISA. The CAD patients had a higher frequency of CC genotype and C allele of rs755622 compared with that in control subjects (CC genotype: 6.5% vs. 3.9%, P = 0.008, C allele: 24.0% vs. 20.6%, P = 0.005). The rs755622 CC genotype was associated with an increased risk of CAD (OR: 1.804, 95%CI: 1.221–2.664, P = 0.003). CAD patients with a variation of rs755622 CC genotype had significantly higher Gensini score compared with patients with GG or CG genotype (all P

Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs–lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan–Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.

Abstract Background Anthocyanins, which have important biological functions and have a beneficial effect on human health, notably account for pigmentation in purple-fleshed sweet potato tuberous roots. Individual regulatory factors of anthocyanin biosynthesis have been identified; however, the regulatory network of anthocyanin biosynthesis in purple-fleshed sweet potato is unclear. Results We functionally determined that IbMYB340 cotransformed with IbbHLH2 in tobacco and strawberry receptacles induced anthocyanin accumulation, and the addition of IbNAC56a or IbNAC56b caused increased pigmentation. Furthermore, we confirmed the interaction of IbMYB340 with IbbHLH2 and IbNAC56a or IbNAC56b via yeast two-hybrid and firefly luciferase complementation assays; these proteins could form a MYB340-bHLH2-NAC56a or MYB340-bHLH2-NAC56b transcriptional complex to regulate anthocyanin biosynthesis by binding to the IbANS promoter rather than the IbUFGT promoter. Furthermore, it was found by a transient expression system in tobacco leaves that IbMYB44 could decrease anthocyanin accumulation. Moreover, the interaction of IbMYB44 with IbMYB340 and IbNAC56a or IbNAC56b was verified. This result suggested that IbMYB44 acts as a repressor of anthocyanin in sweet potato. Conclusions The repressor IbMYB44 affected anthocyanin biosynthesis by competitively inhibiting the IbMYB340-IbbHLH2-IbNAC56a or IbMYB340-IbbHLH2-IbNAC56b regulatory complex formation. Overall, the present study proposed a novel regulatory network whereby several vital TFs play key roles in regulating anthocyanin biosynthesis, and it provides strong insight into the potential mechanism underlying anthocyanin biosynthesis in sweet potato tuberous roots with purple color.

Abstract Background The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS items to develop a weighted ESS scoring system improve the accuracy of the AHI prediction? It is warranted to explore the intriguing hypotheses. Methods Seven hundred fifty-six adult patients with suspicion of obstructive sleep apnoea syndrome (OSAS) were prospectively recruited to a derivation cohort. This was tested against a prospective validation cohort of 810 adult patients with suspected OSAS. Each ESS item’s increased odds ratio for the corresponding AHI was calculated using univariate logistic regression. The receiver operating characteristic curves were created and the areas under the curves (AUCs) were calculated to illustrate and compare the accuracy of the indices. Results The higher the ESS item-score, the closer the relationship with the corresponding AHI. The odds ratios decreased as a result of the increased AHI. The ESS items were of unequal weight in predicting the corresponding AHI and a weighted ESS was developed. The coincidence rates with the corresponding AHI, body mass indices, and neck circumferences rose as the scores increased, whereas nocturnal nadir oxygen saturations decreased, and the weighted ESS was more strongly associated with these indices, compared with the ESS. The capability in predicting the patients without OSAS or with severe OSAS was strong, especially the latter, and the weighted ESS orchestrated manifest improvement in screening the patients with simple snoring. The patterns of sensitivities, specificities, and Youden’s indices of the four ranks of weighted ESS for predicting the corresponding AHI were better than those of the ESS, and the AUCs of weighted ESS were greater than the corresponding areas of ESS in the two cohorts. Conclusions The weighted ESS orchestrated significant improvement in predicting the AHI, indicating that the capability in predicting the patients without OSAS or with severe OSAS was strong, which might have implications for clinical triage decisions to prioritize patients for polysomnography.

"AIM: To determine moxonidine in aqueous humor and iris-ciliary body by reversed-phase high performance liquid chromatography (RP-HPLC), and to evaluate the retinal neuroprotective effect after topical administration with moxonidine in a high intraocular pressure (IOP) model. METHODS: The eyes of albino rabbits were administered topically and ipsilaterally with 0.2% moxonidine. A RP-HPLC method was employed for the identification and quantification of moxonidine between 2 and 480min, which presented in the aqueous humor and iris-ciliary body. Flash electroretinography (F-ERG) amplitude and superoxide dismutase (SOD) level were measured between day 1 and day 15 after topical administration with moxonidine in a rabbit model of high IOP. Histological and ultrastructural observation underwent to analyze the changes of retinal morphology, the inner retinal layers (IRL) thickness, and retinal ganglion cell (RGC) counting. RESULTS: Moxonidine was detectable between 2 and 480min after administration, and the peak concentration developed both in the two tissues at 30min, 0.51 µg/mL in aqueous humor and 1.03 µg/g in iris-ciliary body. In comparison to control, F-ERG b-wave amplitude in moxonidine eyes were significantly differences between day 3 and day 15 (P

Objective: Mifepristone (RU486), one of the most common medications for artificial abortion, attenuates the immunoregulatory effects of progesterone. However, the specific immune regulatory mechanism of RU486 in abortion remains unknown. We intended to investigate the immunomodulatory effects of RU486 on abortion. Methods: Sixty female mice were divided into the control group (0 mg RU486) and RU486 group (2 mg/kg RU486). The uterus, peripheral blood, and spleen were obtained for isolation of specific cell types. The population and phenotype of immune cells in the decidua, peripheral blood, and spleen were analyzed using flow cytometry. Statistical differences between groups were determined using two-tailed t- test. For all statistical tests, P < 0.05 was considered statistically significant. Results: RU486 effectively induced abortion in pregnant mice, with a significantly higher number of decidual macrophages (dMφ) (control group = 25.55% ± 2.467%, RU486 group = 19.41% ± 1.423%; P < 0.05), especially the major histocompatibility complex IIhigh subset. No difference in Mφ number was observed in the spleen or peripheral blood. Moreover, the dMφ from mice with RU486-induced abortion displayed a remarkable activated phenotype, with increased expressions of inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin (IL)-12 but decreased expressions of arginase-1 and IL-10. We also found elevated levels of decidual CD4+ T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γ and a lower level of the anti-inflammatory cytokines, IL-4 and IL-10. Conclusions: We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφ activation and the adaptive response of CD4+ T-cells present in the decidua but not the periphery.

AIM: To evaluate the efficacy of phacoemulsification and intraocular lens implantation combined with goniosynechialysis in the treatment of chronic angle-closure glaucoma.METHODS: Thirty-three patients(35 eyes)with primary chronic angle-closure glaucoma and cataract were enrolled in the Department of Ophthalmology, Xi'an First Hospital from May 2018 to November 2018. The best corrected visual acuity, intraocular pressure, central anterior chamber depth, angle-opening distance at 500μm from the scleral spur, trabecular iris angle, angle closure or adhesion were compared between preoperative and postoperative 6mo.RESULTS: The best corrected visual acuity of 34 eyes(97%)was improved after operation. 27 eyes(77%)did not need any intraocular pressure lowering drugs after operation, and the intraocular pressure was kept below 21mmHg. The average value of anterior chamber depth, angle-opening distance at 500μm from the scleral spur and trabecular iris angle(2.04±0.31mm, 0.132±0.033μm, 15.44°±3.10°)before operation were significantly lower than the postoperative mean values(3.26±0.29mm, 0.407±0.038μm, 34.26°±3.60°). The range of angle closure or adhesion decreased after operation, and the difference was statistically significant. CONCLUSION: Phacoemulsification with intraocular lens implantation and goniosynechialysis is an effective way to treat primary chronic angle-closure glaucoma.

Sweet potato decays easily due to its high respiration rate and reactive oxygen species (ROS) accumulation during postharvest storage. In this study, we explored the relationship between antioxidant capacity in leaves and storage properties in different sweet potato cultivars, the tuberous roots of 10 sweet potato cultivars were used as the experimental materials to analyze the storage property during storage at 11–15°C. According to the decay percentage after 290 days of storage, Xu 32 was defined as a storage-tolerant cultivar (rot percentage less than 25%); Xu 55-2, Z 15-1, Shangshu 19, Yushu, and Zhezi 3 as above-moderate storage-tolerant cultivars (rot percentage ranging from 25 to 50%); Sushu 16, Yanshu 5, and Hanzi as medium-storable cultivars (rot percentage 50–75%); and Yan 25 as a storage-sensitive cultivar (rot percentage greater than 75%). Meanwhile, analysis of the α-amylase activity in root tubers of the 10 sweet potato cultivars during storage indicated that α-amylase activity was lowest in the storage-tolerant cultivar Xu 32 and highest in the storage-sensitive cultivar Yan 25. Evaluation of antioxidant enzyme activities and ROS content in the leaves of these 10 cultivars demonstrated that cultivar Xu 32, which showed the best storage property, had higher antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD)] but lower lipoxygenase (LOX) activity, hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents, and superoxide anion radical (O2⋅–) production rates compared with those of the storage-sensitive cultivar Yan 25 and the medium-storability cultivars Hanzi, Yanshu 5, and Sushu 16. Additionally, principal component analysis (PCA) suggested that sweet potato cultivars with different storage properties were clustered separately. Correlation and heat map analysis further indicated that CAT, APX, POD, and SOD activities were negatively correlated with α-amylase activity, while LOX activity and MDA and H2O2 contents were negatively correlated with the storage property of sweet potato. Combined, our findings revealed that storage property is highly correlated with antioxidant capacity in sweet potato leaves and negatively correlated with α-amylase activity in tuberous roots, which provides a convenient means for the screening of storage-tolerant sweet potato cultivars.

Due to their strong bacterial binding and bacterial toxicity, cationic liposomes have been utilized as effective antibacterial materials in many studies. However, few researchers have systematically compared their antibacterial activity with their mammalian cell cytotoxicity or have deeply explored their antibacterial and cytotoxicity mechanisms. Here, we prepared a series of cationic liposomes (termed CLs) using dimethyldioctadecylammonium chloride (DODAC) and lecithin at different molar ratios. CLs have the ability to effectively bind with Gram-positive and Gram-negative bacteria through electrostatic and hydrophobic interactions. Further, the CLs with high molar ratios of DODAC (30 and 40 mol%) can disrupt the bacterial wall/membrane, efficiently inducing the production of reactive oxygen species (ROS). More importantly, we carefully compared the antibacterial activity and the mammalian cell cytotoxicity of various CLs differing in DODAC contents and liposomal concentrations and revealed that, whether they are bacterial or mammalian cells, an increasing DODAC content in CLs can lead to an elevated cytotoxicity level. Further, there exists a critical DODAC contents (>20 mol%) in CLs to endow them with effective antibacterial ability. However, the variation in the DODAC content and liposomal concentration of CLs has different degrees of influence on the antibacterial activity or cytotoxicity. For example, CLs at high DODAC content (i.e., CL0.3 and CL0.4) could effectively kill both types of bacterial cells but only cause negligible toxicity to mammalian cells. We believe that a systematic comparison between the antibacterial activity and the cytotoxicity of CLs with different DODAC contents will provide an important reference for the potential clinical applications of cationic liposomes.

Rapid and accurate differentiation between live and dead cells is highly desirable for the evaluation of cell viability. Here, we report the application of the orange-emitting sulfur-doped organosilica nanodots (S-OSiNDs) for ultrafast (30 s), ultrasensitive (1 μg/mL), and universal staining of the dead bacterial, fungal, and mammalian cells but not the live ones, which satisfies the requirements of a fluorescent probe that can specifically stain the dead cells. We further verify that the fluorescence distribution range of S-OSiNDs (which are distributed in cytoplasm and nucleus) is much larger than that of the commercial dead/fixed cell/tissue staining dye RedDot2 (which is distributed in the nucleus) in terms of dead mammalian cell staining, indicating that S-OSiNDs possess a better staining effect of dead cells than RedDot2. Overall, S-OSiNDs can be used as a robust fluorescent probe for ultrafast and accurate discrimination between dead and live cells at a single cell level, which may find a variety of applications in the biomedical field.

Abstract Natural killer (NK) cells preferentially accumulate at maternal–foetal interface and are believed to play vital immune‐modulatory roles during early pregnancy and related immunological dysfunction may result in pregnant failure such as recurrent miscarriage (RM). However, the mechanisms underlying the establishment of maternal–foetal immunotolerance are complex but clarifying the roles of decidual NK (dNK) cells offers the potential to design immunotherapeutic strategies to assist RM patients. In this report, we analysed RNA sequencing on peripheral NK (pNK) and decidual NK cells during early pregnancy; we identified an immunomodulatory dNK subset CXCR4+CD56brightdNK and investigated its origin and phenotypic and functional characteristics. CXCR4+CD56brightdNK displayed a less activated and cytotoxic phenotype but an enhanced immunomodulatory potential relative to the CXCR4 negative subset. CXCR4+CD56brightdNK promote Th2 shift in an IL‐4‐dependent manner and can be recruited from peripheral blood and reprogramed by trophoblasts, as an active participant in the establishment of immune‐tolerance during early pregnancy. Diminished CXCR4+ dNK cells and their impaired ability to induce Th2 differentiation were found in RM patients and mouse models of spontaneous abortion. Moreover, adoptive transfer of CXCR4+ dNK cells to NK‐deficient (Nfil3–/–) mice showed great therapeutic potential of CXCR4+ dNK via recovering the Th2/Th1 bias and reducing embryo resorption rates. The identification of this new dNK cell subset may lay the foundation for understanding NK cell mechanisms in early pregnancy and provide potential prognostic factors for the diagnosis and therapy of RM.

Background: Spatial transcriptomics enables gene expression events to be pinpointed to a specific location in biological tissues. We developed a molecular approach for low-cell and high-fiber Stanford type A aortic dissection and preliminarily explored and visualized the heterogeneity of ascending aortic types and mapping cell-type-specific gene expression to specific anatomical domains.Methods: We collected aortic samples from 15 patients with Stanford type A aortic dissection and a case of ascending aorta was randomly selected followed by 10x Genomics and spatial transcriptomics sequencing. In data processing of normalization, component analysis and dimensionality reduction analysis, different algorithms were compared to establish the pipeline suitable for human aortic tissue.Results: We identified 19,879 genes based on the count level of gene expression at different locations and they were divided into seven groups based on gene expression trends. Major cell that the population may contain are indicated, and we can find different main distribution of different cell types, among which the tearing sites were mainly macrophages and stem cells. The gene expression of these different locations and the cell types they may contain are correlated and discussed in terms of their involvement in immunity, regulation of oxygen homeostasis, regulation of cell structure and basic function.Conclusion: This approach provides a spatially resolved transcriptome− and tissue-wide perspective of the adult human aorta and will allow the application of human fibrous aortic tissues without any effect on genes in different layers with low RNA expression levels. Our findings will pave the way toward both a better understanding of Stanford type A aortic dissection pathogenesis and heterogeneity and the implementation of more effective personalized therapeutic approaches.

Intercropping is used widely by smallholder farmers in developing countries to increase land productivity and profitability. We conducted a maize/peanut intercropping experiment in the 2015 and 2016 growing seasons in Shandong, China. Treatments included sole maize (SM), sole peanut (SP), and an intercrop consisting of four rows of maize and six rows of peanut (IM and IP). The results showed that the intercropping system had yield advantages based on the land equivalent ratio (LER) values of 1.15 and 1.16 in the two years, respectively. Averaged over the two years, the yield of maize in the intercropping was increased by 61.05% compared to that in SM, while the pod yield of peanut was decreased by 31.80% compared to SP. Maize was the superior competitor when intercropped with peanut, and its productivity dominated the yield of the intercropping system in our study. The increased yield was due to a higher kernel number per ear (KNE). Intercropping increased the light transmission ratio (LTR) of the ear layer in the maize canopy, the active photosynthetic duration (APD), and the harvest index (HI) compared to SM. In addition, intercropping promoted the ratio of dry matter accumulation after silking and the distribution of 13C-photosynthates to grain compared to SM. In conclusion, maize/peanut intercropping demonstrated the potential to improve the light condition of maize, achieving enhanced photosynthetic characteristics that improved female spike differentiation, reduced barrenness, and increased KNE. Moreover, dry matter accumulation and 13C-photosynthates distribution to grain of intercropped maize were improved, and a higher grain yield was ultimately obtained.

AIM: To explore the difference of dry eyes between children and adults in terms of symptoms and laboratory examinations.METHODS: Patients in 2018-06/2019-02 with the subjective symptoms of dry eye, and served in Xi'an First Hospital, including 52 children clinic cases(52 eyes)and 55 adult patients cases(55 eyes), all the cases were consulted and examined by slit lamp microscope in anterior segment. Both eyes of tear meniscus height(TMH), the first tear film break-up time(BUTf), the average tear film break-up time(BUTave), lipid layer thickness(LLT)and mesangial gland loss rate were measured by a Keratograph 5M non-invasive ocular surface analyzer.RESULTS: In children, patients' TMH(0.15±0.04mm), BUTf(3.22±1.24s), BUTave(4.27±1.67s), and the rate of meibomian gland loss \〖0.00%(0.00%, 5.03%)\〗 were significantly lower than those in the adult group [0.20±0.05mm, 4.36±1.93s, 5.15±1.49s, 9.90%(5.30%, 18.40%), all Pvs 68.58±21.05nm, P>0.05). Both groups of patients had positive correlation sympathise with BUTf and BUTave, with no correlation between LLT and meibomian gland loss rate in children(rs=-0.23,P=0.10), and adult group patients with negative correlation of LLT and meibomian gland loss rate(rs=-0.28,PCONCLUSION: Children's dry eyes and adult dry eyes in the symptoms, clinical manifestations and examination are different. The main symptom is the increase in the number of blinks. The inspection is mainly characterized by a short BUT. With the decrease of TMH, the rate of meibomian gland loss is relatively insignificant.

Macrophage migration inhibitory factor (MIF) has multiple intrinsic enzymatic activities of the dopachrome/phenylpyruvate tautomerase and thiol protein oxidoreductase, and plays an important role in the development of obesity as a pro-inflammatory cytokine. However, which enzymatic activity of MIF is responsible for regulating in obesity are still unknown. In the present study, we investigated the roles of the tautomerase of MIF in high fat diet (HFD)-induced obesity using MIF tautomerase activity-lacking (MIFP1G/P1G) mice. Our results showed that the serum MIF and the expression of MIF in adipose tissue were increased in HFD-treated mice compared with normal diet fed mice. The bodyweights were significantly reduced in MIFP1G/P1G mice compared with WT mice fed with HFD. The sizes of adipocytes were smaller in MIFP1G/P1G mice compared with WT mice fed with HFD using haematoxylin and eosin (H&E) staining. In addition, the MIFP1G/P1G mice reduced the macrophage infiltration, seen as the decreases of the expression of inflammatory factors such as F4/80, IL-1β, TNFα, MCP1, and IL-6. The glucose tolerance tests (GTT) and insulin tolerance tests (ITT) assays showed that the glucose tolerance and insulin resistance were markedly improved, and the expressions of IRS and PPARγ were upregulated in adipose tissue from MIFP1G/P1G mice fed with HFD. Furthermore, we observed that the expressions of Bax, a pro-apoptotic protein, and the cleaved caspase 3-positive cells in white tissues were decreased and the ratio of Bcl2/Bax was increased in MIFP1G/P1G mice compared with WT mice. Taken together, our results demonstrated that the tautomerase activity-lacking of MIF significantly alleviated the HFD-induced obesity and adipose tissue inflammation, and improved insulin resistance in MIFP1G/P1G mice.

Mesenchymal stem cells (MSCs) have a potently immunosuppressive capacity in both innate and adaptive immune responses. Consequently, MSCs transplantation has emerged as a potential beneficial therapy for autoimmune diseases even though the mechanisms underlying the immunomodulatory activity of MSCs is incompletely understood. Transplanted MSCs from healthy individuals with no known history of autoimmune disease are immunosuppressive in systemic lupus erythematosus (SLE) patients and can ameliorate SLE disease symptoms in those same patients. In contrast, autologous MSCs from SLE patients are not immunosuppressive and do not ameliorate disease symptoms. Recent studies have shown that MSCs from SLE patients are dysfunctional in both proliferation and immunoregulation and phenotypically senescent. The senescent phenotype has been attributed to multiple genes and signaling pathways. In this review, we focus on the possible mechanisms for the defective phenotype and function of MSCs from SLE patients and summarize recent research on MSCs in autoimmune diseases.

Abstract Background Previous studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). Methods One hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot. Results Our data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment. Conclusions These findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.

AIM: To evaluate the morphological changes in anterior segment in Chinese patients with uveal effusion (UE) after the attack of acute primary angle-closure (APAC) using ultrasound biomicroscopy (UBM), and to assess the clinical course and prognosis of the disease. METHODS: In a retrospective case series, 26 eyes in 26 consecutive patients diagnosed with UE after the treatment of intraocular pressure (IOP)-lowering medication for the attack of APAC were enrolled. The unaffected fellow eyes served as controls. The morphological changes were observed by ultrasonography, slit lamp microscopy and gonioscopy. UBM was used to assess the degree and extent of effusion based on the analysis of parameters associated with UE. RESULTS: The mean IOP was 9.2 (SD 2.1) mm Hg at the diagnosis of UE after IOP-lowering medication, while 14.1 (SD, 2.6) mm Hg in the fellow eyes (P=0.000). The anterior chamber depth (ACD) (P=0.000), angle opening distance at 500 μm (AOD500) (P

Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage (HIBD). However, its regulatory role in HIBD remains unclear and was thus examined here using a rat model. To induce HIBD, the left common carotid artery was ligated in neonatal rats, and the rats were subjected to hypoxia for 2 hours. Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine (10 mM in 10 μL) or the autophagy stimulator rapamycin (1 g/kg) 1 hour before artery ligation. Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR1, but by reduced expression of GluR2. Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury, whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury. Additionally, 3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of GluR1 and downregulation of GluR2 in the hippocampus. By contrast, rapamycin further elevated hippocampal GluR1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD. Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats, at least in part, through normalizing GluR1 and GluR2 expression.

Planting at an optimum density and supplying adequate nitrogen (N) to achieve higher yields is a common practice in crop production, especially for maize (Zea mays L.); however, excessive N fertilizer supply in maize production results in reduced N use efficiency (NUE) and severe negative impacts on the environment. This research was conducted to determine the effects of increased plant density and reduced N rate on grain yield, total N uptake, NUE, leaf area index (LAI), intercepted photosynthetically active radiation (IPAR), and resource use efficiency in maize. Field experiments were conducted using a popular maize hybrid Zhengdan 958 (ZD958) under different combinations of plant densities and N rates to determine an effective approach for maize production with high yield and high resource use efficiency. Increasing plant density was clearly able to promote N absorption and LAI during the entire growth stage, which allowed high total N uptake and interception of radiation to achieve high dry matter accumulation (DMA), grain yield, NUE, and radiation use efficiency (RUE). However, with an increase in plant density, the demand of N increased along with grain yield. Increasing N rate can significantly increase the DMA, grain yield, LAI, IPAR, and RUE. However, this increase was non-linear and due to the input of too much N fertilizers, the efficiency of N use at NCK (320 kg ha−1) was low. An appropriate reduction in N rate can therefore lead to higher NUE despite a slight loss in grain production. Taking into account both the need for high grain yield and resource use efficiency, a 30% reduction in N supply, and an increase in plant density of 3 plants m−2, compared to LD (5.25 plants m−2), would lead to an optimal balance between yield and resource use efficiency.

Rigid flow deflectors are usually used on water flow beds to protect engineering structures such as breakwater in coasts and to regulate flow routes in open channels. To reduce its side-effects, i.e., local scour at the toe of deflectors, a flexible flow deflector is proposed, and the corresponding local scour was investigated in this study. A flume experiment was conducted to investigate local scour. To show the advantage of flexible deflectors, a control experimental test was also conducted using a traditional rigid deflector under the same blockage area configuration and the same flow conditions. The flow field near the flexible deflector was also measured to reveal the local flow field. The results show that the bed-scour develops near the toe edges of both flexible and rigid deflectors, but the maximum and averaged scour depths for the flexible deflector are smaller. This advantage of flexible deflector in scour depth is mainly caused by its prone posture, which induces the upward stretching and enlarging horizontally rotating vortex and the upward shifted vertically rotating vortex. The former dissipates more turbulent energy and the latter results in smaller bed shear stress, which lead to smaller scour depth directly. In addition, the up- and down-swaying movement of the flexible deflector can also assistant to dissipate more turbulent energy, thereby damping the intense of the horseshoe vortices and thus weakening scour depth as well. The results of this study provide an elementary understanding on the mechanisms of a flexible flow structure and an alternative deflector-device to reduce scour depth.

Hydrogen sulfide (H2S) has been postulated to be the third gasotransmitter in both animals and plants after nitric oxide (NO) and carbon monoxide (CO). In this review, the physiological roles of H2S in plant growth, development and responses to biotic, and abiotic stresses are summarized. The enzymes which generate H2S are subjected to tight regulation to produce H2S when needed, contributing to delicate responses of H2S to environmental stimuli. H2S occupies a central position in plant sulfur metabolism as it is the link of inorganic sulfur to the first organic sulfur-containing compound cysteine which is the starting point for the synthesis of methionine, coenzyme A, vitamins, etc. In sulfur assimilation, adenosine 5′-phosphosulfate reductase (APR) is the rate-limiting enzyme with the greatest control over the pathway and probably the generation of H2S which is an essential component in this process. APR is an evolutionarily conserved protein among plants, and two conserved domains PAPS_reductase and Thioredoxin are found in APR. Sulfate reduction including the APR-catalyzing step is carried out in chloroplasts. APR, the key enzyme in sulfur assimilation, is mainly regulated at transcription level by transcription factors in response to sulfur availability and environmental stimuli. The cis-acting elements in the promoter region of all the three APR genes in Solanum lycopersicum suggest that multiple factors such as sulfur starvation, cytokinins, CO2, and pathogens may regulate the expression of SlAPRs. In conclusion, as a critical enzyme in regulating sulfur assimilation, APR is probably critical for H2S generation during plants’ response to diverse environmental factors.

[This corrects the article DOI: 10.1371/journal.pone.0180113.].

[This corrects the article DOI: 10.1371/journal.pone.0173277.].

Background: Myocardial infarction is an important cause of mortality after carotid endarterectomy (CEA). Sevoflurane provides myocardial protection to patients undergoing coronary surgery, but whether it also reduces the incidence of myocardial injury in CEA patients is unclear. In this study, we evaluated the cardioprotective effect of low-dose sevoflurane with propofol in patients undergoing CEA. Methods: This was a single-center, prospective, randomized study conducted between November 2011 and December 2013. The study population of 122 patients who underwent CEA were randomly assigned to two groups. Group A (n = 62) received propofol for anesthetic maintenance, and Group B (n = 60) additionally received 0.8% end-tidal sevoflurane. The bispectral index was kept at 40-60. Myocardial injury, defined as cardiac troponin I (cTnI) levels >0.04 ng/ml, was the primary end-point. Levels of cTnI were measured before anesthesia, and at 4, 24, and 72 h after surgery. Perioperative hemodynamic parameters and adverse cardiovascular events after surgery were also recorded. Results: Myocardial injury was detected in 18 patients in Group A and 7 in Group B. The difference was statistically significant (29.0% vs. 11.7%, P = 0.018). The hemodynamic parameters were comparable between the groups, as were adverse cardiovascular events (P = 0.619). Conclusions: Low-dose sevoflurane inhalation along with propofol reduces the incidence of myocardial injury in symptomatic patients after CEA.

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined.

Accumulating evidence shows that hydrogen sulfide (H2S) acts as a multifunctional signaling molecule in plants, whereas the interaction between H2S and ethylene is still unclear. In the present study we investigated the role of H2S in ethylene-promoted banana ripening and senescence by the application of ethylene released from 1.0 g·L-1 ethephon solution or H2S with 1 mM sodium hydrosulfide (NaHS) as the donor or in combination. Fumigation with ethylene was found to accelerate banana ripening and H2S treatment effectively alleviated ethylene-induced banana peel yellowing and fruit softening in parallel with decreased activity of polygalacturonase (PG). Ethylene+H2S treatment also delayed the decreases in chlorophyll and total phenolics, and increased the accumulation of flavonoid, whereas decreased the contents of carotenoid, soluble protein in banana peel and reducing sugar in pulp compared with ethylene treatment alone. Besides, ethylene+H2S treatment suppressed the accumulation of superoxide radicals (·O2-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) which accumulated highly in ethylene-treated banana peels. Furthermore H2S enhanced total antioxidant capacity in ethylene-treated banana peels with the 2,2'-azobis(3-ethylbenz-thiazoline-6-sulfonic acid (ABTS) assay. The result of quantitative real-time PCR showed that the combined treatment of ethylene with H2S down-regulated the expression of ethylene synthesis genes MaACS1, MaACS2 and MaACO1 and pectate lyase MaPL compared with ethylene treatment, while the expression of ethylene receptor genes MaETR, MaERS1 and MaERS2 was enhanced in combination treatment compared with ethylene alone. In all, it can be concluded that H2S alleviates banana fruit ripening and senescence by antagonizing the effect of ethylene through reduction of oxidative stress and inhibition of ethylene signaling pathway.

Aspergillus niger, a saprophytic fungus, is widely distributed in soil, air and cereals, and can cause postharvest diseases in fruit. Polygalacturonase (PG) is one of the main enzymes in fungal pathogens to degrade plant cell wall. To evaluate whether the deletion of an exo-polygalacturonase gene pgxB would influence fungal pathogenicity to fruit, pgxB gene was deleted in Aspergillus niger MA 70.15 (wild type) via homologous recombination. The ΔpgxB mutant showed similar growth behavior compared with the wild type. Pectin medium induced significant higher expression of all pectinase genes in both wild type and ΔpgxB in comparison to potato dextrose agar medium. However, the ΔpgxB mutant was less virulent on apple fruits as the necrosis diameter caused by ΔpgxB mutant was significantly smaller than that of wild type. Results of quantitive-PCR showed that, in the process of infection in apple fruit, gene expressions of polygalacturonase genes pgaI, pgaII, pgaA, pgaC, pgaD and pgaE were enhanced in ΔpgxB mutant in comparison to wild type. These results prove that, despite the increased gene expression of other polygalacturonase genes in ΔpgxB mutant, the lack of pgxB gene significantly reduced the virulence of A. niger on apple fruit, suggesting that pgxB plays an important role in the infection process on the apple fruit.

AIM:To investigate the progression of refractive errors of pupils in Hetian Road primary school of Shanghai Zhabei community and analyze the relationship between refractive errors progression and relative factors. METHODS:All the 6-12 years old in-school pupils in Hetian Road primary school of Shanghai Zhabei community were invited in the study. The participates were examined first-visit in May 2011 and second-visit in May 2012. All the 303 pupils(606 eyes)were investigated the age, height(H), weight(W), uncorrected visual acuity(UCVA), diopter of spherical(DS), diopter of cylinder(DC), spherical equivalent(SE), axial length(AL), and corneal curvature(K). The progression of refractive condition was described and the relevant factors were analyzed.RESULTS:Among 606 eyes, the progression of average SE was -0.45±0.60D and the progression of average AL was 0.32±0.25mm. The progression of SE diopter was positively correlated with the progression of AL(r=0.409, PP=0.004). The youngest pupils with 6-8 years old, had the fastest progression of AL(0.39±0.24mm, PP>0.05). The incidence of poor sight(UCVACONCLUSION:Myopia is the main progression of refractive error in the pupils of Hetian Road primary school in Shanghai Zhabei community. AL and growth development is closely related to the progression of refractive errors.

AIM: To compare therapeutic effect of three different patterns of laser in situ keratomileusis: standard laser in situ keratomileusis(S-LASIK), aspheric ablation laser in situ keratomileusis(A-LASIK), and tissue-saving laser in situ keratomileusis(T-LASIK). METHODS: Retrospective Case Series. From February 2001 to October 2012, 66 patients(112 eyes), who received laser in situ keratomileusis in our hospital and were followed up for more than 6 months, were analyzed retrospectively. The surgery was underwent with 217z excimer laser of Bausch & Lomb and with the 110μm corneal flap made by OUP90 of Moria company. According to diopter, corneal thickness and pupil diameter in dark, different surgical patterns were adopted, and thus the patients were divided into three groups: S-LASIK(n=36), A-LASIK(n=40)and T-LASIK(n=36). The preoperative nocturnal visual satisfaction, nocturnal visual satisfaction in 6 months after the operation, UCVA, BSCVA, spherical equivalent(SE), K value measured by Orbscan II anterior eye segment analysis system, thinnest corneal thickness(TCT)and high-order aberration analysis(C7, C8, C12, RMSh)at 5mm pupil diameter were noted. Changes and relevance of these testing indexes were observed and analyzed preoperatively and postoperatively.RESULTS: According to the research on nocturnal visual satisfaction in 6 months after surgery, A-LASIK group showed better outcome than S-LASIK group and T-LASIK group. In the same period, SE less than ±0.5D in three groups accounted for 96.43%. RMSh, C7 and C12 in three groups all increased postoperatively(P2), 0.72±0.08μm/(D·mm2), 0.59±0.09μm/(D·mm2)respectively(PCONCLUSION: S-LASIK, A-LASIK and T-LASIK can correct myopia and astigmatism effectively. RMSh, C7 and C12 in three groups have all increased postoperatively. The nocturnal visual satisfaction of A-LASIK group is superior to the other two groups, which may be associated with the less change in aberration. Compared with S-LASIK, both A-LASIK and T-LASIK are effective in saving corneal tissue. Ensuring the effect of clinical correction, meanwhile, group T-LASIK reduced the corneal thickness correction to reduce the changes of corneal blomechanics as much as possible.

AIM: To evaluate the refractive status of pupils of Hetian Road primary school in Zhabei community of Shanghai and analyze the relationships between visual acuity and relative factors. METHODS: All the in-school students of Hetian Road primary school in Zhabei community of Shanghai were involved in the study. Four hundred and sixty pupils out of 465 pupils were investigated(The rate was 98.9%). There were 445 pupils with fully data collection. Uncorrected visual acuity(UCVA), age, height(H), weight(W), body mass index(BMI), diopter of spherical(S), diopter of cylinder(C), spherical equivalent(SE), axial length(AL)and corneal curvature(K)were examined. The refractive status was described and the influence of relative factors was analyzed. UCVA measurement uses the standard logarithmic visual acuity chart, recording by decimal number, then transform into LogMar vision for statistical analysis. RESULTS: In total, the average age was 9.49±1.47 year, SE was -0.85±1.82D and UCVA was +0.09±0.28. The prevalence of myopia and astigmatism was 40.9% and 58.9%, respectively. With getting older, the prevalence of myopia increased with the average myopic SE developing significantly(P=0.000). UCVA and AL increased in the same time, SE decreased gradually(PPCONCLUSION: The prevalence of myopia and astigmatism was high in Hetian Road primary school in Zhabei community of Shanghai. Visual acuity is closely related to AL and growth factors.

In the title compound, C16H10O8 or H4bptc, the dihedral angle between the planes of the phenyl rings is 51.90 (4)°. The asymmetric unit contains one half-molecule; complete molecules are generated by a twofold rotation axis. In the crystal, O—H...O and C—H...O hydrogen-bonding generate a two-dimensional supramolecular network. In addition, weak π–π interactions are also observed.