Exploring the induction of endometrial epithelial cell apoptosis in clinical-type endometritis in yaks through the cyt-c/caspase-3 signaling axis.

Endometritis is a significant contributor to reduced productivity in yaks in Tibet, China. The Cyt-c/Caspase-3 signaling axis plays a crucial role in the mitochondrial pathway that triggers cell apoptosis due to endogenous factors. In this study, we examined the endometrial epithelial tissue of yaks with endometritis using pathological examination, immunohistochemical analysis, TUNEL staining, qRT-PCR, and Western blot. The results indicated significant changes in the apoptotic factors of the Cyt-c/Caspase-3 signaling axis. The expression levels of Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 were significantly increased (P < 0.05), while the expression level of Bcl-2 was significantly decreased. Immunohistochemistry results revealed significant increase in Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 expression in the cytoplasm compared to the healthy group, except for Bcl-2, which showed a significant decrease. Pathological section analysis demonstrated that clinical endometritis in yaks led to structural damage, bleeding, congestion, and inflammatory cell infiltration in the endometrial epithelium. Our study findings indicated that clinical endometritis in yaks can modulate apoptosis of endometrial epithelial cells via the Cyt-c/Caspase-3 signaling pathway, resulting in different levels of damage. This research is pioneering in exploring cell apoptosis induced by clinical endometritis in yaks, offering novel insights and potential strategies for the future prevention and treatment of endometritis in yaks.

Metagenomic analysis for exploring the potential of Lactobacillus yoelii FYL1 to mitigate bacterial diarrhea and changes in the gut microbiota of juvenile yaks.

Diarrhea in calves is a common disease that results in poor nutrient absorption, poor growth and early death which leads to productivity and economic losses. Therefore, it is important to explore the methods to reduce diarrhea in yak's calves. Efficacy of lactic acid bacteria (LAB) for improvement of bacterial diarrhea is well recognized. For this purpose, two different doses (107 CFU, 1011 CFU) of Lactobacillus yoelii FYL1 isolated from yaks were fed to juvenile yaks exposed to E. coli O78. After a trial period of ten days fresh feces and intestinal contents of the experimental yaks were collected and metagenomics sequencing was performed. It was found that feeding a high dose of Lactobacillus yoelii FYL1 decreased abundance of phylum Firmicutes in the E. coli O78 infected group whereas, it was high in animals fed low dose of Lactobacillu yoelii FYL1. Results also revealed that counts of bacteria from the family Oscillospiraceae, genus Synergistes and Megasphaera were higher in control group whereas, order Bifidobacteriales and family Bifidobacteriaceae were higher in infected group. It was observed that bacterial counts for Pseudoruminococcus were significantly (P < 0.05) higher in animals of group that were given high dose of Lactobacillus yoelii FYL1 (HLAB). Compared to infected group multiple beneficial bacterial genera such as Deinococus and Clostridium were found higher in the animals that were given a low dose of Lactobacillus yoelii FYL1 (LLAB). The abundance of pathogenic bacterial genera that included Parascardovia, Bacteroides and Methanobrevibacter was decreased (P < 0.05) in the lower dose treated group. The results of functional analysis revealed that animals of LLAB had a higher metabolism of terpenoids and polyketides compared to animals of infected group. Virus annotation also presented a significant inhibitory effect of LLAB on some viruses (P < 0.05). It was concluded that L. yoelii FYL1 had an improved effect on gut microbiota of young yaks infected with E. coli O78. This experiment contributes to establish the positive effects of LAB supplementation while treating diarrhea.

Synthesis, Structural Characterization, and Biological Activities of 1,3,4- Thiadiazole Derivatives Containing Sulfonylpiperazine Structures.

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A24 demonstrated a strong efficacy with an EC50 value of 7.8 µg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 µg/mL) and bismerthiazol (43.3 µg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development.

Zinc Deficiency Exacerbates Behavioral Impediments and Dopaminergic Neuron Degeneration in a Mouse Model of Parkinson Disease.

BACKGROUND: Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD. OBJECTIVES: The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms. METHODS: Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 µg/g) or Zn deficient (ZnD; <5 µg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test. RESULTS: Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (PMPTP = 0.012, PZn = 0.014), reduced total distance traveled (PMPTP < 0.001, PZn = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (PMPTP < 0.001, PZn = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation. CONCLUSIONS: Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.

Blood levels of omega-6 fatty acids and coronary heart disease: a systematic review and metaanalysis of observational epidemiology.

Individual omega-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid (LA) and arachidonic acid (AA), may have differential impacts on cardiovascular risk. We aimed to summarize the up-to-date epidemiology evidence on the relationship between blood levels of omega-6 PUFAs and the risk of coronary heart disease (CHD). Population-based studies determining PUFA levels in blood were identified until May 2021 in PubMed, Embase, Web of Science, and Cochrane Library. Random-effects meta-analyses of cohorts comparing the highest versus lowest category were conducted to combine study-specific risk ratios (RRs) with 95% confidence intervals (CIs). Blood levels of omega-6 PUFAs were compared between the CHD case and non-case, presented as a weight mean difference (WMD). Twenty-one cohorts and eleven case-control studies were included. The WMD was -0.71 (95% CI: -1.20, -0.21) for LA and 0.08 (95% CI: -0.28, 0.43) for AA. LA levels were inversely associated with total CHD risk (RR: 0.85, 95% CI: 0.71, 1.00), but not AA. Each one-SD increase in LA levels resulted in 10% reductions in the risk of fatal CHD (RR: 0.90, 95% CI: 0.86, 0.95), but not in non-fatal CHD. Such findings highlight that the current recommendation for optimal intakes of omega-6 PUFAs (most LA) may offer a coronary benefit in primary prevention.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2056867 .

Preparation, characterization, bacteriostatic efficacy, and mechanism of zinc/selenium-loaded sodium humate.

In recent years, metal-based complexes including selenium (Se) and zinc (Zn)-containing compounds have been widely explored for their therapeutic properties due to their roles in biological processes and modulation of diverse molecular targets. Humic acid, as a metal complexing agent, is also widely used in biomedical field. In this work, three kinds of modified sodium humate (HNa), including Zn-HNA, Se-HNa, and Zn/Se-HNa, were prepared by ion exchange reaction method. The modified HNa was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and elemental mapping. The bacteriostatic activity and mechanism of modified HNa against gram-positive and gram-negative bacteria were investigated by testing bacterial inhibition zone, minimum inhibitory concentration, and capacity to destroy integrity of the bacterial membrane, promoting ROS generation level and prevention of biofilms. FTIR results showed that HNa could combine with zinc ions and selenite ions. The main XRD peaks did not change significantly. In the modified HNa, the particle shape was irregular. Compared to HNa, Zn-HNA, and Se-HNa, Zn/Se-HNa showed the strongest bacteriostatic activity. Zn/Se-HNa exhibited high bacteriostatic activity against gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae) and gram-positive bacteria (Staphylococcus aureus), but showed weak antibacterial activity against another gram-positive bacteria, Bacillus subtilis. The bacteriostasis was achieved by altering the permeability of bacterial cell membranes, generating ROS, and preventing the formation of biofilms. In conclusion, Zn/Se-HNa has high bacteriostatic activity, making it a suitable alternative to antibiotics in fields like the treatment of trauma infections and animal husbandry. KEY POINTS: • Preparate and characterize zinc- and selenium-loaded sodium humate (Zn/Se-HNa). • The combination of Zn and Se enhanced the bacteriostatic activity of HNa. • Zn/Se-HNa alters the permeability of bacterial cell membranes and promotes generation of ROS.

Design, Synthesis and Bioactivity of Novel Pyrimidine Sulfonate Esters Containing Thioether Moiety.

Pesticides play an important role in crop disease and pest control. However, their irrational use leads to the emergence of drug resistance. Therefore, it is necessary to search for new pesticide-lead compounds with new structures. We designed and synthesized 33 novel pyrimidine derivatives containing sulfonate groups and evaluated their antibacterial and insecticidal activities. Results: Most of the synthesized compounds showed good antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), Pseudomonas syringae pv. actinidiae (Psa) and Ralstonia solanacearum (Rs), and certain insecticidal activity. A5, A31 and A33 showed strong antibacterial activity against Xoo, with EC50 values of 4.24, 6.77 and 9.35 µg/mL, respectively. Compounds A1, A3, A5 and A33 showed remarkable activity against Xac (EC50 was 79.02, 82.28, 70.80 and 44.11 µg/mL, respectively). In addition, A5 could significantly improve the defense enzyme (superoxide dismutase, peroxidase, phenylalanine ammonia-lyase and catalase) activity of plants against pathogens and thus improve the disease resistance of plants. Moreover, a few compounds also showed good insecticidal activity against Plutella xylostella and Myzus persicae. The results of this study provide insight into the development of new broad-spectrum pesticides.

Field Control Effect and Initial Mechanism: A Study of Isobavachalcone against Blister Blight Disease.

Blister blight (BB) disease is caused by the obligate biotrophic fungal pathogen Exobasidium vexans Massee and seriously affects the yield and quality of Camellia sinensis. The use of chemical pesticides on tea leaves substantially increases the toxic risks of tea consumption. Botanic fungicide isobavachalcone (IBC) has the potential to control fungal diseases on many crops but has not been used on tea plants. In this study, the field control effects of IBC were evaluated by comparison and in combination with natural elicitor chitosan oligosaccharides (COSs) and the chemical pesticide pyraclostrobin (Py), and the preliminary action mode of IBC was also investigated. The bioassay results for IBC or its combination with COSs showed a remarkable control effect against BB (61.72% and 70.46%). IBC, like COSs, could improve the disease resistance of tea plants by enhancing the activity of tea-plant-related defense enzymes, including polyphenol oxidase (PPO), catalase (CAT), phenylalanine aminolase (PAL), peroxidase (POD), superoxide dismutase (SOD), ß-1,3-glucanase (Glu), and chitinase enzymes. The fungal community structure and diversity of the diseased tea leaves were examined using Illumina MiSeq sequencing of the internal transcribed spacer (ITS) region of the ribosomal rDNA genes. It was obvious that IBC could significantly alter the species' richness and the diversity of the fungal community in affected plant sites. This study broadens the application range of IBC and provides an important strategy for the control of BB disease.

Transcriptomic and Metabolomic Analysis Reveal Possible Molecular Mechanisms Regulating Tea Plant Growth Elicited by Chitosan Oligosaccharide.

Chitosan oligosaccharide (COS) plays an important role in the growth and development of tea plants. However, responses in tea plants trigged by COS have not been thoroughly investigated. In this study, we integrated transcriptomics and metabolomics analysis to understand the mechanisms of chitosan-induced tea quality improvement and growth promotion. The combined analysis revealed an obvious link between the flourishing development of the tea plant and the presence of COS. It obviously regulated the growth and development of the tea and the metabolomic process. The chlorophyll, soluble sugar, and amino acid content in the tea leaves was increased. The phytohormones, carbohydrates, and amino acid levels were zoomed-in in both transcript and metabolomics analyses compared to the control. The expression of the genes related to phytohormones transduction, carbon fixation, and amino acid metabolism during the growth and development of tea plants were significantly upregulated. Our findings indicated that alerted transcriptomic and metabolic responses occurring with the application of COS could cause efficiency in substrates in pivotal pathways and hence, elicited plant growth.

Improvement of ecosystem quality in National Key Ecological Function Zones in China during 2000-2015.

Improving ecosystem quality is the ultimate goal of ecological restoration projects and sustainable ecosystem management. However, previous results of ecosystem quality lack comparability among different regions when assessing the effectiveness of ecological restoration projects on the regional or national scales, due to the influence of geographical and climatic background conditions. Here we proposed a new index, ecosystem quality ratio (EQR), by integrating the status of landscape structure, ecosystem services, ecosystem stability, and human disturbance relative to their reference conditions, and assessed the EQR changes in China's counties and National Key Ecological Function Zones (NKEFZs) from 1990 to 2015. The results showed that the average ecosystem quality of China's counties deviated from the reference condition by 28%. EQR decreased by 1.2% during 1990-2000 but increased by 3.7% during 2000-2015. Those counties with increasing EQR in 2000-2015 occupy 64.7%, with obviously increasing counties mainly located in the water conservation, biodiversity maintenance, and water and soil conservation types of NKEFZs. The EQR increase in counties within NKEFZs was 3.65 times that outside of NKEFZs. Remarkable improvement of ecosystem quality occurred in the forest region in Changbai Mountain, biodiversity and soil conservation region in Wuling Mountains, and hilly and gully region of Loess Plateau, where EQR increases mainly resulted from the conversion of farmland to forest or grassland and consequent increases in ecosystem services and stability. The magnitude of EQR enhancement showed a positive relationship with the increase in forest and grassland coverage in NKEFZs. Our results highlight the important role of ecological restoration projects in improving ecosystem quality in China, and demonstrate the feasibility of the new index (EQR) for the assessment of ecosystem quality in terms of ecosystem management and restoration.

Alternative Splicing of TaGS3 Differentially Regulates Grain Weight and Size in Bread Wheat.

The heterotrimeric G-protein mediates growth and development by perceiving and transmitting signals in multiple organisms. Alternative splicing (AS), a vital process for regulating gene expression at the post-transcriptional level, plays a significant role in plant adaptation and evolution. Here, we identified five splicing variants of Gγ subunit gene TaGS3 (TaGS3.1 to TaGS3.5), which showed expression divergence during wheat polyploidization, and differential function in grain weight and size determination. TaGS3.1 overexpression significantly reduced grain weight by 5.89% and grain length by 5.04%, while TaGS3.2-3.4 overexpression did not significantly alter grain size compared to wild type. Overexpressing TaGS3.5 significantly increased the grain weight by 5.70% and grain length by 4.30%. Biochemical assays revealed that TaGS3 isoforms (TaGS3.1-3.4) with an intact OSR domain interact with WGB1 to form active Gßγ heterodimers that further interact with WGA1 to form inactive Gαßγ heterotrimers. Truncated isoforms TaGS3.2-3.4 , which lack the C-terminal Cys-rich region but have enhanced binding affinity to WGB1, antagonistically compete with TaGS3.1 to bind WGB1, while TaGS3.5 with an incomplete OSR domain does not interact with WGB1. Taking these observations together, we proposed that TaGS3 differentially regulates grain size via AS, providing a strategy by which the grain size is fine-tuned and regulated at the post-transcriptional level.

FOXA1-induced circOSBPL10 potentiates cervical cancer cell proliferation and migration through miR-1179/UBE2Q1 axis.

BACKGROUND: Recently, extensive evidence has clarified the crucial role of circular RNAs (circRNAs) as a pro-tumor or anti-cancer participant in human malignancies. A new circRNA derived from oxysterol binding protein like 10 (OSBPL10) (circOSBPL10) has not been researched in cervical cancer (CC) yet. METHODS: The expression of molecules was analyzed by RT-qPCR or western blot. Several functional assays were applied to explore the biological influence of circOSBPL10 on CC. The interaction between RNAs was estimated via luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. RESULTS: CircOSBPL10 characterized with cyclic structure was revealed to possess elevated expression in CC cells. CircOSBPL10 downregulation elicited suppressive impacts on CC cell proliferation and migration. Interestingly, circOSBPL10 regulated CC progression by interacting with microRNA-1179 (miR-1179). Moreover, ubiquitin conjugating enzyme E2 Q1 (UBE2Q1) targeted by miR-1179 was positively regulated by circOSBPL10 in CC. Furthermore, enhanced UBE2Q1 expression or suppressed miR-1179 level countervailed the repressive effect of circOSBPL10 depletion on the malignant phenotypes of CC cells. Moreover, forkhead box A1 (FOXA1) was confirmed to induce circOSBPL10 expression in CC cells. CONCLUSIONS: FOXA1-induced circOSBPL10 facilitates CC progression through miR-1179/UBE2Q1 axis, highlighting a strong potential for circOSBPL10 to serve as a promising therapeutic target in CC.

Underestimated ecosystem carbon turnover time and sequestration under the steady state assumption: A perspective from long-term data assimilation.

It is critical to accurately estimate carbon (C) turnover time as it dominates the uncertainty in ecosystem C sinks and their response to future climate change. In the absence of direct observations of ecosystem C losses, C turnover times are commonly estimated under the steady state assumption (SSA), which has been applied across a large range of temporal and spatial scales including many at which the validity of the assumption is likely to be violated. However, the errors associated with improperly applying SSA to estimate C turnover time and its covariance with climate as well as ecosystem C sequestrations have yet to be fully quantified. Here, we developed a novel model-data fusion framework and systematically analyzed the SSA-induced biases using time-series data collected from 10 permanent forest plots in the eastern China monsoon region. The results showed that (a) the SSA significantly underestimated mean turnover times (MTTs) by 29%, thereby leading to a 4.83-fold underestimation of the net ecosystem productivity (NEP) in these forest ecosystems, a major C sink globally; (b) the SSA-induced bias in MTT and NEP correlates negatively with forest age, which provides a significant caveat for applying the SSA to young-aged ecosystems; and (c) the sensitivity of MTT to temperature and precipitation was 22% and 42% lower, respectively, under the SSA. Thus, under the expected climate change, spatiotemporal changes in MTT are likely to be underestimated, thereby resulting in large errors in the variability of predicted global NEP. With the development of observation technology and the accumulation of spatiotemporal data, we suggest estimating MTTs at the disequilibrium state via long-term data assimilation, thereby effectively reducing the uncertainty in ecosystem C sequestration estimations and providing a better understanding of regional or global C cycle dynamics and C-climate feedback.

Irinotecan-platinum combination therapy for previously untreated extensive-stage small cell lung cancer patients: a meta-analysis.

BACKGROUND: There is still a debate regarding whether regimens combining irinotecan with platinum could replace regimens combining etoposide with platinum, as first-line chemotherapy for extensive-stage small cell lung cancer (ES-SCLC). We performed a meta-analysis to compare these regimens as first-line chemotherapy for ES-SCLC. METHODS: A literature search for randomized controlled trials was performed using the Cochrane Library, PubMed, and Embase. The inverse variance method was used to estimate summary hazard ratios and their 95% confidence intervals for overall survival and progression free survival. Relative risk was used to estimate the overall response rate, disease control rate, 1-year survival, 2-year survival, and adverse event data. RESULT: Nine randomized controlled trials (2451 patients) were included. Regimens combining irinotecan and platinum improved overall survival, progression-free survival and overall response rate compared to combination etoposide and platinum regimens. Meanwhile, superior progression-free survival and overall response rate outcomes were observed in the Asian subgroup of patients. These patients receiving a combination irinotecan and platinum regimen experienced grade 3-4 diarrhea more frequently and experienced less hematologic toxic events than the non-Asian groups. CONCLUSIONS: Our data suggest that a combination irinotecan and platinum regimen can prolong overall survival, progression-free survival and overall response rate for patients with ES-SCLC as compared to a combination etoposide and platinum regimen. And the Asian patients could benefit from irinotecan combined with platinum easier.

Induced Resistance Mechanism of Novel Curcumin Analogs Bearing a Quinazoline Moiety to Plant Virus.

Plant immune activators can protect crops from plant virus pathogens by activating intrinsic immune mechanisms in plants and are widely used in agricultural production. In our previous work, we found that curcumin analogs exhibit excellent biological activity against plant viruses, especially protective activity. Inspired by these results, the active substructure of pentadienone and quinazoline were spliced to obtain curcumin analogs as potential exogenously induced resistant molecule. Bioassay results showed that compound A13 exhibited excellent protective activity for tobacco to against Tobacco mosaic virus (TMV) at 500 µg/mL, with a value of 70.4 ± 2.6% compared with control treatments, which was better than that of the plant immune activator chitosan oligosaccharide (49.0 ± 5.9%). The protective activity is due to compound A13 inducing tobacco resistance to TMV, which was related to defense-related enzymes, defense-related genes, and photosynthesis. This was confirmed by the up-regulated expression of proteins that mediate stress responses and oxidative phosphorylation.

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.

Effects of ABCDE Bundle on Hemodynamics in Patients on Mechanical Ventilation.

BACKGROUND Mechanical ventilation is an important part of advanced life support in the intensive care unit (ICU). This study aimed to investigate the effects of ABCDE bundle on hemodynamics in patients on mechanical ventilation (MV). MATERIAL AND METHODS This study used a cross-sectional overall controlled approach in which 143 patients on mechanical ventilation were divided into 2 groups. In the pre-ABCDE bundle group (n=70), conventional sedation and analgesia strategy were used. In the post-ABCDE bundle group (n=73), ABCDE bundle was used. Changes in hemodynamics parameters and related prognostic indicators were monitored at various time points before (T0) and at 1 d (T1), 3 d (T3), 5 d (T5), and 7 d (T7) after implementation of the 2 strategies. RESULTS Mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), and oxygenation index (PaO2/FiO2) in the bundle group were improved more significantly than those in the pre-ABCDE bundle group (P<0.05). For comparison between various monitoring time points in the same group, compared with before intervention, MAP, CVP, HR, and PaO2/FiO2 changed significantly in the bundle group at 3 d, 5 d, and 7 d after intervention, and the difference was statistically significant (P<0.05). Compared with before intervention, differences in all hemodynamics indicators were statistically significant in the pre-ABCDE bundle group at 5 d and 7 d after intervention (P<0.05). Compared with the pre-ABCDE bundle group, differences in prognostic indicators in the post-ABCDE bundle were statistically significant (P<0.05). CONCLUSIONS ABCDE bundle is safe and effective for patients on mechanical ventilation, and can improve hemodynamics and enhance oxygenation index. ABCDE bundle might be helpful in reducing 28-d mortality and improving prognosis.

[Intelligent watch system for health monitoring based on Bluetooth low energy technology].

According to the development status of wearable technology and the demand of intelligent health monitoring, we studied the multi-function integrated smart watches solution and its key technology. First of all, the sensor technology with high integration density, Bluetooth low energy (BLE) and mobile communication technology were integrated and used in develop practice. Secondly, for the hardware design of the system in this paper, we chose the scheme with high integration density and cost-effective computer modules and chips. Thirdly, we used real-time operating system FreeRTOS to develop the friendly graphical interface interacting with touch screen. At last, the high-performance application software which connected with BLE hardware wirelessly and synchronized data was developed based on android system. The function of this system included real-time calendar clock, telephone message, address book management, step-counting, heart rate and sleep quality monitoring and so on. Experiments showed that the collecting data accuracy of various sensors, system data transmission capacity, the overall power consumption satisfy the production standard. Moreover, the system run stably with low power consumption, which could realize intelligent health monitoring effectively.

Formin-like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer.

Formin-like2 (FMNL2) is a member of the diaphanous-related formins family, which act as effectors and upstream modulators of Rho GTPases signaling and control the actin-dependent processes, such as cell motility or invasion. FMNL2 has been identified as promoting the motility and metastasis in colorectal carcinoma (CRC). However, whether FMNL2 regulates Rho signaling to promote cancer cell invasion remains unclear. In this study, we demonstrated an essential role for FMNL2 in the activations of Rho/ROCK pathway, SRF transcription or actin assembly, and subsequent CRC cell invasion. FMNL2 could activate Rho/ROCK pathway, and required ROCK to promote CRC cell invasion. Moreover, FMNL2 promoted the formation of filopodia and stress fiber, and activated the SRF transcription in a Rho-dependent manner. We also demonstrated that FMNL2 was necessary for LPA-induced invasion, RhoA/ROCK activation, actin assembly and SRF activation. FMNL2 was an essential component of LPA signal transduction toward RhoA by directly interacting with LARG. LARG silence inhibited RhoA/ROCK pathway and CRC cell invasion. Collectively, these data indicate that FMNL2, acting as upstream of RhoA by interacting with LARG, can promote actin assembly and CRC cell invasion through a Rho/ROCK-dependent mechanism.

MicroRNA-34a targets FMNL2 and E2F5 and suppresses the progression of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies. Increasing evidences indicate that dysregulation of miRNAs is a frequent event in CRC and contributes to the pathogenesis of CRC. In this study, we found that over-expression of miR-34a inhibited cell proliferation and invasion, induced a cell cycle arrest and triggered apoptosis, while knockdown of miR-34a showed the opposite effects. Moreover, ectopic miR-34a suppressed tumor growth and metastasis of CRC cells in vivo. FMNL2 and E2F5 were identified as direct targets of miR-34a. Reintroduction of FMNL2 or E2F5 without 3'UTR region reversed the inhibitory effects of miR-34a on cell proliferation and invasion. MiR-34a was down-regulated in CRC cells and inversely correlated with FMNL2 and E2F5 expressions. Our study suggests that miR-34a is an important tumor suppressor of CRC progression by targeting FMNL2 and E2F5, thus providing new insight into the molecular mechanisms underlying CRC progression and establishing a strong potential for the application of miR-34a as a novel therapeutic marker against CRC.