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Abstract 5-Fluorouracil (5-FU) is used as a standard first-line drug for colorectal cancer malignancy (CRC), but it brings a series of side effects such as severe diarrhea and intestinal damage. Our previous study found that a large number of senescent cells increased while 5-Fu induced intestinal damage, and anti-senescence drugs can alleviate its side effects of inflammatory damage. Oleanolic acid (OA) is a common pentacyclic triterpenoid mainly derived from food fungi and medicinal plants, and studies have shown that it mainly possesses hepatoprotective, enzyme-lowering, anti-inflammatory, and anti-tumor effects. But its role in senescence is still unclear. In the present study, we demonstrated for the first time that OA ameliorated 5-Fu-induced human umbilical vein endothelial cells (HUVECs) and human normal intestinal epithelial cells (NCM460) in a 5-Fu-induced cellular senescence model by decreasing the activity of SA-β-gal-positive cells, and the expression of senescence-associated proteins (p16), senescence-associated genes (p53 and p21), and senescence-associated secretory phenotypes (SASPs: IL-1β, IL-6, IL-8, IFN-γ and TNF-α). Meanwhile, in this study, in a BALB/c mouse model, we demonstrated that 5-FU induced intestinal inflammatory response and injury, which was also found to be closely related to the increase of senescent cells, and that OA treatment was effective in ameliorating these adverse phenomena. Furthermore, our in vivo and in vitro studies showed that OA could alleviate senescence by inhibiting mTOR. In colon cancer cell models, OA also enhanced the ability of 5-FU to kill HCT116 cells and SW480 cells. Overall, this study demonstrates for the first time the potential role of OA in counteracting the side effects of 5-FU chemotherapy, providing a new option for the treatment of colorectal cancer to progressively achieve the goal of high efficacy and low toxicity of chemotherapy.

For traditional spent fuel shielding materials, due to physical and chemical defects and cost constraints, they have been unable to meet the needs. Therefore, this paper carries out the first discussion on the application and performance of bismuth in neutron shielding by establishing Monte Carlo simulation on the neutron flux model of shielded spent fuel. Firstly, functional fillers such as bismuth oxide, lead oxide, boron oxide, gadolinium oxide and tungsten oxide are added to the matrices to compare the shielding rates of aluminum alloy matrix and silicone rubber matrix. The shielding rate of silicone rubber mixture is higher than aluminum alloy mixture, reaching more than 56%. The optimal addition proportion of bismuth oxide and lead oxide is 30%, and the neutron radiation protection efficiency reaches 60%. Then, the mass attenuation coefficients of bismuth oxide, lead oxide, boron oxide, gadolinium oxide and tungsten oxide in silicone rubber matrix are simulated with the change of functional fillers proportion and neutron energy. This simulation result shows that the mixture with functional fillers has good shielding performance for low energy neutrons, but poor shielding effect for high energy neutrons. Finally, in order to further evaluate the possibility of replacing lead oxide with bismuth oxide as shielding material, the half-value layers and various properties of bismuth oxide and lead oxide are compared. The results show that the shielding properties of bismuth oxide and lead oxide are basically the same, and the mechanical properties, heat resistance, radiation resistance and environmental protection of bismuth oxide are better than that of lead oxide. Therefore, in the case of neutron source strengths in the range of 0.01–6 MeV and secondary gamma rays produced below 2.5 MeV, bismuth can replace lead in neutron shielding applications.

Abstract Objective Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. Backgrounds Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. Methods Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. Results This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. Conclusion This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Abstract Background Crop-associated microorganisms play a crucial role in soil nutrient cycling, and crop growth, and health. Fine-scale patterns in soil microbial community diversity and composition are commonly regulated by plant species or genotype. Despite extensive reports in different crop or its cultivar effects on the microbial community, it is uncertain how rhizoma peanut (RP, Arachis glabrata Benth.), a perennial warm-season legume forage that is well-adapted in the southern USA, affects soil microbial community across different cultivars. Results This study explored the influence of seven different RP cultivars on the taxonomic composition, diversity, and functional groups of soil fungal communities through a field trial in Marianna, Florida, Southern USA, using next-generation sequencing technique. Our results showed that the taxonomic diversity and composition of the fungal community differed significantly across RP cultivars. Alpha diversity (Shannon, Simpson, and Pielou’s evenness) was significantly higher in Ecoturf but lower in UF_Peace and Florigraze compared to other cultivars (p

As an essential nutrient element for biological growth and metabolism, sulfur is closely interlinked with the carbon and nitrogen cycles, and it is one of the limiting elements for grassland productivity. Here we investigated the spatial distribution of sulfur contents and 34S stable isotope along the North China Transect (NCT), with the aim to explore the shaping role of the aridity index (AI) gradient on sulfur cycling dynamic in arid and semi-arid grasslands. In the area with AI < 0.12, soil sulfur contents and sulfur isotopic compositions (δ34S) showed no correlation with AI, indicating that abiotic processes predominantly govern the sulfur cycle in this area. In the area where 0.12 ≤ AI < 0.32, both sulfur contents and δ34S values increased with rising AI, with microbial-mediated reduction being the primary sulfur cycling process. In the area with 0.32 ≤ AI < 0.60, soil sulfur contents continued to increase with higher AI, but δ34S significantly decreased as AI increased, suggesting plant uptake as the dominant sulfur cycling process in this area. This study demonstrated the significant impact of AI on sulfur dynamics, providing insights into the different drivers of sulfur cycling along the aridity gradient, and offering guidance for developing targeted strategies under global climate change.

IntroductionGrassland-livestock balance is an important principle of sustainable development of grassland livestock production and grassland ecosystem health. Grassland degradation becomes more serious at global scales and especially at the area that is sensitive to climate change and human activities. Decreases in pasture biomass and shifts in plant community composition in degraded grasslands can largely affect grazing behaviors of livestock. Up to date, however, it is unclear that whether livestock behaviors change across spatial and temporal scales and what key factors are to shape observed behavioral patterns of livestock.MethodsHere, yak behaviors including grazing, rumination and walking on the eastern Qinghai-Tibetan Plateau (QTP) were monitored by a continuous visual observation, to investigate temporal and spatial variations of grazing behavior of yaks (Bos grunniens); based on the data from public database in the past 18 years, a meta-analysis was conducted to examine the main factors that affect grazing behaviors and intake of yaks.ResultsWe showed that grazing behaviors of yaks differed significantly within hours, among hours of each day and among days as well as across different observation sites. Intake rate of yaks was higher in the morning than in the afternoon, but walking speed showed an inverse trend compared with intake rate. Resting, altitude, the mean annual precipitation (MAP), the mean annual temperature (MAT), forage ash, yak age and season were the main predictors for yak intake, and forage and yak individual characteristics had direct effects on grazing behaviors and intake of yaks.DiscussionThe findings confirm that grazing behaviors of yaks can vary even at small temporal scales and regional scales, which is closely related to the shift in forage quality and biomass caused by environmental changes. The study suggests that multiple factors can be responsible for the variation in livestock behaviors and shifts in behavioral patterns may consequently lead to positive or negative feedback to grassland ecosystems through plant-animal interactions.

Abstract Background Spinal cord injury (SCI) is one of the most disabling neurological conditions, afflicting thousands of human beings. Edaravone, a well-known reactive oxygen species scavenger, is expanding its new scope in field of SCI. The objective of this systematic review is to determine the neuroprotective effects and discuss the underlying mechanism of edaravone in management of SCI. Methods The systematic review will include the controlled studies evaluating the neurological roles of edaravone on experiment rat models following SCI. The primary outcome will be the 21-point Basso, Beattie, and Bresnahan locomotor rating scale. The secondary outcomes will include the preservation of white matter areas and malondialdehyde levels. Two researchers will independently search PubMed, Embase, Web of Science, Scopus and Cochrane Library from their inception date. Following study selection, data extraction, and assessment of methodological quality in included studies using the SYRCLE’s RoB tool, data from eligible studies will be pooled and analyzed using random-effects models with RevMan 5.3 software. In case of sufficient data, subgroup analyses with respect to species, age, gender, injury characteristics, or administration details will be carried out to explore the factors modifying efficacy of edaravone. For exploring the appropriate dose of edaravone, a network meta-analysis approach will be conducted based on the Bayesian method. Importantly, the proposed mechanisms and changes of related molecules will be also extracted from included studies for comprehensively investigating the mechanisms underlying the neuroprotective effects of edaravone. Discussion In this study, we aim to quantitatively analyze the role of edaravone in locomotor recovery and tissue damage in SCI rat model. The efficacy of edaravone in distinct scenarios will be investigated by subgroup analyses, and we expect to predict the candidate dose that offers a superior treatment effect using network meta-analyses. Moreover, a comprehensive framework regarding the neuroprotective mechanisms behind edaravone will be constructed via a combination of systematic and traditional review. This study will bring implications for future preclinical studies and clinical applications of SCI. Nonetheless, in light of the anticipated limitations in animal experimental design and methodological quality, the results in this review should be interpreted with caution.

Abstract The experimental realization of p-orbital systems is desirable because p-orbital lattices have been proposed theoretically to host strongly correlated electrons that exhibit exotic quantum phases. Here, we synthesize a two-dimensional Fe-coordinated bimolecular metal-organic framework which constitutes a honeycomb lattice of 1,4,5,8,9,12-hexaazatriphenylene molecules and a Kagome lattice of 5,15-di(4-pyridyl)-10,20-diphenylporphyrin molecules on a Au(111) substrate. Density-functional theory calculations show that the framework features multiple well-separated spin-polarized Kagome bands, namely Dirac cone bands and Chern flat bands, near the Fermi level. Using tight-binding modelling, we reveal that these bands are originated from two effects: the low-lying molecular orbitals that exhibit p-orbital characteristics and the honeycomb-Kagome lattice. This study demonstrates that p-orbital Kagome bands can be realized in metal-organic frameworks by using molecules with molecular orbitals of p-orbital like symmetry.

Soybean yield has traditionally been increased through high planting density, but investigating plant height and petiole traits to select for compact architecture, lodging resistance, and high yield varieties is an underexplored option for further improving yield. We compared the relationships between yield-related traits, lodging resistance, and petiole-associated phenotypes in the short petiole germplasm M657 with three control accessions during 2017–2018 in four locations in the Huang–Huai region, China. The results showed that M657 exhibited stable and high tolerance to high planting density and resistance to lodging, especially at the highest density (8×105 plants ha−1). The regression analysis indicated that a shorter petiole length was significantly associated with increased lodging resistance. The yield analysis showed that M657 achieved higher yields under higher densities, especially in the northern part of the Huang–Huai region. Among the varieties, there were markedly different responses to intra- and inter-row spacing designs with respect to both lodging and yield that were related to location and density. Lodging was positively correlated with planting density, plant height, petiole length, and number of effective branches, but negatively correlated with stem diameter, seed number per plant, and seed weight per plant. The yield of soybean was increased by appropriately increasing the planting density on the basis of the current soybean varieties in the Huang–Huai region. This study provides a valuable new germplasm resource for the introgression of compact architecture traits that are amenable to providing a high yield in high density planting systems, and it establishes a high-yield model of soybean in the Huang–Huai region.

This study aimed to evaluate the ability of rete testis thickness (RTT) and testicular shear wave elastography (SWE) to differentiate obstructive azoospermia (OA) from nonobstructive azoospermia (NOA). We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital (Shanghai, China) between August 2019 and October 2021. The testicular volume (TV), SWE, and RTT were compared among patients with OA and NOA and healthy controls. The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve. The TV, SWE, and RTT in OA differed significantly from those in NOA (all P ≤ 0.001) but were similar to those in healthy controls. Males with OA and NOA were similar at TVs of 9–11 cm3 (P = 0.838), with sensitivity, specificity, Youden index, and area under the curve of 50.0%, 84.2%, 0.34, and 0.662 (95% confidence interval [CI]: 0.502–0.799), respectively, for SWE cut-off of 3.1 kPa; and 94.1%, 79.2%, 0.74, and 0.904 (95% CI: 0.811–0.996), respectively, for RTT cut-off of 1.6 mm. The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range. In conclusion, ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA, particularly in the TV overlap range.

AIM: To compare the efficacy and safety of dexamethasone intravitreal implant combined with anti-VEGF drug and anti-VEGF drug monotherapy in the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A total of 133 patients(133 eyes)diagnosed with central retinal vein occlusion(CRVO)or branch vein occlusion(BRVO)secondary to macular edema in the Xiamen Eye Center of Xiamen University from June 2019 to December 2020, including 48 patients with CRVO-ME and 85 patients with BRVO-ME were analyzed. All patients were randomly assigned to monotherapy or combination therapy. The monotherapy group(66 eyes)received a monthly injection of conbercept for consecutive 3mo, followed by monthly follow-up visits; The combination therapy group(67 eyes)received once intravitreal dexamethasone implantation, and conbercept was injected once 1wk later, followed by monthly follow-up visits.All patients in the two treatment groups were evaluated at baseline and every subsequent visit until 6mo after treatment with the best corrected visual acuity(BCVA), macular central retinal thickness(CRT), and injection times of conbercept and ocular and systemic adverse events associated with intravitreal injection therapy were recorded.RESULTS: At 1, 2, 3 and 6mo after treatment, the BCVA and CRT in both groups were significantly improved than before.But there was no significant difference in the improvement of BCVA and CRT(P >0.05). From the initial intravitreal injection to 6mo, the injection times of the monotherapy group and the combination therapy group were 3.56±0.12 and 2.96±0.17 times, respectively. The injection times of the combination therapy group were significantly lower than those of the monotherapy group(P=0.004). Both the incidences of intraocular hypertension and cataract in the combination therapy group were higher than those in the anti-VEGF monotherapy group.CONCLUSION: dexamethasone intravitreal implant combined with anti-VEGF drugs is an effective method for the treatment of RVO-ME, with significantly improved visual acuity and significantly lower CRT; The combined treatment regimen can reduce the times of injections and achieve similar results to anti-VEGF drug monotherapy. However, monitoring of intraocular pressure and cataract progression is required.

AIM: To compare and observe the efficacy of 25G+ and 27G+ minimally invasive vitrectomy(MIVS)in the treatment of vitreoretinal diseases.METHODS: A retrospective case-control study, 76 patients(76 eyes)with various vitreoretinal diseases treated in our hospital from December 2018 to January 2020 were selected and randomly divided into 25G+ group and 27G+ group underwent vitrectomy, and the operation time of the two groups of patients, as well as the changes of ETDRS visual acuity, intraocular pressure, and conjunctival edema 1d before surgery, 1d after surgery, and 1, 4, 12, and 24wk after surgery were compared and analyzed.RESULTS: Compared with the 25G+ group, the 27G+ group had a longer vitrectomy time(27.17±5.95 vs 26.71±5.93min)and the total operation time was shorter than that of the 25G+ group(28.26±6.88 vs 30.37±6.68 min), but there was no significant difference between the two groups(t=0.322, P=0.748; t=-1.353, P=0.180). After vitrectomy, the visual acuity of the two groups was significantly improved compared with that before operation, but there was no significant difference between the two groups(P>0.05). Compared with the 25G+ group, the intraocular pressure fluctuation range of the 27G+ group at 1d(12.58±2.44 vs 10.56±3.21mmHg, t=2.943, P=0.004)and 1wk(13.48±2.85 vs 12.89±2.01mmHg, t=1.460, P=0.031)after the operation was low. Within 1wk after the operation, 7 eyes of transient hypotony occurred in the 25G+ group, but no hypotony occurred in the 27G+ group, indicating that the 27G+ MIVS can better stabilize postoperative intraocular pressure.CONCLUSION: 27G+ MIVS and 25G+ MIVS are safe and effective in the treatment of vitreoretinal diseases. Compared with 25G+ MIVS, 27G+ MIVS can better stabilize intraocular pressure and reduce the occurrence of complications caused by postoperative hypotony.

Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.

Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella (MMAF), which cause severe asthenozoospermia and lead to male infertility, while the causes of approximately 50% of MMAF cases remain unclear. To reveal the genetic causes of MMAF in an infertile patient, whole-exome sequencing was performed to screen for pathogenic genes, and electron microscope was used to reveal the sperm flagellar ultrastructure. A novel heterozygous missense mutation in the outer dense fiber protein 2 (ODF2) gene was detected, which was inherited from the patient's mother and predicted to be potentially damaging. Transmission electron microscopy revealed that the outer dense fibers were defective in the patient's sperm tail, which was similar to that of the reported heterozygous Odf2 mutation mouse. Immunostaining of ODF2 showed severe ODF2 expression defects in the patient's sperm. Therefore, it was concluded that the heterozygous mutation in ODF2 caused MMAF in this case. To evaluate the possibility of assisted reproductive technology (ART) treatment for this patient, intracytoplasmic sperm injection (ICSI) was performed, with the help of a hypo-osmotic swelling test and laser-assisted immotile sperm selection (LAISS) for available sperm screening, and artificial oocyte activation with ionomycin was applied to improve the fertilization rate. Four ICSI cycles were performed, and live birth was achieved in the LAISS-applied cycle, suggesting that LAISS would be valuable in ART treatment for MMAF.

PM2.5 is an important environmental problem threatening human health at present, which poses serious harm to human body after inhalation. J. cannabifolia is a traditional Chinese medicine which exhibits anti-inflammatory effect. This study aimed to investigate the inhibitory effect of main phenolic acid components of J. cannabifolia on inflammation caused by PM2.5. Effect of PM2.5 on cell activity and apoptosis were determined by MTT, flow cytometry and calcein AM/PI staining. PHBA, PHPAA, and mixture of PHBA and PHPAA of different concentrations were given to RAW264.7 cells pretreated with PM2.5. The effect of drugs on cellular inflammatory factors was detected by ELISA. The expressions of TLRs related signal pathway at protein and gene levels were detected by western blot and qRT-PCR. The results showed that PM2.5 had no effect on cell activity and apoptosis within the determined concentration range. PHBA and PHPAA could markly inhibit the level of IL-1β, IL-6, and TNF-α in RAW264.7 cells. Furthermore, the expressions of TLR2, TLR4, MyD88, IRAK1, TRAF6, TAK1, IKKβ, and NF-κB induced by PM2.5 were markedly inhibited by PHBA and PHPAA at protein and gene levels. This study demonstrated that PHBA and PHPAA could attenuated inflammation caused by PM2.5 through suppressing TLRs related signal pathway.

Abstract Background Evidence suggests gut microbiome is associated with diabetes. However, it’s unclear whether the association remains in non-diabetic participants. A Chinese monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, was conducted to explore the potential association. Methods Nine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites. Results The participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm2 (152.2 ± 31.6). There was no significant difference of VAT between the twin groups (153.6 ± 30.4 cm2 vs. 150.8 ± 29.5 cm2, p = 0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p ≥ 0.056), whereas HbA1c level of group a is significantly higher than group b (5.8 ± 0.3% vs. 5.6 ± 0.2%, p = 0.008). The number and richness of OTUs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle. Conclusions Gut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.

ABSTRACT Global changes will result in altered precipitation patterns, among which the increasing frequency of drought events has the highest deleterious potential for agriculture. Soil microbes have shown some promise to help crops adapt to drought events, but it is uncertain how crop-associated microorganisms will respond to altered precipitation patterns. To investigate this matter, we conducted a field experiment where we seeded two wheat cultivars (one resistant to water stress and the other sensitive) that were subjected to four precipitation exclusion (PE) regimes (0%, 25%, 50%, and 75% exclusion). These cultivars were sampled seven times (every 2 weeks, from May to August) within one growing season to investigate short-term microbiome responses to altered precipitation regimes and seasonality using 16S rRNA gene and internal transcribed spacer (ITS) region amplicon sequencing. One of the most striking features of the data set was the dramatic shift in microbial community diversity, structure, and composition together with a doubling of the relative abundance of the archaeal ammonia oxidizer genus Nitrososphaera following an important drying-rewetting event. Comparatively small but significant effects of PE and wheat cultivar on microbial community diversity, composition, and structure were observed. Taken together, our results demonstrate an uneven response of microbial taxa to decreasing soil water content, which was dwarfed by drying-rewetting events, to which soil bacteria and archaea were more sensitive than fungi. Importantly, our study showed that an increase in drying-rewetting cycles will cause larger shifts in soil microbial communities than a decrease in total precipitation, suggesting that under climate changes, the distribution of precipitation will be more important than small variations in the total quantity of precipitation. IMPORTANCE Climate change will have a profound effect on the precipitation patterns of global terrestrial ecosystems. Seasonal and interannual uneven distributions of precipitation will lead to increasing frequencies and intensities of extreme drought and rainfall events, which will affect crop productivity and nutrient contents in various agroecosystems. However, we still lack knowledge about the responses of soil microbial communities to reduced precipitation and drying-rewetting events in agroecosystems. Our results demonstrated an uneven response of the soil microbiome and a dramatic shift in microbial community diversity and structure to a significant drying-rewetting event with a large increase in the relative abundance of archaeal ammonia oxidizers. These findings highlight the larger importance of rewetting of dry soils on microbial communities, as compared to decreased precipitation, with potential for changes in the soil nitrogen cycling.

The black soldier fly larvae (BSFL) (Hermetia illucens) are a good candidate for poultry and livestock manure treatment. The harvested insect bodies and feces can be used as animal feed and organic fertilizer. However, heavy metals have a negative impact on the transformation process of the manure by BSFL. Here we evaluated the effects of Cd, Cr and As in pig manure on the growth of BSFL, as well as the mobility and changes in speciation of the metals during the transformation process. The results showed that As significantly reduced the weight of BSFL, but Cr and Cd had no significant effects on BSFL growth. The bioaccumulation factors (BAFs) at various concentrations of Cd (2.8–3.7) were significantly higher than those of Cr (0.44–0.62) and As (0.43–0.45). The heavy metals in pig manure were mainly transferred to BSFL feces, and the distribution percentages of Cd, Cr and As in the BSFL feces were 52.6–62.0%, 90.3–94.2% and 93.0–93.3%, respectively. Cd concentrations in BSFL feces were significantly lower than those in the pig manure, while there were no significant differences in the concentrations of Cr and As between BSFL feces and pig manure (except for the treatment with the addition of 150 mg Cr kg−1). The metal speciation (weak acid soluble, reducible, oxidizable and residual fractions) in BSFL feces obviously changed when compared with pig manure. In BSFL feces, the reducible proportion of Cr decreased while the oxidizable proportion increased. Cd mainly existed in the weak acid soluble and reducible states in pig manure and BSFL feces. For As, the proportions of weak acid soluble and reducible states decreased in BSFL feces. After the BSFL transformation process, the bioavailable fraction of Cr decreased by 17.3–23.1%, but those of Cd and As did not change significantly, except for As in the CK group. These findings contribute to our understanding of the roles of BSFL during the biotransformation process of livestock manure as well as the safe utilization of transformed products.

Developing effective therapies and medicines to conquer nonalcoholic steatohepatitis (NASH) is of great significance for public health and is faced with a major challenge. The activation of the thyroid hormone receptor agonist THRβ could be regulated by target drugs that has brought huge potential to the treatment of NASH. In this work, pyridazinone compound YWS01125 was synthesized for the first time. In this study, an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for YWS01125 determination was established, and the pharmacokinetics of YWS01125 was evaluated. The half-life values (t1/2)of three different doses of YWS01125 was 189.12 ± 95.27, 152.64 ± 37.98, and 181.95 ± 64.25 min, respectively, and the tissue distribution studies demonstrated that YWS01125 was quickly distributed to various tissues. With successful application in the pharmacokinetics study of YWS01125, the UPLC-MS/MS method has shown characteristics of high sensitivity, rapidity, and good selectivity.

In clinical practice, arsenic trioxide can be used to treat a subset of R/R CML patients, but resistance tends to reappear quickly. We designed an experiment to study arsenic trioxide resistance in K-562 cells. Previously, we identified the UNC13B gene as potentially responsible for arsenic trioxide resistance in K-562 cells via gene chip screening followed by high-content screening. We aimed to investigate the role and mechanism of the UNC13B gene in K-562 cells, an arsenic trioxide-resistant chronic myeloid leukemia cell line. In vitro lentiviral vector-mediated UNC13B siRNA transfection was performed on K-562 cells. The roles of UNC13B in cell proliferation, apoptosis and cell cycle pathways, and colony formation were analyzed by CCK-8 assay, fluorescence-activated cell sorting, and soft agar culture, respectively. Gene chip screening was used to define the possible downstream pathways of UNC13B. Western blot was performed to further validate the possible genes mediated by UNC13B for arsenic trioxide resistance in patients with chronic myeloid leukemia. UNC13B downregulation significantly inhibited growth, promoted apoptosis, decreased colony formation, reduced the duration of the G1 phase, and increased the duration of the S phase of K-562 cells. Western blot results confirmed that UNC13B may modulate the apoptosis and proliferation of arsenic trioxide-resistant chronic myeloid leukemia cells through the mediation of MAP3K7, CDK4, and PINK1. UNC13B is a potential therapeutic target for patients with arsenic trioxide-resistant chronic myeloid leukemia.

Serpula similis is an interesting member of Hymenomycetes in association with bamboo clumps. However, the functions of Serpula similis on cellular senescence are not clear yet. In this study, the protective effect of fermentation broth of Serpula similis (FeBrSS) on cellular senescence-induced by oxidative stress and the potential mechanism was studied. The stress-induced premature senescence model was established by hydrogen peroxide, and model cells were subjected to the intervention with FeBrSS. As a result, we found that FeBrSS administration certainly repressed activity of senescence associated β-Galactosidase and expression of senescence-associated genes. Interestingly, the effects of FeBrSS are related to the restoration of impaired autophagy via activation of AMP-activated protein kinase (AMPK) other than via mTORC1 pathway. Together, our study demonstrated for the first time that FeBrSS have the effects of inhibiting senescence via autophagy restoration which occurs due to activation of AMPK pathway, and therefore, supported that autophagy plays a critical role in anti-aging. Our findings expanded the list of fermentation broth of fungus of significance and may provide new evidence or strategies for developing new drugs for anti-aging.

Rhizosphere colonization is a key requirement for the application of plant growth-promoting rhizobacteria (PGPR) as a biofertilizer. Signaling molecules are often exchanged between PGPR and plants, and genes in plants may respond to the action of PGPR. Here, the luciferase luxAB gene was electrotransformed into Pseudomonas sp. strain TK35, a PGPR with an affinity for tobacco, and the labelled TK35 (TK35-L) was used to monitor colonization dynamics in the tobacco rhizosphere and evaluate the effects of colonization on tobacco growth and root development. The transcript levels of the hydroxyproline-rich glycoprotein HRGPnt3 gene, a lateral root induction indicator, in tobacco roots were examined by qPCR. The results showed that TK35-L could survive for long periods in the tobacco rhizosphere and colonize new spaces in the tobacco rhizosphere following tobacco root extension, exhibiting significant increases in root development, seedling growth and potassium accumulation in tobacco plants. The upregulation of HRGPnt3 transcription in the inoculated tobacco suggested that TK35-L can promote tobacco root development by upregulating the transcript levels of the HRGPnt3 gene, which promotes tobacco seedling growth. These findings lay a foundation for future studies on the molecular mechanism underlying the plant growth-promoting activities of PGPR. Furthermore, this work provided an ideal potential strain for biofertilizer production.

Abstract Clinicians have been faced with the challenge of differentiating between severe acute respiratory syndrome associated coronavirus 2 (SARS‐CoV‐2) infected pneumonia (NCP) and influenza A infected pneumonia (IAP), a seasonal disease that coincided with the outbreak. We aim to develop a machine‐learning algorithm based on radiomics to distinguish NCP from IAP by texture analysis based on computed tomography (CT) imaging. Forty‐one NCP and 37 IAP patients admitted from January to February 6, 2019 admitted to two hospitals in Wenzhou, China. All patients had undergone chest CT examination and blood routine tests prior to receiving medical treatment. NCP was diagnosed by real‐time RT‐PCR assays. Eight of 56 radiomic features extracted by LIFEx were selected by least absolute shrinkage and selection operator regression to develop a radiomics score and subsequently constructed into a nomogram to predict NCP with area under the operating characteristics curve of 0.87 (95% confidence interval: 0.77‐0.93). The nomogram also showed excellent calibration with Hosmer‐Lemeshow test yielding a nonsignificant statistic (P = .904). The novel nomogram may efficiently distinguish between NCP and IAP patients. The nomogram may be incorporated to existing diagnostic algorithm to effectively stratify suspected patients for SARS‐CoV‐2 pneumonia.

The mechanisms regulating regeneration of the earthworm are unclear. Here, the authors use genomic and transcriptomic analysis of the earthworm Eisenia andrei together with Hi-C analysis to identify genes involved and show activation of LINE2 transposable elements on regeneration.

An experimental study was undertaken to study the tube-side evaporation heat transfer characteristics of enhanced tubes and compare their performance with that of smooth tubes. These experiments were conducted in order to determine how R410a evaporates inside smooth and enhanced tubes; for a saturation temperature of 279.15 K; with mass flux values that ranged from 50 to 250 kg/(m2·s); for an inlet quality of 0.2 and outlet quality of 0.8. Enhanced tubes evaluated include herringbone (HB) and helix (HX) designs with microgrooves, composite herringbone dimple (HB/D), composite herringbone hydrophobic (HB/HY), and composite EHT (multiple enhancement character) tubes. Experimental results show that the evaporation heat-transfer coefficient in the Cu-EHTb tube was the highest; its performance was closely related to the increased number of nucleation points that are found inside the tube; however, the performance of the SS-EHT-HB/D was not significantly higher than that of a smooth tube. The best overall capacity for evaporative heat transfer is shown in the SS-EHT-HB/HY and SS-EHT-HX tubes; the SS-EHT-HB/D, Cu-EHTa, and Cu-EHTb tubes had the worst overall capacity among all the tested tubes. Additionally, it was determined that previously reported smooth tube models to determine the evaporation heat transfer coefficient can accurately predict the heat transfer inside a smooth tube. However, when trying to utilize smooth tube models for enhanced tubes, the deviation between experimentally determined heat transfer coefficient (HTC) values and those predicted when using smooth tube models to predict enhanced tube results is ±30%; therefore, smooth tube models are not applicable for use with enhanced tubes. Smooth tube models were modified, and after correction, the deviation between experimentally determined heat transfer coefficient (HTC) values and those predicted when using the modified model for use with enhanced tubes is ±10%. Finally, the effect of the thermal resistance of the tube wall on the overall heat transfer coefficient of a stainless steel-enhanced tube is significant and cannot be overlooked.

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mβCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

Abstract There is a growing awareness of the importance of soil microorganisms in agricultural management practices. Currently, much less is known about whether different crop cultivar has an effect on the taxonomic structure and diversity, and specific functions of soil bacterial communities. Here, we examined the changes of the diversity and composition and enzyme‐encoding nitrogenase genes in a long‐term field experiment with seven different rhizoma peanut cultivars in southeastern USA, coupling high‐throughput 16S rRNA gene sequencing and the sequence‐based function prediction with Tax4Fun. Of the 32 phyla detected (Proteobacteria class), 13 were dominant: Acidobacteria, Alphaproteobacteria, Actinobacteria, Betaproteobacteria, Bacteroidetes, Verrucomicrobia, Gammaproteobacteria, Deltaproteobacteria, Gemmatimonadetes, Firmicutes, Nitrospirae, Chloroflexi, and Planctomycetes (relative abundance >1%). We found no evidence that the diversity and composition of bacterial communities were significantly different among different cultivars, but the abundance of some dominant bacterial groups that have N‐fixation potentials (at broad or fine taxonomic level) and predicted abundances of some enzyme‐encoding nitrogenase genes showed significant across‐cultivar differences. The nitrogenase genes were notably abundant in Florigraze and Latitude soils while remarkably lower in Arbook and UF_TITO soils when compared with other cultivars, indicating different nitrogen fixation potentials among different cultivars. The findings also suggest that the abundance of certain bacterial taxa and the specific function bacteria perform in ecosystems can have an inherent association. Our study is helpful to understand how microbiological responses and feedback to different plant genotypes through the variation in structure and function of their communities in the rhizosphere.

Fungal endophytes have been extensively found in most terrestrial plants. This type of plant–microorganism symbiosis generates many benefits for plant growth by promoting nutrient availability, uptake, and resistance to environmental disease or stress. Recent studies have reported that fungal endophytes have a potential impact on plant litter decomposition, but the mechanisms behind its effect are not well understood. We proposed a hypothesis that the impacts of fungal endophytes on litter decomposition are not only due to a shift in the symbiont-induced litter quality but a shift in soil microenvironment. To test this hypothesis, we set-up a field trial by planting three locally dominant grass species (wild barley, drunken horse grass, and perennial ryegrass) with Epichloë endophyte-infected (E+) and -free (E−) status, respectively. The aboveground litter and bulk soil from each plant species were collected. The litter quality and the soil biotic and abiotic parameters were analyzed to identify their changes across E+ and E− status and plant species. While Epichloë endophyte status mainly caused a significant shift in soil microenvironment, plant species had a dominant effect on litter quality. Available nitrogen (N) and phosphorus (P) as well as soil organic carbon and microbial biomass in most soils with planting E+ plants increased by 17.19%, 14.28%, 23.82%, and 11.54%, respectively, in comparison to soils with planting E− plants. Our results confirm that fungal endophytes have more of an influence on the soil microenvironment than the aboveground litter quality, providing a partial explanation of the home-field advantage of litter decomposition.

Red raspberry (Rubus idaeus L.) is an edible fruit-producing species belonging to the Rosaceae family. In our search for potential agents for treating Alzheimer’s disease in this functional food, we decided to investigate the chemical constituents of red raspberry. Four pairs of enantiomeric 8-O-4′-type neolignans (1a/1b–4a/4b), including three new compounds (1a/1b and 2a), were identified from the fruit of red raspberry. Their chemical structures were determined by spectroscopic data analyses, and all these isolated compounds were evaluated for their inhibition of self-induced Aβ aggregation, and 1b, 2a and 2b exhibited significant Aβ aggregation inhibition ability. The results of the docking study of enantiomeric compounds 1a/1b and 3a/3b were consistent with the results of the thioflavin-T assay, and were used to further interpret the effects of a variety of stereochemical configurations on the Aβ aggregation assay. Moreover, their neuroprotective activities were also evaluated.

Abstract Neutrophil recruitment to injured tissue appears to be an evolutionarily conserved strategy for organisms to fight against exogenous insults. Recent studies have shown rhythmic migration of neutrophils and several factors, including melatonin, have been implicated in regulating this rhythmic migration. The mechanisms underlying how endogenous melatonin regulates rhythmic neutrophils migration, however, are unclear. Here we generated a zebrafish annat2 mutant that lacks endogenous melatonin and, subsequently, a Tg(lyz:EGFP);aanat2 −/− transgenic line that allows for monitoring neutrophils migration visually in live zebrafish. We observed that migrating neutrophils are significantly reduced in aanat2 −/− mutant zebrafish under a light/dark condition, and the disrupted migrating rhythmicity of neutrophils in aanat2 −/− zebrafish is independent of the circadian clock. Further, we also found that endogenous melatonin enhances neutrophils migration likely by inducing the expression of cytokines such as interleukin-8 and interleukin-1β. Together, our findings provide evidence that endogenous melatonin promotes rhythmic migration of neutrophils through cytokines in zebrafish.

Abstract Background The application of laminar screws is an alternative fixation for the first thoracic vertebra (T1). This paper is to determine the anatomical characteristics for adequate laminar screw fixation, and present a modified method of sagittal reconstruction of T1 to provide more accurate measurements. Methods Computed tomography (CT) images of 62 patients (32 males, 30 females) were used for the analysis. The following parameters of the T-1 lamina were measured using Mimics software: lamina length, axis angle, minimal outer cortical width, cancellous width, minimal outer cortical height, cancellous height, and spinous process height. Right or left modified sagittal reconstructions (parallel to right or left screws) were innovatively used for measurement. Results There were no significant differences between the left and right sides for each measurement performed (P > 0.05), but significant differences were detected between males and females (P

The growth periods (GPs, from planting/emergence to reproductive stage 8 (R8) of soybean cultivars vary in different ecological regions, especially in China with a very complex soybean cropping system. In this study, a 3-yr experimental study was undertaken in three geographical locations of China from 2008 to 2010, including the Northeast (40.66–45.85°N), Huang-Huai (34.75–38.04°N) and southern (22.82–30.60°N) eco-regions with about 250 accessions in each region to clarify the classification of maturity group (MG) and identify the cultivars with stable GP to increase the knowledge about the GP distribution of soybean cultivars in China. GPs of soybean cultivars in different eco-regions were significant different with a gradual decrease from 115–125 d in the Northeast part to the 85–100 d in the southern part of China. The geographical location was the major factor for GP of cultivars from the Northeast, while the year of planting was the major factor affecting the stability of GPs in Huang-Huai summer and southern summer soybean. AMMI2 (additive main effects and multiplicative interaction)-Biplot analysis showed that the GPs of soybean cultivars from the Northeast eco-region have a comparatively satisfactory environmental stability. Moreover, soybean cultivars with moderate GP/MG and stable environment adaptability in different eco-regions were identified based on the linear regression and AMMI analysis, which was important for the accurate classification of soybean MGs in future. Taken together, our results reflected the genetic diversity, geographical distribution and environmental stability of the Chinese soybean GP trait. Soybean cultivars with stable GP for various Chinese eco-regions would be beneficial for Chinese soybean genetic improvement, varietal introduction, exchange, and soybean breeding program for wide adaptability.

Background and Objective: Anxiety/depression and tuberculosis are global public health problems. The incidence of psychiatric morbidities is high among tuberculosis patients. However, little is known about the prevalence of anxiety and depression among Chinese pulmonary tuberculosis (PTB) patients, especially those with tracheobronchial tuberculosis (TBTB). The goal of the present study was to explore the prevalence of and associated factors of anxiety and depressive symptoms among PTB patients with and without TBTB.Methods: A cross-sectional survey of PTB patients from three hospitals in Liaoning, China, was conducted using a structured questionnaire. Depression and anxiety were evaluated by using the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9 (PHQ-9).Results: According to HADS and PHQ-9, 17.73 and 18.13% of 1252 PTB patients, respectively, had significant depressive symptoms and based on HADS scale, 18.37% had significant anxiety symptoms. Approximately 70% of patients with probable depression also had significant anxiety symptoms, and vice versa, and 69.6% patients with anxiety symptoms were also diagnosed with probable depression in our study population. Dyspnea and TBTB were significantly associated with depressive symptoms. Other depressive symptoms-related factors included age, divorce, abnormal body mass index (BMI), and low income. Patients with lower incomes, symptoms of dyspnea, or a combination of ≥3 clinical symptoms had an increased risk of anxiety symptoms, while patients with occasional or frequent alcohol consumption had a reduced risk of anxiety symptoms.Conclusion: Depressive and anxiety symptoms are common among PTB patients, especially those with TBTB. Screening for depression and anxiety is essential for identifying patients who require further psychosocial assessment and support.

Objective: Idiopathic pulmonary fibrosis is an irreversible and progressive fibrotic lung disease that leads to declines in pulmonary function and, eventually, respiratory failure and has no effective treatment. Gly-His-Lys (GHK) is a tripeptide involved in the processes of tissue regeneration and wound healing and has significant inhibitory effects on transforming growth factor (TGF)-β1 secretion. The effect of GHK on fibrogenesis in pulmonary fibrosis and the exact underlying mechanism have not been studied previously. Thus, this study investigated the effects of GHK on bleomycin (BLM)-induced fibrosis and identified the pathway that is potentially responsible for these effects.Methods: Intratracheal injections of 3 mg/kg BLM were administered to induce pulmonary fibrosis in C57BL/6 mice. GHK was administered intraperitoneally at doses of 2.6, 26, and 260 μg/ml/day every other day from the 4th to the 21st day after BLM instillation. Three weeks after BLM instillation, pulmonary injury and pulmonary fibrosis was evaluated by the hematoxylin-eosin (HE) and Masson’s trichrome (MT) staining. Chronic inflammation index was used for the histological assessments by two pathologists blindly to each other. Tumor necrosis factor (TNF)-α and IL-6 levels in BALF and myeloperoxidase (MPO) activity in lung extracts were measured. For the pulmonary fibrosis evaluation, the fibrosis index calculated based on MT staining, collagen deposition and active TGF-β1 expression detected by ELISA, and the expression of TGF-β1, α-smooth muscle actin (SMA), fibronectin, MMP-9, and TIMP-1 by western blotting. The epithelial mesenchymal transition index, E-cadherin, and vimentin was also detected by western blot. The statistical analysis was performed by one-way ANOVA and the comparison between different groups were performed.Results: Treatment with GHK at all three doses reduced inflammatory cell infiltration and interstitial thickness and attenuated BLM-induced pulmonary fibrosis in mice. GHK treatment significantly improved collagen deposition, and MMP-9/TIMP-1 imbalances in lung tissue and also reduced TNF-α, IL-6 expression in bronchoalveolar lavage fluid (BALF) and MPO in lung extracts. Furthermore, GHK reversed BLM-induced increases in TGF-β1, p-Smad2, p-Smad-3 and insulin-like growth factor-1 (IGF-1) expression.Conclusion: GHK inhibits BLM-induced fibrosis progression, the inflammatory response and EMT via the TGF-β1/Smad 2/3 and IGF-1 pathway. Thus, GHK may be a potential treatment for pulmonary fibrosis.

AIM: To compare the safety and efficacy of intravitreal injection with ranibizumab combined with grid laser photocoagulation for the treatment of macular edema secondary to branch retinal vein occlusion(BRVO).METHODS: Thirty patients(30 eyes)with BRVO were randomized into two groups: Group 1(14 eyes)received grid laser photocoagulation(GLP)treatment alone, Group 2(16 eyes)received three loading doses 0.05mL/(0.5mg)of intravitreal injection with ranibizumab at monthly interval(i.e. 0, 1 month and 2 months)plus standard laser treatment 7d after the 1st injection. During the 6 months of follow-up, observation was made on the changes of the best-corrected visual acuity(BCVA)and central macular thickness(CMT)by OCT.RESULTS: After 6 months follow-up, the patients' BCVA in two groups were both improved with the combined treatment group better than the simple GLP group(PPCONCLUSION: The effect of the combined treatment is better than that of the simple GLP treatment. Intravitreal injection with ranibizumab combined with grid laser photocoagulation for the treatment of macular edema secondary to branch retinal vein occlusion is effective and safe.

China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells. Suppression of SNAI2 suffices to up-regulate several cancer stem genes. Although unrelated to the metastatic ability, SNAI2 inhibition does increase the efflux of Hoechst 33342 and enhance multidrug resistance in vitro and in vivo. In agreement with this data, we demonstrate for the first time that decreasing SNAI2 level can transcriptionally upregulate several ATP binding cassette (ABC) transporter genes such as ABCB1. Moreover, ABC transporters' inhibitor verapamil can rescue the multidrug resistance induced by SNAI2 inhibition. Our results implicate that SNAI2 behaves as a tumor suppressor by inhibiting multidrug resistance via suppressing ABC transporter genes in HCC cells.

AIM: To observe the effect of the treatment to the perfluorodecalin residue on macular subretinal by internal limiting membrane(ILM)peeling combined with 38G casing needle.METHODS: Twenty-nine cases(29 eyes)of retinal reattachment and with perfluorodecalin residual on the macular subretinal, selected in Xiamen Eye Center from January 2008 to October 2013, were divided into group A(14 cases, 14 eyes)and group B(15 cases, 15 eyes)randomly. In group A, after removal of silicone oil, perfluorodecalin liquids at the macular subretinal directly were aspirated by 38G casing needle. In group B, after removal of silicone oil, ILM was dyed and peeled completely to the range of 4PD approximately. Then the perfluorodecalin liquids at the macular subretinal were aspirated by 38G casing needle. All cases of both groups were filled with filtered air. After 1wk, the case with macular hole found by OCT was exchanged by air-fluid and filled with 16% C3F8. The best corrected visual acuity(BCVA)of two groups of patients was observed after 4, 8, 24wk. OCT was reviewed to observe whether there were perfluorodecalin residue on the macular subretinal, formation of macular hole and macular morphological changes, retinal detachment.RESULTS: BCVA was improved in both groups after 4, 8, 24wk. And the value of BCVA improvedin group B was better than that in group A(PCONCLUSION: ILM peeling combined with 38G casing needle can aspirate completely the perfluorodecalin residual on macular. There were not caused macular hole and retinal detachment. This method is an safe, effective and minimally invasive surgical technique to protect the macular function.

AIM: To observe the safety and efficacy of intravitreal injection of ranibizumab combined with laser photocoagulation for the treatment of macular edema in branch retinal vein occlusion(BRVO).METHODS: According to fundus fluorescein angiography(FFA), 30 eyes of 30 patients with BRVO were randomized into three groups: group 1(10 eyes)received grid laser treatment alone, group 2 received a single dose of intravitreal injection of ranibizumab(0.05mL/0.5mg)followed by grid laser treatment on 7d following injection, while group 3(10 eyes)received three loading doses of intravitreal ranibizumab with 0.05mL/0.5mg for three times. At 1mo interval, grid laser treatment was performed after 7d of the 1st injection. After 6mo follow-up, the best-corrected visual acuity and optical coherence tomography(OCT)and central macular thickness were observed. RESULTS:After 6mo, the visual acuity of patients were improved significantly. There was an average increase of 11 letters, 17 letters and 18 letters in group 1, 2, and 3, respectively, with the average decrease in OCT being 208.7μm, 312.9μm and 326.8μm, respectively, in these groups. Gain in visual acuity more than 3 lines was 1 case(10%)in group 1. There were 3 cases(30%)in group 2 and 4 cases(40%)in group 3.CONCLUSION:Combined therapy is better than laser therapy alone. Single dose of intravitreal ranibizumab with grid laser for macular edema in BRVO seems to be effective.

MicroRNAs can function as key tumor suppressors or oncogenes and act as biomarkers for cancer diagnosis or prognosis. Although high-throughput assays have revealed many miRNA biomarkers for pancreatic ductal adenocarcinoma (PDAC), only a few have been validated in independent populations or investigated for functional significance in PDAC pathogenesis. In this study, we correlated the expression of 36 potentially prognostic miRNAs within PDAC tissue with clinico-pathological features and survival in 151 Chinese patients. We then analyzed the functional roles and target genes of two miRNAs in PDAC development. We found that high expression of miR-186 and miR-326 predict poor and improved survival, respectively. miR-186 was over-expressed in PDAC patients compared with controls, especially in patients with large tumors (>2 cm), lymph node metastasis, or short-term survival (< 24 months). In contrast, miR-326 was down-regulated in patients compared with controls and displayed relatively increased expression in the patients with long-term survival or without venous invasion. Functional experiments revealed that PDAC cell proliferation and migration was decreased following inhibition and enhanced following over-expression of miR-186. In contrast, it was enhanced following inhibition and decreased after over-expression of miR-326. A luciferase assay indicated that miR-186 can bind directly to the 3'-UTR of NR5A2 to repress gene expression. These findings suggest that miR-186 over-expression contributes to the invasive potential of PDAC, likely via suppression of NR5A2, thereby leading to a poor prognosis; high miR-326 expression prolongs survival likely via the decreasing invasive potential of PDAC cells. These two miRNAs can be used as markers for clinical diagnosis and prognosis, and they represent therapeutic targets for PDAC.

PURPOSE:The question which kind of methods is most suitable for treating the old people for osteoporotic vertebral compression fracture is still discussed and pairwise meta-analyses cannot get hierarchies of these treatments. Our aim is to integrate the evidence to provide hierarchies of the comparative efficacy measured by the change of VAS (Visual Analogue Scale) and tolerability measured by incidence of new fractures and risk of all-cause discontinuation on three treatments (percutaneous vertebroplasty (PVP)、balloon kyphoplasty (BK) and conservative treatment (CT)). METHODS:We performed a Bayesian-framework network meta-analysis of randomized controlled trials (RCTs) to compare three treatments for the old people with osteoporotic vertebral compression fracture. The eligible RCTs were identified by searching Amed, British Nursing Index, Embase, Pubmed, the Cochrane Central Register of Controlled Trials (CENTRAL), Google scholar, SIGLE, the National Technical Information Service, the National Research Register (UK) and the Current Controlled Trials databases. Data from three outcomes (e.g. VAS, risk of all-cause discontinuation and incidence of new fractures) were independently extracted by two authors. RESULTS:A total of five RCTs were finally included into this article. PVP and BK significantly decreased VAS when compared with CT. BK had a significantly lower risk of all-cause discontinuation contrast to CT. Three treatments (BK, PVP and CT) had no significant differences in the incidence of new fractures. CONCLUSIONS:PVP may be the best way to relieve pain, CT might lead to the lowest incidence of new fractures and BK might had the lowest risk of all-cause discontinuation in old people with osteoporotic vertebral compression fracture. More large-scale and longer duration of follow-up studies are needed.

There is no prognostic model that is reliable and practical for patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). This study aimed to establish and validate a Surgery-Specific Cancer of the Liver Italian Program (SSCLIP) scoring system for those patients.668 eligible patients who underwent CLR for HCC from five separate tertiary hospitals were selected. The SSCLIP was constructed from a training cohort by adding independent predictors that were identified by Cox proportional hazards regression analyses to the original Cancer of the Liver Italian Program (CLIP). The prognostic performance of the SSCLIP at 12 and 36-months was compared with data from existing models. The patient survival distributions at different risk levels of the SSCLIP were also assessed.Four independent predictors were added to construct the SSCLIP, including age (HR = 1.075, 95%CI: 1.019-1.135, P = 0.009), albumin (HR = 0.804, 95%CI: 0.681-0.950, P = 0.011), prothrombin time activity (HR = 0.856, 95%CI: 0.751-0.975, P = 0.020) and microvascular invasion (HR = 19.852, 95%CI: 2.203-178.917, P = 0.008). In both training and validation cohorts, 12-month and 36-month prognostic performance of the SSCLIP were significantly better than those of the original CLIP, model of end-stage liver disease-based CLIP, Okuda and Child-Turcotte-Pugh score (all P < 0.05). The stratification of risk levels of the SSCLIP showed an enhanced ability to differentiate patients with different outcomes.A novel SSCLIP to predict survival of HCC patients who received CLR based on objective parameters may provide a refined, useful prognosis algorithm.

AIM: To investigate the clinical characteristics and surgical results of vireoretinal diseases in 68 patients with contralateral blindness(solitary eye). METHODS: A total of 68 patients(68 eyes)with contralateral blindness were enrolled in this retrospective consecutive study. The clinical characteristics, surgical procedures and temponade materials chosen, preoperative and postoperative visual acuity, complications and prognosis were analyzed. The follow-up ranged from 4 months to 5 years, with an average of(11.30±9.57)months. At the last follow-up, the surgical effects were evaluated.RESULTS:After operation, visual acuity increased significantly. The number of eyes with vision of 0.05 or better increased from 22 eyes(32.4%)preoperative to 60 eyes(88.2%)postoperative, and that of 0.3 or better from 3 eyes(4.4%)to 37 eyes(54.4%). The best-corrected visual acuity before and after surgery also differed significantly(t=8.986, P<0.01). CONCLUSION: With vitreoretinal surgery, visual impairment or loss due to vitreoretinal diseases can be avoided in most patients with contralateral blindness.